Prospective Cohort Study of Enterotoxigenic Escherichia coli Infections in Argentinean Children

PubMed Central

Viboud, Gloria I.; Jouve, Mabel J.; Binsztein, Norma; Vergara, Marta; Rivas, Marta; Quiroga, Marina; Svennerholm, Ann-Mari

1999-01-01

In a follow-up study, enterotoxigenic Escherichia coli (ETEC) infections in 145 children from two communities located in northeastern Argentina were monitored for 2 years. The occurrence of diarrhea was monitored by weekly household visits. Of 730 fecal specimens collected, 137 (19%) corresponded to diarrheal episodes. ETEC was isolated from a significantly higher proportion of symptomatic (18.3%) than asymptomatic (13.3%) children (P = 0.04541). Individuals of up to 24 months of age were found to have a higher risk of developing ETEC diarrhea than older children (odds ratio [OR], 3.872; P = 0.00021). When the toxin profiles were considered, only heat stable enterotoxin (ST)-producing ETEC was directly associated with diarrhea (P = 0.00035). Fifty-five percent of the ETEC isolated from symptomatic children and 19% of the ETEC isolated from asymptomatic children expressed one of the colonization factors (CFs) investigated, i.e., CF antigen I (CFA/I), CFA/II, CFA/III, and CFA/IV; coli surface antigens CS7 and CS17; and putative CFs PCFO159, PCFO166, and PCFO20, indicating a clear association between diarrhea and ETEC strains that carry these factors (P = 0.0000034). The most frequently identified CFs were CFA/IV (16%), CFA/I (10%), and CS17 (9%). CFs were mostly associated with ETEC strains that produce ST and both heat-labile enterotoxin and ST. Logistic regression analysis, applied to remove confounding effects, revealed that the expression of CFs was associated with illness independently of the toxin type (OR, 4.81; P = 0.0003). When each CF was considered separately, CS17 was the only factor independently associated with illness (OR, 16.6; P = 0.0151). Most CFs (the exception was CFA/IV) fell within a limited array of serotypes, while the CF-negative isolates belonged to many different O:H types. These results demonstrate that some CFs are risk factors for the development of ETEC diarrhea. PMID:10449460

Chaperone-Usher Pili Loci of Colonization Factor-Negative Human Enterotoxigenic Escherichia coli

PubMed Central

Del Canto, Felipe; O'Ryan, Miguel; Pardo, Mirka; Torres, Alexia; Gutiérrez, Daniela; Cádiz, Leandro; Valdés, Raul; Mansilla, Aquiles; Martínez, Rodrigo; Hernández, Daniela; Caro, Benjamin; Levine, Myron M.; Rasko, David A.; Hill, Christopher M.; Pop, Mihai; Stine, O. Colin; Vidal, Roberto

2017-01-01

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea worldwide. Among the 25 different ETEC adhesins, 22 are known as “colonization factors” (CFs), of which 17 are assembled by the chaperone-usher (CU) mechanism. Currently, there is no preventive therapy against ETEC, and CFs have been proposed as components for vaccine development. However, studies of diarrhea-causing ETEC strains worldwide indicate that between 15 and 50% of these are negative for known CFs, hindering the selection of the most widespread structures and suggesting that unknown adhesins remain to be identified. Here, we report the result of a comprehensive analysis of 35 draft genomes of ETEC strains which do not carry known adhesin genes; our goal was to find new CU pili loci. The phylogenetic profiles and serogroups of these strains were highly diverse, a majority of which produced only the heat-labile toxin. We identified 10 pili loci belonging to CU families β (1 locus), γ2 (7 loci), κ (1 locus), and π (1 locus), all of which contained the required number of open reading frames (ORFs) to encode functional structures. Three loci were variants of previously-known clusters, three had been only-partially described, and four are novel loci. Intra-loci genetic variability identified would allow the synthesis of up to 14 different structures. Clusters of putative γ2-CU pili were most common (23 strains), followed by putative β-CU pili (12 strains), which have not yet been fully characterized. Overall, our findings significantly increase the number of ETEC adhesion genes associated with human infections. PMID:28111618

A food-grade fimbrial adhesin FaeG expression system in Lactococcus lactis and Lactobacillus casei.

PubMed

Lu, W W; Wang, T; Wang, Y; Xin, M; Kong, J

2016-03-01

Enterotoxigenic Escherichia coli (ETEC) infection is the major cause of diarrhea in neonatal piglets. The fimbriae as colonizing factor in the pathogenesis of ETEC constitute a primary target for vaccination against ETEC. Lactic acid bacteria (LAB) are attractive tools to deliver antigens at the mucosal level. With the safety of genetically modified LAB in mind, a food-grade secretion vector (pALRc or pALRb) was constructed with DNA entirely from LAB, including the replicon, promoter, signal peptide, and selection marker alanine racemase gene (alr). To evaluate the feasibility of the system, the nuclease gene (nuc) from Staphylococcus aureus was used as a reporter to be expressed in both Lactococcus lactis and Lactobacillus casei. Subsequently, the extracellular secretion of the fimbrial adhesin FaeG of ETEC was confirmed by Western blot analysis. These results showed that this food-grade expression system has potential as the delivery vehicle for the safe use of genetically modified LAB for the development of vaccines against ETEC infection.

Genotypic and Phenotypic Characterization of Enterotoxigenic Escherichia coli Strains Isolated from Peruvian Children ▿

PubMed Central

Rivera, F. P.; Ochoa, T. J.; Maves, R. C.; Bernal, M.; Medina, A. M.; Meza, R.; Barletta, F.; Mercado, E.; Ecker, L.; Gil, A. I.; Hall, E. R.; Huicho, L.; Lanata, C. F.

2010-01-01

Enterotoxigenic Escherichia coli (ETEC) is a major cause of childhood diarrhea. The present study sought to determine the prevalence and distribution of toxin types, colonization factors (CFs), and antimicrobial susceptibility of ETEC strains isolated from Peruvian children. We analyzed ETEC strains isolated from Peruvian children between 2 and 24 months of age in a passive surveillance study. Five E. coli colonies per patient were studied by multiplex real-time PCR to identify ETEC virulence factors. ETEC-associated toxins were confirmed using a GM1-based enzyme-linked immunosorbent assay. Confirmed strains were tested for CFs by dot blot assay using 21 monoclonal antibodies. We analyzed 1,129 samples from children with diarrhea and 744 control children and found ETEC in 5.3% and 4.3%, respectively. ETEC was more frequently isolated from children >12 months of age than from children <12 months of age (P < 0.001). Fifty-two percent of ETEC isolates from children with diarrhea and 72% of isolates from controls were heat-labile enterotoxin (LT) positive and heat-stable enterotoxin (ST) negative; 25% and 19%, respectively, were LT negative and ST positive; and 23% and 9%, respectively, were LT positive and ST positive. CFs were identified in 64% of diarrheal samples and 37% of control samples (P < 0.05). The most common CFs were CS6 (14% and 7%, respectively), CS12 (12% and 4%, respectively), and CS1 (9% and 4%, respectively). ST-producing ETEC strains caused more severe diarrhea than non-ST-producing ETEC strains. The strains were most frequently resistant to ampicillin (71%) and co-trimoxazole (61%). ETEC was thus found to be more prevalent in older infants. LT was the most common toxin type; 64% of strains had an identified CF. These data are relevant in estimating the burden of disease due to ETEC and the potential coverage of children in Peru by investigational vaccines. PMID:20631096

Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea

PubMed Central

Sack, David A.

2015-01-01

Diarrhea continues to be a leading cause of death in children <5 years of age, and enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of children's diarrhea. Currently, there are no available vaccines against ETEC-associated diarrhea. Whole-cell vaccine candidates have been under development but require further improvements because they provide inadequate protection and produce unwanted adverse effects. Meanwhile, a newer approach using polypeptide or subunit vaccine candidates focusing on ETEC colonization factor antigens (CFAs) and enterotoxins, the major virulence determinants of ETEC diarrhea, shows substantial promise. A conservative CFA/I adhesin tip antigen and a CFA MEFA (multiepitope fusion antigen) were shown to induce cross-reactive antiadhesin antibodies that protected against adherence by multiple important CFAs. Genetic fusion of toxoids derived from ETEC heat-labile toxin (LT) and heat-stable toxin (STa) induced antibodies neutralizing both enterotoxins. Moreover, CFA-toxoid MEFA polypeptides, generated by fusing CFA MEFA to an STa-LT toxoid fusion, induced antiadhesin antibodies that broadly inhibited adherence of the seven most important ETEC CFAs associated with about 80% of the diarrhea cases caused by ETEC strains with known CFAs. This same antigen preparation also induced antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea. Results from these studies suggest that polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. In addition, novel adhesins and mucin proteases have been investigated as potential alternatives or, more likely, additional antigens for ETEC subunit vaccine development. PMID:26135975

Distribution of Classical and Nonclassical Virulence Genes in Enterotoxigenic Escherichia coli Isolates from Chilean Children and tRNA Gene Screening for Putative Insertion Sites for Genomic Islands▿†

PubMed Central

Del Canto, Felipe; Valenzuela, Patricio; Cantero, Lidia; Bronstein, Jonathan; Blanco, Jesús E.; Blanco, Jorge; Prado, Valeria; Levine, Myron; Nataro, James; Sommerfelt, Halvor; Vidal, Roberto

2011-01-01

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea. Three adhesins (Tia, TibA, EtpA), an iron acquisition system (Irp1, Irp2, and FyuA), a GTPase (LeoA), and an autotransporter (EatA) are ETEC virulence-related proteins that, in contrast to the classical virulence factors (enterotoxins and fimbrial colonization factors) have not heretofore been targets in characterizing isolates from epidemiological studies. Here, we determined the occurrence of these nonclassical virulence genes in 103 ETEC isolates from Chilean children with diarrhea and described their association with O serogroups and classical virulence determinants. Because tia, leoA, irp2, and fyuA are harbored by pathogenicity islands inserted into the selC and asnT tRNA genes (tDNAs), we analyzed the regions flanking these loci. Ten additional tDNAs were also screened to identify hot spots for genetic insertions. Associations between the most frequent serogroups and classical colonization factor (CF)-toxin profiles included O6/LT-STh/CS1-CS3-CS21 (i.e., O6 serogroup, heat-labile [LT] and human heat-stable [STh] enterotoxins, and CFs CS1, -3 and -21), O6/LT-STh/CS2-CS3-CS21, and O104-O127/STh/CFAI-CS21. The eatA and etpA genes were detected in more than 70% of the collection, including diverse serogroups and virulence profiles. Sixteen percent of the ETEC strains were negative for classical and nonclassical adhesins, suggesting the presence of unknown determinants of adhesion. The leuX, thrW, and asnT tDNAs were disrupted in more than 65% of strains, suggesting they are hot spots for the insertion of mobile elements. Sequences similar to integrase genes were identified next to the thrW, asnT, pheV, and selC tDNAs. We propose that the eatA and etpA genes should be included in characterizations of ETEC isolates in future epidemiological studies to determine their prevalence in other geographical regions. Sequencing of tDNA-associated genetic insertions might identify new ETEC virulence determinants. PMID:21775541

Randomised, double-blind, safety and efficacy of a killed oral vaccine for enterotoxigenic E. Coli diarrhoea of travellers to Guatemala and Mexico.

PubMed

Sack, David A; Shimko, Janet; Torres, Olga; Bourgeois, August L; Francia, Domingo Sanchez; Gustafsson, Björn; Kärnell, Anders; Nyquist, Iréne; Svennerholm, Ann-Mari

2007-05-30

We tested the efficacy of a killed oral vaccine for enterotoxigenic Escherichia coli (ETEC) diarrhoea to determine if two doses of vaccine with colonization factor antigens (CF) and cholera B subunit would protect against ETEC diarrhoea of travellers. Six hundred seventy-two healthy travellers going to Mexico or Guatemala were studied in a prospective, randomised, placebo-controlled trial. The primary outcome was a vaccine preventable outcome (VPO), defined as an episode of ETEC diarrhoea with an ETEC organism producing heat labile toxin (LT) or CF homologous with the vaccine, without other known causes. The vaccine was safe and stimulated anti-heat labile toxin antibodies. There was a significant decrease in more severe VPO episodes (PE=77%, p=0.039) as defined by symptoms that interfered with daily activities or more than five loose stools in a day, although the total number of VPO events did not differ significantly in the vaccine and placebo groups. We conclude that the new oral ETEC vaccine reduces the rate of more severe episodes of traveller's diarrhoea (TD) due to VPO-ETEC, but it did not reduce the overall rate of ETEC diarrhoea or of travellers' diarrhoea due to other causes.

ANIMAL ENTEROTOXIGENIC ESCHERICHIA COLI

PubMed Central

Dubreuil, J. Daniel; Isaacson, Richard E.; Schifferli, Dieter M.

2016-01-01

Enterotoxigenic Escherichia coli (ETEC) is the most common cause of E. coli diarrhea in farm animals. ETEC are characterized by the ability to produce two types of virulence factors; adhesins that promote binding to specific enterocyte receptors for intestinal colonization and enterotoxins responsible for fluid secretion. The best-characterized adhesins are expressed in the context of fimbriae, such as the F4 (also designated K88), F5 (K99), F6 (987P), F17 and F18 fimbriae. Once established in the animal small intestine, ETEC produces enterotoxin(s) that lead to diarrhea. The enterotoxins belong to two major classes; heat-labile toxin that consist of one active and five binding subunits (LT), and heat-stable toxins that are small polypeptides (STa, STb, and EAST1). This chapter describes the disease and pathogenesis of animal ETEC, the corresponding virulence genes and protein products of these bacteria, their regulation and targets in animal hosts, as well as mechanisms of action. Furthermore, vaccines, inhibitors, probiotics and the identification of potential new targets identified by genomics are presented in the context of animal ETEC. PMID:27735786

Enterotoxigenic Escherichia coli blood group A interactions intensify diarrheal severity.

PubMed

Kumar, Pardeep; Kuhlmann, F Matthew; Chakroborty, Subhra; Bourgeois, A Louis; Foulke-Abel, Jennifer; Tumala, Brunda; Vickers, Tim J; Sack, David A; DeNearing, Barbara; Harro, Clayton D; Wright, W Shea; Gildersleeve, Jeffrey C; Ciorba, Matthew A; Santhanam, Srikanth; Porter, Chad K; Gutierrez, Ramiro L; Prouty, Michael G; Riddle, Mark S; Polino, Alexander; Sheikh, Alaullah; Donowitz, Mark; Fleckenstein, James M

2018-05-17

Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, that may involve strain-specific virulence features as well as host factors, have not been elucidated. We demonstrate that when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups. Interestingly, a diverse population of ETEC strains, including H10407, secrete a novel adhesin molecule, EtpA. As many bacterial adhesins also agglutinate red blood cells, we combined the use of glycan arrays, biolayer inferometry, and non-canonical amino acid labeling with hemagglutination studies to demonstrate that EtpA is a dominant ETEC blood group A specific lectin/hemagglutinin. Importantly, we also show that EtpA interacts specifically with glycans expressed on intestinal epithelial cells from blood group A individuals, and that EtpA-mediated bacterial-host interactions accelerate bacterial adhesion and the effective delivery both heat-labile and heat-stable toxins of ETEC. Collectively, these data provide additional insight into the complex molecular basis of severe ETEC diarrheal illness that may inform rational design of vaccines to protect those at highest risk.

A Role for Salivary Peptides in the Innate Defense Against Enterotoxigenic Escherichia coli.

PubMed

Brown, Jeffrey W; Badahdah, Arwa; Iticovici, Micah; Vickers, Tim J; Alvarado, David M; Helmerhorst, Eva J; Oppenheim, Frank G; Mills, Jason C; Ciorba, Matthew A; Fleckenstein, James M; Bullitt, Esther

2018-04-11

Diarrheal disease from enterotoxigenic Escherichia coli (ETEC) causes significant worldwide morbidity and mortality in young children residing in endemic countries and is the leading cause of traveler's diarrhea. As ETEC enters the body through the oral cavity and cotransits the digestive tract with salivary components, we hypothesized that the antimicrobial activity of salivary proteins might extend beyond the oropharynx into the proximal digestive tract. Here, we show that the salivary peptide histatin-5 binds colonization factor antigen I pili, thereby blocking adhesion of ETEC to intestinal epithelial cells. Mechanistically, we demonstrate that histatin-5 stiffens the typically dynamic pili, abolishing their ability to function as spring-like shock absorbers, thereby inhibiting colonization within the turbulent vortices of chyme in the gastrointestinal tract. Our data represent the first report of a salivary component exerting specific antimicrobial activity against an enteric pathogen and suggest that histatin-5 and related peptides might be exploited for prophylactic and/or therapeutic uses. Numerous viruses, bacteria, and fungi traverse the oropharynx to cause disease, so there is considerable opportunity for various salivary components to neutralize these pathogens prior to arrival at their target organ. Identification of additional salivary components with unexpectedly broad antimicrobial spectra should be a priority.

Biofilm formation and binding specificities of CFA/I, CFA/II and CS2 adhesions of enterotoxigenic Escherichia coli and Cfae-R181A mutant.

PubMed

Liaqat, Iram; Sakellaris, Harry

2012-07-01

Enterotoxigenic Escherichia coli (ETEC) strains are leading causes of childhood diarrhea in developing countries. Adhesion is the first step in pathogenesis of ETEC infections and ETEC pili designated colonization factor antigens (CFAs) are believed to be important in the biofim formation, colonization and host cell adhesions. As a first step, we have determined the biofilm capability of ETEC expressing various types of pili (CFA/I, CfaE-R181A mutant/CfaE tip mutant, CFA/II and CS2). Further, enzyme-linked immunosorbent assay (ELISA) assay were developed to compare the binding specificity of CFA/I, CFA/II (CS1 - CS3) and CS2 of ETEC, using extracted pili and piliated bacteria. CFA/II strain (E24377a) as well as extracted pili exhibited significantly higher binding both in biofilm and ELISA assays compared to non piliated wild type E24377a, CFA/I and CS2 strains. This indicates that co-expression of two or more CS2 in same strain is more efficient in increasing adherence. Significant decrease in binding specificity of DH5αF'lacI (q)/∆cotD (CS2) strain and MC4100/pEU2124 (CfaE-R181A) mutant strain indicated the important contribution of tip proteins in adherence assays. However, CS2 tip mutant strain (DH5αF'lacI (q)/pEU5881) showed that this specific residue may not be important as adhesions in these strains. In summary, our data suggest that pili, their minor subunits are important for biofilm formation and adherence mechanisms. Overall, the functional reactivity of strains co expressing various antigens, particularly minor subunit antigen observed in this study suggest that fewer antibodies may be required to elicit immunity to ETEC expressing a wider array of related pili.

Molecular Characterization of Enterotoxigenic Escherichia coli Isolates Recovered from Children with Diarrhea during a 4-Year Period (2007 to 2010) in Bolivia

PubMed Central

Gonzales, Lucia; Sanchez, Samanta; Zambrana, Silvia; Wiklund, Gudrun; Svennerholm, Ann-Mari

2013-01-01

Enterotoxigenic Escherichia coli (ETEC) is an important cause of childhood diarrhea. This study aimed to characterize ETEC strains isolated from Bolivian children aged <5 years according to enterotoxin profile, colonization factors (CFs), suggested virulence genes, and severity of disease. A total of 299 ETEC isolates recovered from children with diarrhea and 55 ETEC isolates from children without diarrhea (controls) were isolated over a period of 4 years. Strains expressing heat-labile toxin (LT) or heat-stable toxin (ST) alone were about equally common and twice as common as ETEC producing both toxins (20%). ETEC strains expressing human ST (STh) were more common in children aged <2 years, while ETEC strains expressing LT plus STh (LT/STh) were more frequent in 2- to 5-year-old children. Severity of disease was not related to the toxin profile of the strains. CF-positive isolates were more frequently identified in diarrheal samples than in control samples (P = 0.02). The most common CFs were CFA/I and CS14. CFA/I ETEC strains were more frequent in children aged <2 years than CS1+CS3 isolates and CS14 isolates, which were more prevalent in 2- to 5-year-old children. The presence of suggested ETEC virulence genes (clyA, eatA, tia, tibC, leoA, and east-1) was not associated with disease. However, east-1 was associated with LT/STh strains (P < 0.001), eatA with STh strains (P < 0.001), and tia with LT/STh strains (P < 0.001). A minor seasonal peak of ETEC infections was identified in May during the cold-dry season and coincided with the peak of rotavirus infections; this pattern is unusual for ETEC and may be important for vaccination strategies in Bolivia. PMID:23390275

Enterotoxigenic Escherichia coli Elicits Immune Responses to Multiple Surface Proteins▿ †

PubMed Central

Roy, Koushik; Bartels, Scott; Qadri, Firdausi; Fleckenstein, James M.

2010-01-01

Enterotoxigenic Escherichia coli (ETEC) causes considerable morbidity and mortality due to diarrheal illness in developing countries, particularly in young children. Despite the global importance of these heterogeneous pathogens, a broadly protective vaccine is not yet available. While much is known regarding the immunology of well-characterized virulence proteins, in particular the heat-labile toxin (LT) and colonization factors (CFs), to date, evaluation of the immune response to other antigens has been limited. However, the availability of genomic DNA sequences for ETEC strains coupled with proteomics technology affords opportunities to examine novel uncharacterized antigens that might also serve as targets for vaccine development. Analysis of whole or fractionated bacterial proteomes with convalescent-phase sera can potentially accelerate identification of secreted or surface-expressed targets that are recognized during the course of infection. Here we report results of an immunoproteomics approach to antigen discovery with ETEC strain H10407. Immunoblotting of proteins separated by two-dimensional electrophoresis (2DE) with sera from mice infected with strain H10407 or with convalescent human sera obtained following natural ETEC infections demonstrated multiple immunoreactive molecules in culture supernatant, outer membrane, and outer membrane vesicle preparations, suggesting that many antigens are recognized during the course of infection. Proteins identified by this approach included established virulence determinants, more recently identified putative virulence factors, as well as novel secreted and outer membrane proteins. Together, these studies suggest that existing and emerging proteomics technologies can provide a useful complement to ongoing approaches to ETEC vaccine development. PMID:20457787

Oral Administration of a Select Mixture of Bacillus Probiotics Affects the Gut Microbiota and Goblet Cell Function following Escherichia coli Challenge in Newly Weaned Pigs of Genotype MUC4 That Are Supposed To Be Enterotoxigenic E. coli F4ab/ac Receptor Negative.

PubMed

Zhang, Wei; Zhu, Yao-Hong; Zhou, Dong; Wu, Qiong; Song, Dan; Dicksved, Johan; Wang, Jiu-Feng

2017-02-01

Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. Low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to piglets of genotype MUC4 that are supposed to be F4-expressing enterotoxigenic Escherichia coli strain (F4 + ETEC) F4ab/ac receptor negative (i.e., MUC4-resistant piglets) for 1 week before F4 + ETEC challenge. The luminal contents were collected from the mucosa of the colon on day 8 after F4 + ETEC challenge. The BLS mix attenuated E. coli-induced expansion of Bacteroides uniformis, Eubacterium eligens, Acetanaerobacterium, and Sporobacter populations. Clostridium and Turicibacter populations increased following F4 + ETEC challenge in pigs pretreated with low-dose BLS mix. Lactobacillus gasseri and Lactobacillus salivarius populations increased after administration of BLS mix during E. coli infection. The beneficial effects of BLS mix were due in part to the expansion of certain Clostridium, Lactobacillus, and Turicibacter populations, with a corresponding increase in the number of goblet cells in the ileum via upregulated Atoh1 expression, in turn increasing MUC2 production and thus preserving the mucus barrier and enhancing host defenses against enteropathogenic bacteria. However, excessive BLS mix consumption may increase the risk for enteritis, partly through disruption of colonic microbial ecology, characterized by expansion of Proteobacteria and impaired goblet cell function in the ileum. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. The present study is important for improving our understanding of the protective role of probiotics against Escherichia coli infection in piglets. Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. In this study, low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to MUC4-resistant piglets for 1 week before the F4-expressing ETEC strain (F4 + ETEC) challenge. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. Copyright © 2017 American Society for Microbiology.

Oral Administration of a Select Mixture of Bacillus Probiotics Affects the Gut Microbiota and Goblet Cell Function following Escherichia coli Challenge in Newly Weaned Pigs of Genotype MUC4 That Are Supposed To Be Enterotoxigenic E. coli F4ab/ac Receptor Negative

PubMed Central

Zhang, Wei; Zhou, Dong; Wu, Qiong; Song, Dan; Dicksved, Johan; Wang, Jiu-Feng

2016-01-01

ABSTRACT Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. Low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to piglets of genotype MUC4 that are supposed to be F4-expressing enterotoxigenic Escherichia coli strain (F4+ ETEC) F4ab/ac receptor negative (i.e., MUC4-resistant piglets) for 1 week before F4+ ETEC challenge. The luminal contents were collected from the mucosa of the colon on day 8 after F4+ ETEC challenge. The BLS mix attenuated E. coli-induced expansion of Bacteroides uniformis, Eubacterium eligens, Acetanaerobacterium, and Sporobacter populations. Clostridium and Turicibacter populations increased following F4+ ETEC challenge in pigs pretreated with low-dose BLS mix. Lactobacillus gasseri and Lactobacillus salivarius populations increased after administration of BLS mix during E. coli infection. The beneficial effects of BLS mix were due in part to the expansion of certain Clostridium, Lactobacillus, and Turicibacter populations, with a corresponding increase in the number of goblet cells in the ileum via upregulated Atoh1 expression, in turn increasing MUC2 production and thus preserving the mucus barrier and enhancing host defenses against enteropathogenic bacteria. However, excessive BLS mix consumption may increase the risk for enteritis, partly through disruption of colonic microbial ecology, characterized by expansion of Proteobacteria and impaired goblet cell function in the ileum. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. IMPORTANCE The present study is important for improving our understanding of the protective role of probiotics against Escherichia coli infection in piglets. Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. In this study, low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to MUC4-resistant piglets for 1 week before the F4-expressing ETEC strain (F4+ ETEC) challenge. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. PMID:27881419

Clinical trial to evaluate safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli prototype vaccine containing CFA/I overexpressing bacteria and recombinantly produced LTB/CTB hybrid protein.

PubMed

Lundgren, A; Leach, S; Tobias, J; Carlin, N; Gustafsson, B; Jertborn, M; Bourgeois, L; Walker, R; Holmgren, J; Svennerholm, A-M

2013-02-06

We have developed a new oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea containing killed recombinant E. coli bacteria expressing increased levels of ETEC colonization factors (CFs) and a recombinant protein (LCTBA), i.e. a hybrid between the binding subunits of E. coli heat labile toxin (LTB) and cholera toxin (CTB). We describe a randomized, comparator controlled, double-blind phase I trial in 60 adult Swedish volunteers of a prototype of this vaccine. The safety and immunogenicity of the prototype vaccine, containing LCTBA and an E. coli strain overexpressing the colonization factor CFA/I, was compared to a previously developed oral ETEC vaccine, consisting of CTB and inactivated wild type ETEC bacteria expressing CFA/I (reference vaccine). Groups of volunteers were given two oral doses of either the prototype or the reference vaccine; the prototype vaccine was administered at the same or a fourfold higher dosage than the reference vaccine. The prototype vaccine was found to be safe and equally well-tolerated as the reference vaccine at either dosage tested. The prototype vaccine induced mucosal IgA (fecal secretory IgA and intestine-derived IgA antibody secreting cell) responses to both LTB and CFA/I, as well as serum IgA and IgG antibody responses to LTB. Immunization with LCTBA resulted in about twofold higher mucosal and systemic IgA responses against LTB than a comparable dose of CTB. The higher dose of the prototype vaccine induced significantly higher fecal and systemic IgA responses to LTB and fecal IgA responses to CFA/I than the reference vaccine. These results demonstrate that CF over-expression and inclusion of the LCTBA hybrid protein in an oral inactivated ETEC vaccine does not change the safety profile when compared to a previous generation of such a vaccine and that the prototype vaccine induces significant dose dependent mucosal immune responses against CFA/I and LTB. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile toxin (LT), heat-stable toxins (STa, STb), and Shiga toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC).

PubMed

Rausch, Dana; Ruan, Xiaosai; Nandre, Rahul; Duan, Qiangde; Hashish, Emad; Casey, Thomas A; Zhang, Weiping

2017-04-01

Enterotoxigenic Escherichia coli (ETEC) strains are the main cause of diarrhea in pigs. Pig diarrhea especially post-weaning diarrhea remains one of the most important swine diseases. ETEC bacterial fimbriae including K88, F18, 987P, K99 and F41 promote bacterial attachment to intestinal epithelial cells and facilitate ETEC colonization in pig small intestine. ETEC enterotoxins including heat-labile toxin (LT) and heat-stable toxins type Ia (porcine-type STa) and type II (STb) stimulate fluid hyper-secretion, leading to watery diarrhea. Blocking bacteria colonization and/or neutralizing enterotoxicity of ETEC toxins are considered effective prevention against ETEC diarrhea. In this study, we applied the MEFA (multiepitope fusion antigen) strategy to create toxoid MEFAs that carried antigenic elements of ETEC toxins, and examined for broad antitoxin immunogenicity in a murine model. By embedding STa toxoid STa P12F (NTFYCCELCCNFACAGCY), a STb epitope (KKDLCEHY), and an epitope of Stx2e A subunit (QSYVSSLN) into the A1 peptide of a monomeric LT toxoid (LT R192G ), two toxoid MEFAs, 'LT R192G -STb-Stx2e-STa P12F ' and 'LT R192G -STb-Stx2e-3xSTa P12F ' which carried three copies of STa P12F , were constructed. Mice intraperitoneally immunized with each toxoid MEFA developed IgG antibodies to all four toxins. Induced antibodies showed in vitro neutralizing activities against LT, STa, STb and Stx2e toxins. Moreover, suckling piglets born by a gilt immunized with 'LT R192G -STb-Stx2e-3xSTa P12F ' were protected when challenged with ETEC strains, whereas piglets born by a control gilt developed diarrhea. Results from this study showed that the toxoid MEFA induced broadly antitoxin antibodies, and suggested potential application of the toxoid MEFA for developing a broad-spectrum vaccine against ETEC diarrhea in pigs. Copyright © 2016 Elsevier B.V. All rights reserved.

A Chimeric protein of CFA/I, CS6 subunits and LTB/STa toxoid protects immunized mice against enterotoxigenic Escherichia coli.

PubMed

Zeinalzadeh, Narges; Salmanian, Ali Hatef; Goujani, Goli; Amani, Jafar; Ahangari, Ghasem; Akhavian, Asal; Jafari, Mahyat

2017-07-01

Enterotoxigenic Escherichia Coli (ETEC) strains are the commonest bacteria causing diarrhea in children in developing countries and travelers to these areas. Colonization factors (CFs) and enterotoxins are the main virulence determinants in ETEC pathogenesis. Heterogeneity of CFs is commonly considered the bottleneck to developing an effective vaccine. It is believed that broad spectrum protection against ETEC would be achieved by induced anti-CF and anti-enterotoxin immunity simultaneously. Here, a fusion antigen strategy was used to construct a quadrivalent recombinant protein called 3CL and composed of CfaB, a structural subunit of CFA/I, and CS6 structural subunits, LTB and STa toxoid of ETEC. Its anti-CF and antitoxin immunogenicity was then assessed. To achieve high-level expression, the 3CL gene was synthesized using E. coli codon bias. Female BALB/C mice were immunized with purified recombinant 3CL. Immunized mice developed antibodies that were capable of detecting each recombinant subunit in addition to native CS6 protein and also protected the mice against ETEC challenge. Moreover, sera from immunized mice also neutralized STa toxin in a suckling mouse assay. These results indicate that 3CL can induce anti-CF and neutralizing antitoxin antibodies along with introducing CFA/I as a platform for epitope insertion. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Antibodies derived from an enterotoxigenic Escherichia coli (ETEC) adhesin tip MEFA (multiepitope fusion antigen) against adherence of nine ETEC adhesins: CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA.

PubMed

Nandre, Rahul M; Ruan, Xiaosai; Duan, Qiangde; Sack, David A; Zhang, Weiping

2016-06-30

Diarrhea continues to be a leading cause of death in children younger than 5 years in developing countries. Enterotoxigenic Escherichia coli (ETEC) is a leading bacterial cause of children's diarrhea and travelers' diarrhea. ETEC bacteria initiate diarrheal disease by attaching to host receptors at epithelial cells and colonizing in small intestine. Therefore, preventing ETEC attachment has been considered the first line of defense against ETEC diarrhea. However, developing vaccines effectively against ETEC bacterial attachment encounters challenge because ETEC strains produce over 23 immunologically heterogeneous adhesins. In this study, we applied MEFA (multiepitope fusion antigen) approach to integrate epitopes from adhesin tips or adhesive subunits of CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS21 and EtpA adhesins and to construct an adhesin tip MEFA peptide. We then examined immunogenicity of this tip MEFA in mouse immunization, and assessed potential application of this tip MEFA for ETEC vaccine development. Data showed that mice intraperitoneally immunized with this adhesin tip MEFA developed IgG antibody responses to all nine ETEC adhesins. Moreover, ETEC and E. coli bacteria expressing these nine adhesins, after incubation with serum of the immunized mice, exhibited significant reduction in attachment to Caco-2 cells. These results indicated that anti-adhesin antibodies induced by this adhesin tip MEFA blocked adherence of the most important ETEC adhesins, suggesting this multivalent tip MEFA may be useful for developing a broadly protective anti-adhesin vaccine against ETEC diarrhea. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal Vaccination with a Fimbrial Tip Adhesin and Passive Protection of Neonatal Mice against Lethal Human Enterotoxigenic Escherichia coli Challenge

PubMed Central

Luiz, Wilson B.; Rodrigues, Juliana F.; Crabb, Joseph H.

2015-01-01

Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 × 107 bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20× LD50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation. PMID:26371126

Injury and mechanism of recombinant E. coli expressing STa on piglets colon.

PubMed

Lv, Yang; Li, Xueni; Zhang, Lin; Shi, Yutao; DU, Linxiao; Ding, Binying; Hou, Yongqing; Gong, Joshua; Wu, Tao

2018-02-09

Enterotoxigenic Escherichia coli (ETEC) is primary pathogenic bacteria of piglet diarrhea, over two thirds of piglets diarrhea caused by ETEC are resulted from STa-producing ETEC strains. This experiment was conducted to construct the recombinant E. coli expressing STa and study the injury and mechanism of recombinant E. coli expressing STa on 7 days old piglets colon. Twenty-four 7 days old piglets were allotted to four treatments: control group, STa group (2 × 10 9 CFU E. coli LMG194-STa), LMG194 group (2 × 10 9 CFU E. coli LMG194) and K88 group (2 × 10 9 CFU E. coli K88). The result showed that E. coli infection significantly increased diarrhea rates; changed DAO activity in plasma and colon; damaged colonic mucosal morphology including crypt depth, number of globet cells, density of lymphocytes and lamina propria cell density; substantially reduced antioxidant capacity by altering activities of GSH-Px, SOD, and TNOS and productions of MDA and H 2 O 2 ; obviously decreased AQP3, AQP4 and KCNJ13 protein expression levels; substantially altered the gene expression levels of inflammatory cytokines. Conclusively, STa group had the biggest effect on these indices in four treatment groups. These results suggested that the recombinant strain expressed STa can induce piglets diarrhea and colonic morphological and funtional damage by altering expression of proteins connect to transportation function and genes associated with intestinal injury and inflammatory cytokines.

Injury and mechanism of recombinant E. coli expressing STa on piglets colon

PubMed Central

LV, Yang; LI, Xueni; ZHANG, Lin; SHI, Yutao; DU, Linxiao; DING, Binying; HOU, Yongqing; GONG, Joshua; WU, Tao

2017-01-01

Enterotoxigenic Escherichia coli (ETEC) is primary pathogenic bacteria of piglet diarrhea, over two thirds of piglets diarrhea caused by ETEC are resulted from STa-producing ETEC strains. This experiment was conducted to construct the recombinant E. coli expressing STa and study the injury and mechanism of recombinant E. coli expressing STa on 7 days old piglets colon. Twenty-four 7 days old piglets were allotted to four treatments: control group, STa group (2 × 109 CFU E. coli LMG194-STa), LMG194 group (2 × 109 CFU E. coli LMG194) and K88 group (2 × 109 CFU E. coli K88). The result showed that E. coli infection significantly increased diarrhea rates; changed DAO activity in plasma and colon; damaged colonic mucosal morphology including crypt depth, number of globet cells, density of lymphocytes and lamina propria cell density; substantially reduced antioxidant capacity by altering activities of GSH-Px, SOD, and TNOS and productions of MDA and H2O2; obviously decreased AQP3, AQP4 and KCNJ13 protein expression levels; substantially altered the gene expression levels of inflammatory cytokines. Conclusively, STa group had the biggest effect on these indices in four treatment groups. These results suggested that the recombinant strain expressed STa can induce piglets diarrhea and colonic morphological and funtional damage by altering expression of proteins connect to transportation function and genes associated with intestinal injury and inflammatory cytokines. PMID:29187713

Structure and function of Enterotoxigenic Escherichia coli fimbriae from differing assembly pathways

PubMed Central

Mortezaei, Narges; Epler, Chelsea R.; Shao, Paul P.; Shirdel, Mariam; Singh, Bhupender; McVeigh, Annette; Uhlin, Bernt Eric; Savarino, Stephen J.; Andersson, Magnus; Bullitt, Esther

2014-01-01

Pathogenic enterotoxigenic Escherichia coli (ETEC) are the major bacterial cause of diarrhea in young children in developing countries and in travelers, causing significant mortality in children. Adhesive fimbriae are a prime virulence factor for ETEC, initiating colonization of the small intestinal epithelium. Similar to other Gram-negative bacteria, ETEC express one or more diverse fimbriae, some assembled by the chaperone-usher pathway and others by the alternate chaperone pathway. Here we elucidate structural and biophysical aspects and adaptations of each fimbrial type to its respective host niche. CS20 fimbriae are compared to CFA/I fimbriae, which are two ETEC fimbriae assembled via different pathways, and to P-fimbriae from uropathogenic E. coli. Many fimbriae unwind from their native helical filament to an extended linear conformation under force, thereby sustaining adhesion by reducing load at the point of contact between the bacterium and the target cell. CFA/I fimbriae require the least force to unwind, followed by CS20 fimbriae and then P-fimbriae, which require the highest unwinding force. We conclude from our electron microscopy reconstructions, modeling, and force spectroscopy data that the target niche plays a central role in the biophysical properties of fimbriae that are critical for bacterial pathophysiology. PMID:25355550

Administration of probiotics influences F4 (K88)-positive enterotoxigenic Escherichia coli attachment and intestinal cytokine expression in weaned pigs.

PubMed

Daudelin, Jean-François; Lessard, Martin; Beaudoin, Frédéric; Nadeau, Eric; Bissonnette, Nathalie; Boutin, Yvan; Brousseau, Jean-Philippe; Lauzon, Karoline; Fairbrother, John Morris

2011-05-23

This study evaluated the effect of the probiotics Pediococcus acidilactici and Saccharomyces cerevisiae boulardii on the intestinal colonization of O149 enterotoxigenic Escherichia coli harbouring the F4 (K88) fimbriae (ETEC F4) and on the expression of ileal cytokines in weaned pigs. At birth, different litters of pigs were randomly assigned to one of the following treatments: 1) control without antibiotics or probiotics (CTRL); 2) reference group in which chlortetracycline and tiamulin were added to weanling feed (ATB); 3) P. acidilactici; 4) S. cerevisiae boulardii; or 5) P. acidilactici + S. cerevisiae boulardii. Probiotics were administered daily (1 × 10(9) CFU per pig) during the lactation period and after weaning (day 21). At 28 days of age, all pigs were orally challenged with an ETEC F4 strain, and a necropsy was performed 24 h later. Intestinal segments were collected to evaluate bacterial colonization in the small intestine and ileal cytokine expressions. Attachment of ETEC F4 to the intestinal mucosa was significantly reduced in pigs treated with P. acidilactici or S. cerevisiae boulardii in comparison with the ATB group (P = 0.01 and P = 0.03, respectively). In addition, proinflammatory cytokines, such as IL-6, were upregulated in ETEC F4 challenged pigs treated with P. acidilactici alone or in combination with S. cerevisiae boulardii compared with the CTRL group. In conclusion, the administration of P. acidilactici or S. cerevisiae boulardii was effective in reducing ETEC F4 attachment to the ileal mucosa, whereas the presence of P. acidilactici was required to modulate the expression of intestinal inflammatory cytokines in pigs challenged with ETEC F4.

Construction and phase I clinical evaluation of the safety and immunogenicity of a candidate enterotoxigenic Escherichia coli vaccine strain expressing colonization factor antigen CFA/I.

PubMed

Turner, Arthur K; Beavis, Juliet C; Stephens, Jonathan C; Greenwood, Judith; Gewert, Cornelia; Thomas, Nicola; Deary, Alison; Casula, Gabriella; Daley, Alexandra; Kelly, Paul; Randall, Roger; Darsley, Michael J

2006-02-01

Oral delivery of toxin-negative derivatives of enterotoxigenic Escherichia coli (ETEC) that express colonization factor antigens (CFA) with deletions of the aroC, ompC, ompF, and toxin genes may be an effective approach to vaccination against ETEC-associated diarrhea. We describe the creation and characterization of an attenuated CFA/I-expressing ETEC vaccine candidate, ACAM2010, from a virulent isolate in which the heat-stable enterotoxin (ST) and CFA/I genes were closely linked and on the same virulence plasmid as the enteroaggregative E. coli heat-stable toxin (EAST1) gene. A new suicide vector (pJCB12) was constructed and used to delete the ST and EAST1 genes and to introduce defined deletion mutations into the aroC, ompC, and ompF chromosomal genes. A phase I trial, consisting of an open-label dose escalation phase in 18 adult outpatient volunteers followed by a placebo-controlled double-blind phase in an additional 31 volunteers, was conducted. The vaccine was administered in two formulations, fresh culture and frozen suspension. These were both well tolerated, with no evidence of significant adverse events related to vaccination. Immunoglobulin A (IgA) and IgG antibody-secreting cells specific for CFA/I were assayed by ELISPOT. Positive responses (greater than twofold increase) were seen in 27 of 37 (73%) subjects who received the highest dose level of vaccine (nominally 5 x 10(9) CFU). Twenty-nine of these volunteers were secreting culturable vaccine organisms at day 3 following vaccination; five were still positive on day 7, with a single isolation on day 13. This live attenuated bacterial vaccine is safe and immunogenic in healthy adult volunteers.

Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated With Early Childhood Diarrhea in Rural Egypt

DTIC Science & Technology

2004-12-01

2004, American Society for Microbiology. All Rights Reserved. Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated with Early Childhood...Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We...expressed both toxins. The most common CF phenotypes were colonization factor antigen I (CFA/I) (10%), coli surface antigen 6 (CS6) (9%), CS14 (6%), and

Pathogenicity and Phenotypic Characterization of Enterotoxigenic Escherichia coli Isolates from a Birth Cohort of Children in Rural Egypt

PubMed Central

Shaheen, Hind I.; Amine, Mohamed; Hassan, Khaled; Sanders, John W.; Riddle, Mark S.; Armstrong, Adam W.; Svennerholm, Ann-Mari; Sebeny, Peter J.; Klena, John D.; Young, Sylvia Y. N.; Frenck, Robert W.

2014-01-01

Enterotoxigenic Escherichia coli (ETEC) has consistently been the predominant bacterial cause of diarrhea in many birth cohort- and hospital-based studies conducted in Egypt. We evaluated the pathogenicity of ETEC isolates in a birth cohort of children living in a rural community in Egypt. Between 2004 and 2007, we enrolled and followed 348 children starting at birth until their second year of life. A stool sample and two rectal swabs were collected from children during twice-weekly visits when they presented with diarrhea and were collected every 2 weeks if no diarrhea was reported. From routine stool cultures, five E. coli-like colonies were screened for ETEC enterotoxins using a GM1 enzyme-linked immunosorbent assay (ELISA). The isolates were screened against a panel of 12 colonization factor antigens (CFAs) by a dot blot assay. A nested case-control study evaluated the association between initial or repeat excretion of ETEC and the occurrences of diarrhea. The pathogenicity of ETEC was estimated in symptomatic children compared to that in asymptomatic controls. ETEC was significantly associated with diarrhea (crude odds ratio, 1.37; 95% confidence interval [CI], 1.24 to 1.52). The distribution of ETEC enterotoxins varied between the symptomatic children (44.2% heat-labile toxin [LT], 38.5% heat-stable toxin [ST], and 17.3% LT/ST) and asymptomatic children (55.5% LT, 34.6% ST, and 9.9% LT/ST) (P < 0.001). The CFAs CFA/I (n = 61), CS3 (n = 8), CS1 plus CS3 (n = 24), CS2 plus CS3 (n = 18), CS6 (n = 45), CS5 plus CS6 (n = 11), CS7 (n = 25), and CS14 (n = 32) were frequently detected in symptomatic children, while CS6 (n = 66), CS12 (n = 51), CFA/I (n = 43), and CS14 (n = 20) were detected at higher frequencies among asymptomatic children. While all toxin phenotypes were associated with diarrheal disease after the initial exposure, only ST and LT/ST-expressing ETEC isolates (P < 0.0001) were associated with disease in repeat infections. The role of enterotoxins and pathogenicity during repeat ETEC infections appears to be variable and dependent on the coexpression of specific CFAs. PMID:24478492

Maternal vaccination with a fimbrial tip adhesin and passive protection of neonatal mice against lethal human enterotoxigenic Escherichia coli challenge.

PubMed

Luiz, Wilson B; Rodrigues, Juliana F; Crabb, Joseph H; Savarino, Stephen J; Ferreira, Luis C S

2015-12-01

Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 × 10(7) bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20× LD50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effect of added dietary threonine on growth performance, health, immunity and gastrointestinal function of weaning pigs with differing genetic susceptibility to Escherichia coli infection and challenged with E. coli K88ac.

PubMed

Trevisi, P; Corrent, E; Mazzoni, M; Messori, S; Priori, D; Gherpelli, Y; Simongiovanni, A; Bosi, P

2015-06-01

Threonine (Thr) is important for mucin and immunoglobulin production. We studied the effect of added dietary Thr on growth performance, health, immunity and gastrointestinal function of weaning pigs with differing genetic susceptibility to E. coli K88ac (ETEC) infection and challenged with ETEC. Forty-eight 24-day-old weaned pigs were divided into two groups by their ETEC susceptibility using mucin 4 (MUC4) gene as a marker (2 MUC4(-/-) , not-susceptible, and 2 MUC4(+/+) , susceptible, pigs per litter). Within genotype, pigs were fed two different diets: 8.5 (LThr) or 9.0 (HThr) g Thr/kg. Pigs were orally challenged on day 7 after weaning and slaughtered on day 12 or 13 after weaning. Before ETEC challenge, HThr pigs ate more (p < 0.05). The diet did not affect post-challenge growth, but HThr tended to increase post-challenge feed efficiency (p = 0.087) and overall growth (p = 0.087) and feed efficiency (p = 0.055). Before challenge, HThr pigs excreted less E. coli (p < 0.05), while after challenge, diet did not affect the number of days with diarrhoea and ETEC excretion. MUC4(+/+) pigs responded to the challenge with more diarrhoea, ETEC excretion and anti-K88 IgA in blood and jejunal secretion (p < 0.001). HThr pigs had a higher increase of anti-K88 IgA values in jejunal secretion (p = 0.089) and in blood (p = 0.089, in MUC4(+/+) pigs only). Thr did not affect total IgA and IgM values, morphometry of jejunum, goblet cells count in colon, total mucin from jejunum and colon, but varied jejunal goblet cells counts (p < 0.05). In the first two post-weaning weeks, 8.5 g Thr/kg diet may be not sufficient to optimize initial feed intake, overall feed efficiency and intestinal IgA secretion and to control the gut microbiota in the first post-weaning week, irrespective of the pig genetic susceptibility to ETEC infection. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Cloning and expression of colonization factor antigen I (CFA/I) epitopes of enterotoxigenic Escherichia coli (ETEC) in Salmonella flagellin.

PubMed

Luna, M G; Martins, M M; Newton, S M; Costa, S O; Almeida, D F; Ferreira, L C

1997-01-01

Oligonucleotides coding for linear epitopes of the fimbrial colonization factor antigen I (CFA/I) of enterotoxigenic Escherichia coli (ETEC) were cloned and expressed in a deleted form of the Salmonella muenchen flagellin fliC (H1-d) gene. Four synthetic oligonucleotide pairs coding for regions corresponding to amino acids 1 to 15 (region I), amino acids 11 to 25 (region II), amino acids 32 to 45 (region III) and amino acids 88 to 102 (region IV) were synthesized and cloned in the Salmonella flagellin-coding gene. All four hybrid flagellins were exported to the bacterial surface where they produced flagella, but only three constructs were fully motile. Sera recovered from mice immunized with intraperitoneal injections of purified flagella containing region II (FlaII) or region IV (FlaIV) showed high titres against dissociated solid-phase-bound CFA/I subunits. Hybrid flagellins containing region I (FlaI) or region III (FlaIII) elicited a weak immune response as measured in enzyme-linked immunosorbent assay (ELISA) with dissociated CFA/I subunits. None of the sera prepared with purified hybrid flagella were able to agglutinate or inhibit haemagglutination promoted by CFA/I-positive strains. Moreover, inhibition ELISA tests indicated that antisera directed against region I, II, III or IV cloned in flagellin were not able to recognize surface-exposed regions on the intact CFA/I fimbriae.

A structural basis for sustained bacterial adhesion: biomechanical properties of CFA/I pili.

PubMed

Andersson, Magnus; Björnham, Oscar; Svantesson, Mats; Badahdah, Arwa; Uhlin, Bernt Eric; Bullitt, Esther

2012-02-03

Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrheal disease worldwide. Adhesion pili (or fimbriae), such as the CFA/I (colonization factor antigen I) organelles that enable ETEC to attach efficiently to the host intestinal tract epithelium, are critical virulence factors for initiation of infection. We characterized the intrinsic biomechanical properties and kinetics of individual CFA/I pili at the single-organelle level, demonstrating that weak external forces (7.5 pN) are sufficient to unwind the intact helical filament of this prototypical ETEC pilus and that it quickly regains its original structure when the force is removed. While the general relationship between exertion of force and an increase in the filament length for CFA/I pili associated with diarrheal disease is analogous to that of P pili and type 1 pili, associated with urinary tract and other infections, the biomechanical properties of these different pili differ in key quantitative details. Unique features of CFA/I pili, including the significantly lower force required for unwinding, the higher extension speed at which the pili enter a dynamic range of unwinding, and the appearance of sudden force drops during unwinding, can be attributed to morphological features of CFA/I pili including weak layer-to-layer interactions between subunits on adjacent turns of the helix and the approximately horizontal orientation of pilin subunits with respect to the filament axis. Our results indicate that ETEC CFA/I pili are flexible organelles optimized to withstand harsh motion without breaking, resulting in continued attachment to the intestinal epithelium by the pathogenic bacteria that express these pili. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity

PubMed Central

Ruan, Xiaosai; Sack, David A.; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development. PMID:25803825

Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity.

PubMed

Ruan, Xiaosai; Sack, David A; Zhang, Weiping

2015-01-01

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development.

Effect of maternal supplementation with seaweed extracts on growth performance and aspects of gastrointestinal health of newly weaned piglets after challenge with enterotoxigenic Escherichia coli K88.

PubMed

Heim, G; Sweeney, T; O'Shea, C J; Doyle, D N; O'Doherty, J V

2014-12-28

In the present study, a 2 × 2 factorial arrangement was conducted to investigate the effect of maternal supplementation with seaweed extracts ( - SWE v. +SWE, n 20) from day 83 of gestation until weaning (day 28) on post-weaning (PW) growth performance, faecal score, faecal enterotoxigenic Escherichia coli (ETEC) toxin quantification, intestinal histology and cytokine mRNA of unchallenged and ETEC-challenged pigs. Pigs were ETEC challenged on day 9 PW. There was a maternal treatment × challenge (SWE × ETEC) interaction effect on growth performance and faecal score (P< 0.05). Pigs from SWE-supplemented sows and ETEC-challenged (SE) had higher average daily gain (ADG) during 0-13 d PW and reduced faecal score during 0-72 h post-challenge than those from basal-fed sows and ETEC-challenged (BE) (P< 0.05). However, there was no difference between unchallenged pigs from the SWE-supplemented sows (SC) and basal-fed sows (BC) (P>0.10). Pigs from the SWE-supplemented sows had reduced heat-labile enterotoxin gene copy numbers than those from the basal-fed sows (P< 0.05). Maternal SWE supplementation increased the villus height in the ileum of pigs (P< 0.05). There was a SWE × ETEC interaction effect (P< 0.05) on IL-6 mRNA and a SWE × gastrointestinal (GI) region interaction effect (P< 0.05) on transforming growth factor-β1 (TGF-β1) and TNF-α mRNA. IL-6 mRNA was down-regulated in SC pigs than BC pigs (P< 0.05). However, there was no difference in IL-6 mRNA between SE and BE pigs. The mRNA of TGF-β1 and TNF-α was down-regulated in the colon of pigs from the SWE-supplemented sows compared with those from the basal-fed sows (P< 0.05). However, there was no difference in TGF-β1 and TNF-α mRNA in the ileum between the pigs from the SWE-supplemented sows and basal-fed sows. In conclusion, maternal SWE supplementation improves ADG and the aspects of GI health of weaned pigs following an ETEC challenge.

Enterotoxigenic Escherichia coli strains are highly prevalent in Ugandan piggeries but disease outbreaks are masked by antibiotic prophylaxis.

PubMed

Okello, Emmanuel; Moonens, Kristof; Erume, Joseph; De Greve, Henri

2015-01-01

Post-weaning diarrhea (PWD) caused by enterotoxigenic Escherichia coli (ETEC) is an important disease of newly weaned piglets. ETEC strains commonly express F4 and/or F18 fimbriae that attach to carbohydrate receptors present on the intestinal epithelium during colonization. The disease status in the Ugandan piggeries had previously not been studied. In this cross-sectional sero-survey and clinical outbreak monitoring, we found very high sero-prevalence levels of both anti-F4 (70.5%) and anti-F18 (73.7%) antibodies, despite limited cases of clinical outbreaks. Strains isolated from these cases were typically F18(+) ETEC. High antibiotic resistance and multi-drug resistance were characteristics of the isolates, with highest resistance level of over 95% to commonly used antibiotics such as penicillin and tetracycline. We conclude that ETEC infections are widely spread on farms in Central Uganda but clinical disease outbreaks were masked by the management practices on these farms, like the use of extensive antibiotic prophylaxis.

Identification of Escherichia coli F4ac-binding proteins in porcine milk fat globule membrane

PubMed Central

Novakovic, Predrag; Huang, Yanyun Y.; Lockerbie, Betty; Shahriar, Farshid; Kelly, John; Gordon, John R.; Middleton, Dorothy M.; Loewen, Matthew E.; Kidney, Beverly A.; Simko, Elemir

2015-01-01

F4ac-positive enterotoxigenic Escherichia coli (ETEC) must attach to the intestinal mucosa to cause diarrhea in piglets. Prevention of bacterial attachment to the intestinal mucosa is the most effective defense against ETEC-induced diarrhea. Porcine milk fat globule membranes (MFGM) were shown to be able to inhibit attachment of ETEC to the intestinal brush border; however, the specific components of porcine MFGM that inhibited attachment of ETEC to enterocytes were not identified. Accordingly, the purpose of this study was to identify F4ac-binding MFGM proteins by overlay Western blot and affinity chromatography. The proteome of porcine MFGM was characterized and the following F4ac-binding proteins were detected by overlay Western blot and affinity chromatography: lactadherin, butyrophilin, adipophilin, acyl-CoA synthetase 3, and fatty acid-binding protein 3. The biological function of these proteins was not investigated but it is possible that their interaction with F4ac fimbria interferes with bacterial attachment and colonization. PMID:25852227

Single Chain Variable Fragments Produced in Escherichia coli against Heat-Labile and Heat-Stable Toxins from Enterotoxigenic E. coli.

PubMed

Ozaki, Christiane Y; Silveira, Caio R F; Andrade, Fernanda B; Nepomuceno, Roberto; Silva, Anderson; Munhoz, Danielle D; Yamamoto, Bruno B; Luz, Daniela; Abreu, Patrícia A E; Horton, Denise S P Q; Elias, Waldir P; Ramos, Oscar H P; Piazza, Roxane M F

2015-01-01

Diarrhea is a prevalent pathological condition frequently associated to the colonization of the small intestine by enterotoxigenic Escherichia coli (ETEC) strains, known to be endemic in developing countries. These strains can produce two enterotoxins associated with the manifestation of clinical symptoms that can be used to detect these pathogens. Although several detection tests have been developed, minimally equipped laboratories are still in need of simple and cost-effective methods. With the aim to contribute to the development of such diagnostic approaches, we describe here two mouse hybridoma-derived single chain fragment variable (scFv) that were produced in E. coli against enterotoxins of ETEC strains. Recombinant scFv were developed against ETEC heat-labile toxin (LT) and heat-stable toxin (ST), from previously isolated hybridoma clones. This work reports their design, construction, molecular and functional characterization against LT and ST toxins. Both antibody fragments were able to recognize the cell-interacting toxins by immunofluorescence, the purified toxins by ELISA and also LT-, ST- and LT/ST-producing ETEC strains. The developed recombinant scFvs against LT and ST constitute promising starting point for simple and cost-effective ETEC diagnosis.

Immunogenicity and protective efficacy of a single-dose live non-pathogenic Escherichia coli oral vaccine against F4-positive enterotoxigenic Escherichia coli challenge in pigs.

PubMed

Fairbrother, John Morris; Nadeau, Éric; Bélanger, Louise; Tremblay, Cindy-Love; Tremblay, Danielle; Brunelle, Mélanie; Wolf, Regina; Hellmann, Klaus; Hidalgo, Álvaro

2017-01-05

Enterotoxigenic Escherichia coli strains expressing F4 (K88) fimbriae (F4-ETEC) are one of the most important causes of post-weaning diarrhea (PWD) in pigs. F4, a major antigen, plays an important role in the early steps of the infection. Herein, the efficacy of a live oral vaccine consisting of a non-pathogenic E. coli strain expressing F4 for protection of pigs against PWD was evaluated. Three blinded, placebo-controlled, block design, parallel-group confirmatory experiments were conducted, using an F4-ETEC PWD challenge model, each with a different vaccination-challenge interval (3, 7, and 21days). The pigs were vaccinated via the drinking water with a single dose of the Coliprotec® F4 vaccine one day post-weaning. Efficacy was assessed by evaluating diarrhea, clinical observations, intestinal fluid accumulation, weight gain, intestinal colonization and fecal shedding of F4-ETEC. The immune response was evaluated by measuring serum and intestinal F4-specific antibodies. The administration of the vaccine resulted in a significant reduction of the incidence of moderate to severe diarrhea, ileal colonization by F4-ETEC, and fecal shedding of F4-ETEC after the heterologous challenge at 7 and 21days post-vaccination. The 7-day onset of protection was associated with an increase of serum anti-F4 IgM whereas the 21-day duration of protection was associated with an increase of both serum anti-F4 IgM and IgA. Significant correlations between levels of serum and intestinal secretory anti-F4 antibodies were detected. Maternally derived F4-specific serum antibodies did not interfere with the vaccine efficacy. The evaluation of protection following a challenge three days after vaccination showed a reduction of the severity and the duration of diarrhea and of fecal shedding of F4-ETEC. The 7-day onset and the 21-day duration of protection induced by Coliprotec® F4 vaccine administered once in drinking water to pigs of at least 18days of age were confirmed by protection against F4-ETEC and induction of F4-specific protective immunity. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Enterotoxigenic Escherichia coli Adhesin-Toxoid Multiepitope Fusion Antigen CFA/I/II/IV-3xSTaN12S-mnLTG192G/L211A-Derived Antibodies Inhibit Adherence of Seven Adhesins, Neutralize Enterotoxicity of LT and STa Toxins, and Protect Piglets against Diarrhea.

PubMed

Nandre, Rahul; Ruan, Xiaosai; Lu, Ti; Duan, Qiangde; Sack, David; Zhang, Weiping

2018-03-01

Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of children's diarrhea and travelers' diarrhea. Vaccines inducing antibodies to broadly inhibit bacterial adherence and to neutralize toxin enterotoxicity are expected to be effective against ETEC-associated diarrhea. 6×His-tagged adhesin-toxoid fusion proteins were shown to induce neutralizing antibodies to several adhesins and LT and STa toxins (X. Ruan, D. A. Sack, W. Zhang, PLoS One 10:e0121623, 2015, https://doi.org/10.1371/journal.pone.0121623). However, antibodies derived from His-tagged CFA/I/II/IV-2xSTa A14Q -dmLT or CFA/I/II/IV-2xSTa N12S -dmLT protein were less effective in neutralizing STa enterotoxicity and were not evaluated in vivo for efficacy against ETEC diarrhea. Additionally, His-tagged proteins are considered less desirable for human vaccines. In this study, we produced a tagless adhesin-toxoid MEFA (multiepitope fusion antigen) protein, enhanced anti-STa immunogenicity by including a third copy of STa toxoid STa N12S , and examined antigen immunogenicity in a murine model. Moreover, we immunized pregnant pigs with the tagless adhesin-toxoid MEFA protein and evaluated passive antibody protection against STa + or LT + ETEC infection in a pig challenge model. Results showed that tagless adhesin-toxoid MEFA CFA/I/II/IV-3xSTa N12S -mnLT R192G/L211A induced broad antiadhesin and antitoxin antibody responses in the intraperitoneally immunized mice and the intramuscularly immunized pigs. Mouse and pig serum antibodies significantly inhibited adherence of seven colonization factor antigen (CFA) adhesins (CFA/I and CS1 to CS6) and effectively neutralized both toxins. More importantly, suckling piglets born to the immunized mothers acquired antibodies and were protected against STa + ETEC and LT + ETEC diarrhea. These results indicated that tagless CFA/I/II/IV-3xSTa N12S -mnLT R192G/L211A induced broadly protective antiadhesin and antitoxin antibodies and demonstrate that this adhesin-toxoid MEFA is a potential antigen for developing broadly protective ETEC vaccines. Copyright © 2018 American Society for Microbiology.

Antigenicity and immunogenicity of fused B-subunit of heat labile toxin of Escherichia coli and colonization factor antigen I polyepitopes.

PubMed

Savar, Nastaran Sadat; Dashti, Amir; Darzi Eslam, Elham; Jahanian-Najafabadi, Ali; Jafari, Anis

2014-11-01

Linear B-cell epitopes ((93)AKEFEAAAL(101) and (66)PQLTDVLN(73)) of CfaB were genetically fused to ltb-(gly)5-cfaB(1-25). Sera of rabbits immunized with fusion proteins reacted strongly with solid-phase bound ETEC bacteria bearing CFA/I fimbriae. Sera failed to agglutinate or inhibit hemagglutination promoted by CFA/I-positive strain which may be due to solvent inaccessibility of epitope residues on intact fimbriae. Copyright © 2014 Elsevier B.V. All rights reserved.

Bile Acids Improve the Antimicrobial Effect of Rifaximin▿ †

PubMed Central

Darkoh, Charles; Lichtenberger, Lenard M.; Ajami, Nadim; Dial, Elizabeth J.; Jiang, Zhi-Dong; DuPont, Herbert L.

2010-01-01

Diarrhea is one of the most common infirmities affecting international travelers, occurring in 20 to 50% of persons from industrialized countries visiting developing regions. Enterotoxigenic Escherichia coli (ETEC) is the most common causative agent and is isolated from approximately half of the cases of traveler's diarrhea. Rifaximin, a largely water-insoluble, nonabsorbable (<0.4%) antibiotic that inhibits bacterial RNA synthesis, is approved for use for the treatment of traveler's diarrhea caused by diarrheagenic E. coli. However, the drug has minimal effect on the bacterial flora or the infecting E. coli strain in the aqueous environment of the colon. The purpose of the present study was to evaluate the antimicrobial effect and bioavailability of rifaximin in aqueous solution in the presence and absence of physiologic concentrations of bile acids. The methods used included growth measurement of ETEC (strain H10407), rifaximin solubility measurements, total bacterial protein determination, and assessment of the functional activity of rifaximin by monitoring inhibition of bacterial β-galactosidase expression. Solubility studies showed rifaximin to be 70- to 120-fold more soluble in bile acids (approximately 30% in 4 mM bile acids) than in aqueous solution. Addition of both purified bile acids and human bile to rifaximin at subinhibitory and inhibitory concentrations significantly improved the drug's anti-ETEC effect by 71% and 73%, respectively, after 4 h. This observation was confirmed by showing a decrease in the overall amount of total bacterial protein expressed during incubation of rifaximin plus bile acids. Rifaximin-treated samples containing bile acids inhibited the expression of ETEC β-galactosidase at a higher magnitude than samples that did not contain bile acids. The study provides data showing that bile acids solubilize rifaximin on a dose-response basis, increasing the drug's bioavailability and antimicrobial effect. These observations suggest that rifaximin may be more effective in the treatment of infections in the small intestine, due to the higher concentration of bile in this region of the gastrointestinal tract than in the colon. The water insolubility of rifaximin is the likely explanation for the drug's minimal effects on colonic flora and fecal pathogens, despite in vitro susceptibility. PMID:20547807

Expression of Mucin-Type Glycoprotein K88 Receptors Strongly Correlates with Piglet Susceptibility to K88+ Enterotoxigenic Escherichia coli, but Adhesion of This Bacterium to Brush Borders Does Not

PubMed Central

Francis, David H.; Grange, Philippe A.; Zeman, David H.; Baker, Diane R.; Sun, Ronggai; Erickson, Alan K.

1998-01-01

Three antigenic variants of the K88 fimbrial adhesin exist in nature, K88ab, K88ac, and K88ad. Enterotoxigenic Escherichia coli (ETEC) strains that produce these fimbriae cause life-threatening diarrhea in some but not all young pigs. The susceptibility of pigs to these organisms has been correlated with the adherence of bacteria to isolated enterocyte brush borders. Whether that correlation holds for multiple K88 variants and over a broad genetic base of pigs is unknown and was the impetus for this study. We also desired to examine the correlation of the expression of a porcine intestinal brush border mucin-type glycoprotein (IMTGP) which binds K88ab and K88ac with the susceptibility of piglets to K88+ ETEC. Of 31 neonatal gnotobiotic pigs inoculated with K88ab+ or K88ac+ ETEC, 13 developed severe diarrhea, became dehydrated, and died or became moribund. Another pig became severely lethargic but not dehydrated. In vitro brush border adherence analysis was not possible for 10 of the severely ill pigs due to colonization by challenge strains. However, of the 17 pigs that did not become severely ill, 8 (47%) had brush borders that supported the adherence of K88ab+ and K88ac+ bacteria in vitro, suggesting a poor correlation between in vitro brush border adherence and piglet susceptibility to K88+ ETEC. By contrast, the expression of IMTGP was highly correlated with susceptibility to K88+ ETEC. Of the 12 pigs that produced IMTGP, 11 developed severe diarrhea. The other pig that produced IMTGP became lethargic but not severely diarrheic. Only 2 of 18 pigs that did not produce IMTGP became severely diarrheic. Colonizing bacteria were observed in histologic sections of intestines from all pigs that expressed IMTGP except for the one that did not develop severe diarrhea. However, colonizing bacteria were observed in histologic sections from only one pig that did not produce IMTGP. The bacterial concentration in the jejuna and ilea of pigs expressing IMTGP was significantly greater (P < 0.005) than that in pigs not expressing IMTGP. These observations suggest the IMTGP is a biologically relevant receptor for K88ab+ and K88ac+ E. coli or a correlate for expression for such a receptor. PMID:9712746

Mutations in the Histone-like Nucleoid Structuring Regulatory Gene (hns) Decrease the Adherence of Shiga Toxin-producing Escherichia coli 091:H21 Strain B2F1 to Human Colonic Epithelial Cells and Increase the Production of Hemolysin

DTIC Science & Technology

1999-10-19

osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR. J. Bacteriol. 170:2575-2583. Mobley, H. L., D. M. Green...produced by ETEC organisms is homologous to the toxin encoded by Y: cholerae . These toxins are the primary cause of the watery diarrhea associated with ETEC...Escherichia coli as a cause ofdiarrhea among children in Mexico . J. Clin. Microbiol. 25:1913-1919. Maurelli, A. T., and P. J. Sansonetti. 1988

Rice evapotranspiration at the field and canopy scales under water-saving irrigation

NASA Astrophysics Data System (ADS)

Liu, Xiaoyin; Xu, Junzeng; Yang, Shihong; Zhang, Jiangang

2018-04-01

Evapotranspiration (ET) is an important process of land surface water and thermal cycling, with large temporal and spatial variability. To reveal the effect of water-saving irrigation (WSI) on rice ET at different spatial scales and understand the cross spatial scale difference, rice ET under WSI condition at canopy (ETCML) and field scale (ETEC) were measured simultaneously by mini-lysimeter and eddy covariance (EC) in the rice season of 2014. To overcome the shortage of energy balance deficit by EC system, and evaluate the influence of energy balance closure degree on ETEC, ETEC was corrected as {ET}_{EC}^{*} by energy balance closure correction according to the evaporative fraction. Seasonal average daily ETEC, {ET}_{EC}^{*} and ETCML of rice under WSI practice were estimated as 3.12, 4.03 and 4.35 mm day-1, smaller than the values reported in flooded paddy fields. Daily ETEC, {ET}_{EC}^{*} and ETCML varied in a similar trends and reached the maximum in late tillering, then decreased along with the crop growth in late season. The value of ETEC was much lower than ETCML, and was frequently 1-2 h lagged behind ETCML. It indicated that the energy balance deficit resulted in underestimation of crop ET by EC system. The corrected value of {ET}_{EC}^{*} matched ETCML much better than ETEC, with a smaller RMSE (0.086 mm h-1) and higher R 2 (0.843) and IOA (0.961). The time lapse between {ET}_{EC}^{*} and ETCML was mostly shortened to less than 0.5 h. The multiple stepwise regression analysis indicated that net radiation ( R n) is the dominant factor for rice ET, and soil moisture ( θ) is another significant factor ( p < 0.01) in WSI rice fields. The difference between ETCML and {ET}_{EC}^{*} ({ET}_{CML} - {ET}_{EC}^{*}) were significantly ( p < 0.05) correlated with R n, air temperature ( T a), and air vapor pressure deficit ( D), and its partial correlation coefficients to R n and T a were slightly greater than D. Thus, R n, T a and D are important variables for understanding the spatial scale effect of rice ET in WSI fields, and for its cross scale conversion.

Shifting Prevalence of Major Diarrheal Pathogens in Patients Seeking Hospital Care during Floods in 1998, 2004, and 2007 in Dhaka, Bangladesh

PubMed Central

Harris, Aaron M.; Chowdhury, Fahima; Begum, Yasmin Ara; Khan, Ashraful Islam; Faruque, Abu S. G.; Svennerholm, Ann-Mari; Harris, Jason B.; Ryan, Edward T.; Cravioto, Alejandro; Calderwood, Stephen B.; Qadri, Firdausi

2009-01-01

Bangladesh experienced severe flooding and diarrheal epidemics in 2007. We compared flood data from 2007 with 2004 and 1998 for diarrheal patients attending the ICDDR,B hospital in Dhaka. In 2007, Vibrio cholerae O1 (33%), rotavirus (12%), and enterotoxigenic Escherichia coli (ETEC) (12%) were most prevalent. More severe dehydration was seen in 2007 compared with 2004 and 1998 (P < 0.001). In 2007, V. cholerae O1 Inaba (52%) and Ogawa (48%) were seen, whereas in 2004 and 1998 it was primarily Inaba and the Ogawa types, respectively (P < 0.001). In 2007, 51% of ETEC produced the heat labile toxin (LT) (P < 0.001 compared with 2004), 22% expressed the heat stable (ST) (P < 0.001), and 27% were ST/LT positive (P = 0.231). The CS7 colonization factor (CF) was the most prevalent in 2007 (20% compared with 6% in 2004; P = 0.05). Our findings demonstrate alterations in clinical features and phenotypic changes of major bacterial pathogens in the recent Bangladesh flood. PMID:18981509

Risks Associated with High-Dose Lactobacillus rhamnosus in an Escherichia coli Model of Piglet Diarrhoea: Intestinal Microbiota and Immune Imbalances

PubMed Central

Yue, Yuan; Cai, Zheng-Xing; Lu, Qing-Ping; Zhang, Lu; Weng, Xiao-Gang; Zhang, Fan-Jian; Zhou, Dong; Yang, Jin-Cai; Wang, Jiu-Feng

2012-01-01

Probiotic could be a promising alternative to antibiotics for the prevention of enteric infections; however, further information on the dose effects is required. In this study, weanling piglets were orally administered low- or high-dose Lactobacillus rhamnosus ACTT 7469 (1010 CFU/d or 1012 CFU/d) for 1 week before F4 (K88)-positive Escherichia coli challenge. The compositions of faecal and gastrointestinal microbiota were recorded; gene expression in the intestines was assessed by real-time PCR; serum tumour necrosis factor-α (TNF-α) concentrations and intestinal Toll-like receptor 4 (TLR4) were detected by ELISA and immunohistochemistry, respectively. Unexpectedly, high-dose administration increased the incidence of diarrhoea before F4+ETEC challenge, despite the fact that both doses ameliorated F4+ETEC-induced diarrhoea with increased Lactobacillus and Bifidobacterium counts accompanied by reduced coliform shedding in faeces. Interestingly, L. rhamnosus administration reduced Lactobacillus and Bifidobacterium counts in the colonic contents, and the high-dose piglets also had lower Lactobacillius and Bacteroides counts in the ileal contents. An increase in the concentration of serum TNF-α induced by F4+ETEC was observed, but the increase was delayed by L. rhamnosus. In piglets exposed to F4+ETEC, jejunal TLR4 expression increased at the mRNA and protein levels, while jejunal interleukin (IL)-8 and ileal porcine β-defensins 2 (pBD2) mRNA expression increased; however, these increases were attenuated by administration of L. rhamnosus. Notably, expression of jejunal TLR2, ileal TLR9, Nod-like receptor NOD1 and TNF-α mRNA was upregulated in the low-dose piglets after F4+ETEC challenge, but not in the high-dose piglets. These findings indicate that pretreatment with a low dose of L. rhamnosus might be more effective than a high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus pretreatment may negate the preventative effects, thus decreasing the prophylactic benefits against potential enteric pathogens. Our data suggest a safe threshold for preventative use of probiotics in clinical practice. PMID:22848393

Toxicity and immunogenicity of Enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion 3xSTa(A14Q)-LT(S63K/R192G/L211A) in a murine model.

PubMed

Zhang, Chengxian; Knudsen, David E; Liu, Mei; Robertson, Donald C; Zhang, Weiping

2013-01-01

Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC) are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT) and heat-stable type Ib toxin (STa) disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STa(P13F)) fused at the N- or C-terminus, or inside the A subunit of LT(R192G) elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011). In this study, we generated a different STa toxoid (STa(A14Q)) and a triple-mutant LT toxoid (LT(S63K/R192G/L211A), tmLT), constructed a toxoid fusion (3xSTa(A14Q)-tmLT) that carried 3 copies of STa(A14Q) for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTa(A14Q)-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea.

Comparative genomics and transcriptomics of Escherichia coli isolates carrying virulence factors of both enteropathogenic and enterotoxigenic E. coli.

PubMed

Hazen, Tracy H; Michalski, Jane; Luo, Qingwei; Shetty, Amol C; Daugherty, Sean C; Fleckenstein, James M; Rasko, David A

2017-06-14

Escherichia coli that are capable of causing human disease are often classified into pathogenic variants (pathovars) based on their virulence gene content. However, disease-associated hybrid E. coli, containing unique combinations of multiple canonical virulence factors have also been described. Such was the case of the E. coli O104:H4 outbreak in 2011, which caused significant morbidity and mortality. Among the pathovars of diarrheagenic E. coli that cause significant human disease are the enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC). In the current study we use comparative genomics, transcriptomics, and functional studies to characterize isolates that contain virulence factors of both EPEC and ETEC. Based on phylogenomic analysis, these hybrid isolates are more genomically-related to EPEC, but appear to have acquired ETEC virulence genes. Global transcriptional analysis using RNA sequencing, demonstrated that the EPEC and ETEC virulence genes of these hybrid isolates were differentially-expressed under virulence-inducing laboratory conditions, similar to reference isolates. Immunoblot assays further verified that the virulence gene products were produced and that the T3SS effector EspB of EPEC, and heat-labile toxin of ETEC were secreted. These findings document the existence and virulence potential of an E. coli pathovar hybrid that blurs the distinction between E. coli pathovars.

Structure of the CFA/III major pilin subunit CofA from human enterotoxigenic Escherichia coli determined at 0.90 Å resolution by sulfur-SAD phasing.

PubMed

Fukakusa, Shunsuke; Kawahara, Kazuki; Nakamura, Shota; Iwashita, Takaki; Baba, Seiki; Nishimura, Mitsuhiro; Kobayashi, Yuji; Honda, Takeshi; Iida, Tetsuya; Taniguchi, Tooru; Ohkubo, Tadayasu

2012-10-01

CofA, a major pilin subunit of colonization factor antigen III (CFA/III), forms pili that mediate small-intestinal colonization by enterotoxigenic Escherichia coli (ETEC). In this study, the crystal structure of an N-terminally truncated version of CofA was determined by single-wavelength anomalous diffraction (SAD) phasing using five sulfurs in the protein. Given the counterbalance between anomalous signal strength and the undesired X-ray absorption of the solvent, diffraction data were collected at 1.5 Å resolution using synchrotron radiation. These data were sufficient to elucidate the sulfur substructure at 1.38 Å resolution. The low solvent content (29%) of the crystal necessitated that density modification be performed with an additional 0.9 Å resolution data set to reduce the phase error caused by the small sulfur anomalous signal. The CofA structure showed the αβ-fold typical of type IVb pilins and showed high structural homology to that of TcpA for toxin-coregulated pili of Vibrio cholerae, including spatial distribution of key residues critical for pilin self-assembly. A pilus-filament model of CofA was built by computational docking and molecular-dynamics simulation using the previously reported filament model of TcpA as a structural template. This model revealed that the CofA filament surface was highly negatively charged and that a 23-residue-long loop between the α1 and α2 helices filled the gap between the pilin subunits. These characteristics could provide a unique binding epitope for the CFA/III pili of ETEC compared with other type IVb pili.

Lactobacillus plantarum BSGP201683 Isolated from Giant Panda Feces Attenuated Inflammation and Improved Gut Microflora in Mice Challenged with Enterotoxigenic Escherichia coli

PubMed Central

Liu, Qian; Ni, Xueqin; Wang, Qiang; Peng, Zhirong; Niu, Lili; Wang, Hengsong; Zhou, Yi; Sun, Hao; Pan, Kangcheng; Jing, Bo; Zeng, Dong

2017-01-01

In this work, we searched for an effective probiotic that can help control intestinal infection, particularly enterotoxigenic Escherichia coli K88 (ETEC) invasion, in giant panda (Ailuropoda melanoleuca). As a potential probiotic strain, Lactobacillus plantarum BSGP201683 (L. plantarum G83) was isolated from the feces of giant panda and proven beneficial in vitro. This study was aimed to evaluate the protective effect of L. plantarum G83 in mice challenged with ETEC. The mice were orally administered with 0.2 mL of PBS containing L. plantarum G83 at 0 colony-forming units (cfu) mL−1 (control; negative control, ETEC group), 5.0 × 108 cfu mL−1 (LDLP), 5.0 × 109 cfu mL−1 (MDLP), and 5.0 × 1010 cfu mL−1 (HDLP) for 14 consecutive days. At day 15, the mice (LDLP, MDLP, HDLP, and ETEC groups) were challenged with ETEC and assessed at 0, 24, and 144 h. Animal health status; chemical and biological intestinal barriers; and body weight were measured. Results showed that L. plantarum G83 supplementation protected the mouse gut mainly by attenuating inflammation and improving the gut microflora. Most indices significantly changed at 24 h after challenge compared to those at 0 and 144 h. All treatment groups showed inhibited plasma diamine oxidase activity and D-lactate concentration. Tight-junction protein expression was down-regulated, and interleukin (IL)-1β, IL-6, IL-8, TLR4, and MyD88 levels were up-regulated in the jejunum in the LDLP and MDLP groups. The number of the Enterobacteriaceae family and the heat-labile enterotoxin (LT) gene decreased (P < 0.05) in the colons in the LDLP and MDLP groups. All data indicated that L. plantarum G83 could attenuate acute intestinal inflammation caused by ETEC infection, and the low and intermediate doses were superior to the high dose. These findings suggested that L. plantarum G83 may serve as a protective probiotic for intestinal disease and merits further investigation. PMID:29018435

Lactobacillus plantarum BSGP201683 Isolated from Giant Panda Feces Attenuated Inflammation and Improved Gut Microflora in Mice Challenged with Enterotoxigenic Escherichia coli.

PubMed

Liu, Qian; Ni, Xueqin; Wang, Qiang; Peng, Zhirong; Niu, Lili; Wang, Hengsong; Zhou, Yi; Sun, Hao; Pan, Kangcheng; Jing, Bo; Zeng, Dong

2017-01-01

In this work, we searched for an effective probiotic that can help control intestinal infection, particularly enterotoxigenic Escherichia coli K88 (ETEC) invasion, in giant panda ( Ailuropoda melanoleuca ). As a potential probiotic strain, Lactobacillus plantarum BSGP201683 ( L. plantarum G83) was isolated from the feces of giant panda and proven beneficial in vitro . This study was aimed to evaluate the protective effect of L. plantarum G83 in mice challenged with ETEC. The mice were orally administered with 0.2 mL of PBS containing L. plantarum G83 at 0 colony-forming units (cfu) mL -1 (control; negative control, ETEC group), 5.0 × 10 8 cfu mL -1 (LDLP), 5.0 × 10 9 cfu mL -1 (MDLP), and 5.0 × 10 10 cfu mL -1 (HDLP) for 14 consecutive days. At day 15, the mice (LDLP, MDLP, HDLP, and ETEC groups) were challenged with ETEC and assessed at 0, 24, and 144 h. Animal health status; chemical and biological intestinal barriers; and body weight were measured. Results showed that L. plantarum G83 supplementation protected the mouse gut mainly by attenuating inflammation and improving the gut microflora. Most indices significantly changed at 24 h after challenge compared to those at 0 and 144 h. All treatment groups showed inhibited plasma diamine oxidase activity and D -lactate concentration. Tight-junction protein expression was down-regulated, and interleukin (IL)-1β, IL-6, IL-8, TLR4, and MyD88 levels were up-regulated in the jejunum in the LDLP and MDLP groups. The number of the Enterobacteriaceae family and the heat-labile enterotoxin (LT) gene decreased ( P < 0.05) in the colons in the LDLP and MDLP groups. All data indicated that L. plantarum G83 could attenuate acute intestinal inflammation caused by ETEC infection, and the low and intermediate doses were superior to the high dose. These findings suggested that L. plantarum G83 may serve as a protective probiotic for intestinal disease and merits further investigation.

Interactions of Saccharomyces cerevisiae fermentation product and in-feed antibiotic on gastrointestinal and immunological responses in piglets challenged with Escherichia coli K88+.

PubMed

Kiarie, E; Scott, M; Krause, D O; Khazanehei, H; Khafipour, E; Nyachoti, C M

2012-12-01

Interactive effects between in-feed antibiotics (PC; 0.04% chlortetracycline + 0.004% Denagard) and a Saccharomyces cerevisiae fermentation product (XPC) were investigated. Five pens of 3 pigs/pen were randomly allotted to one of six diets consisting of control (NC; no additives), XPC alone (0.2%), PC alone, or PC plus one of three levels of XPC (0.1, 0.2, or 0.4%). On day 7, all pigs were bled for baseline serum and then orally inoculated with a 6-mL dose of 2 x 10(9) cfu/mL of ciprofloxacin-resistant Escherichia coli K88(+) (ETEC). Severity of diarrhea, using fecal score (FS), was assessed on days 8, 9, and 10. On day 10, pigs were bled and 1 pig/pen was killed to obtain gastrointestinal (GIT) samples. Remaining pigs were monitored for another 4 d and then killed to obtain GIT samples. Pigs fed PC and XPC in combination of PC had a lower (P = 0.02) FS than NC. The PC pigs had lower (P = 0.02) serum interleukin-6 and XPC pigs had higher (P < 0.01) serum tumor necrosis factor-α than NC pigs. Ileal mucosal ETEC count was lower on day 10 (P = 0.04) and day 14 (P < 0.01) when additives were fed in combination. Microbiome analysis of day 10 digesta using pyrosequencing showed that pigs fed the PC with XPC had enriched (P = 0.01) Streptococcaceae family than PC fed alone. On day 10, pigs fed PC alone and in combination with XPC at a lower dose had shallower (P = 0.01) crypt depth than those fed higher doses of XPC, XPC alone, or NC. Pigs fed XPC had a thicker colon wall on day 10 (P < 0.01) compared to those fed non-XPC diets. Ileal and colonic digesta NH(3) concentration was lower (P < 0.05) for pigs fed additives-containing diets on days 10 and 14. Feeding PC or XPC reduced diarrhea and the number of ETEC attached to the ileal mucosa; however, responses suggest independent and interactive effects that might be associated with the nature of these additives.

Effects of lng Mutations on LngA Expression, Processing, and CS21 Assembly in Enterotoxigenic Escherichia coli E9034A

PubMed Central

Saldaña-Ahuactzi, Zeus; Rodea, Gerardo E.; Cruz-Córdova, Ariadnna; Rodríguez-Ramírez, Viridiana; Espinosa-Mazariego, Karina; González-Montalvo, Martín A.; Ochoa, Sara A.; González-Pedrajo, Bertha; Eslava-Campos, Carlos A.; López-Villegas, Edgar O.; Hernández-Castro, Rigoberto; Arellano-Galindo, José; Patiño-López, Genaro; Xicohtencatl-Cortes, Juan

2016-01-01

Enterotoxigenic Escherichia coli (ETEC) is a major cause of morbidity in children under 5 years of age in low- and middle-income countries and a leading cause of traveler's diarrhea worldwide. The ability of ETEC to colonize the intestinal epithelium is mediated by fimbrial adhesins, such as CS21 (Longus). This adhesin is a type IVb pilus involved in adherence to intestinal cells in vitro and bacterial self-aggregation. Fourteen open reading frames have been proposed to be involved in CS21 assembly, hitherto only the lngA and lngB genes, coding for the major (LngA) and minor (LngB) structural subunit, have been characterized. In this study, we investigated the role of the LngA, LngB, LngC, LngD, LngH, and LngP proteins in the assembly of CS21 in ETEC strain E9034A. The deletion of the lngA, lngB, lngC, lngD, lngH, or lngP genes, abolished CS21 assembly in ETEC strain E9034A and the adherence to HT-29 cells was reduced 90%, compared to wild-type strain. Subcellular localization prediction of CS21 proteins was similar to other well-known type IV pili homologs. We showed that LngP is the prepilin peptidase of LngA, and that ETEC strain E9034A has another peptidase capable of processing LngA, although with less efficiency. Additionally, we present immuno-electron microscopy images to show that the LngB protein could be localized at the tip of CS21. In conclusion, our results demonstrate that the LngA, LngB, LngC, LngD, LngH, and LngP proteins are essential for CS21 assembly, as well as for bacterial aggregation and adherence to HT-29 cells. PMID:27536289

A Selected Lactobacillus rhamnosus Strain Promotes EGFR-Independent Akt Activation in an Enterotoxigenic Escherichia coli K88-Infected IPEC-J2 Cell Model.

PubMed

Zhang, Wei; Zhu, Yao-Hong; Yang, Jin-Cai; Yang, Gui-Yan; Zhou, Dong; Wang, Jiu-Feng

2015-01-01

Enterotoxigenic Escherichia coli (ETEC) are important intestinal pathogens that cause diarrhea in humans and animals. Although probiotic bacteria may protect against ETEC-induced enteric infections, the underlying mechanisms are unknown. In this study, porcine intestinal epithelial J2 cells (IPEC-J2) were pre-incubated with and without Lactobacillus rhamnosus ATCC 7469 and then exposed to F4+ ETEC. Increases in TLR4 and NOD2 mRNA expression were observed at 3 h after F4+ ETEC challenge, but these increases were attenuated by L. rhamnosus treatment. Expression of TLR2 and NOD1 mRNA was up-regulated in cells pre-treated with L. rhamnosus. Pre-treatment with L. rhamnosus counteracted F4+ ETEC-induced increases in TNF-α concentration. Increased PGE2. concentrations were observed in cells infected with F4+ ETEC and in cells treated with L. rhamnosus only. A decrease in phosphorylated epidermal growth factor receptor (EGFR) was observed at 3 h after F4+ ETEC challenge in cells treated with L. rhamnosus. Pre-treatment with L. rhamnosus enhanced Akt phosphorylation and increased ZO-1 and occludin protein expression. Our findings suggest that L. rhamnosus protects intestinal epithelial cells from F4+ ETEC-induced damage, partly through the anti-inflammatory response involving synergism between TLR2 and NOD1. In addition, L. rhamnosus promotes EGFR-independent Akt activation, which may activate intestinal epithelial cells in response to bacterial infection, in turn increasing tight junction integrity and thus enhancing the barrier function and restricting pathogen invasion. Pre-incubation with L. rhamnosus was superior to co-incubation in reducing the adhesion of F4+ ETEC to IPEC-J2 cells and subsequently attenuating F4+ ETEC-induced mucin layer destruction and suppressing apoptosis. Our data indicate that a selected L. rhamnosus strain interacts with porcine intestinal epithelial cells to maintain the epithelial barrier and promote intestinal epithelial cell activation in response to bacterial infection, thus protecting cells from the deleterious effects of F4+ ETEC.

A Selected Lactobacillus rhamnosus Strain Promotes EGFR-Independent Akt Activation in an Enterotoxigenic Escherichia coli K88-Infected IPEC-J2 Cell Model

PubMed Central

Yang, Jin-Cai; Yang, Gui-Yan; Zhou, Dong; Wang, Jiu-Feng

2015-01-01

Enterotoxigenic Escherichia coli (ETEC) are important intestinal pathogens that cause diarrhea in humans and animals. Although probiotic bacteria may protect against ETEC-induced enteric infections, the underlying mechanisms are unknown. In this study, porcine intestinal epithelial J2 cells (IPEC-J2) were pre-incubated with and without Lactobacillus rhamnosus ATCC 7469 and then exposed to F4+ ETEC. Increases in TLR4 and NOD2 mRNA expression were observed at 3 h after F4+ ETEC challenge, but these increases were attenuated by L. rhamnosus treatment. Expression of TLR2 and NOD1 mRNA was up-regulated in cells pre-treated with L. rhamnosus. Pre-treatment with L. rhamnosus counteracted F4+ ETEC-induced increases in TNF-α concentration. Increased PGE2. concentrations were observed in cells infected with F4+ ETEC and in cells treated with L. rhamnosus only. A decrease in phosphorylated epidermal growth factor receptor (EGFR) was observed at 3 h after F4+ ETEC challenge in cells treated with L. rhamnosus. Pre-treatment with L. rhamnosus enhanced Akt phosphorylation and increased ZO-1 and occludin protein expression. Our findings suggest that L. rhamnosus protects intestinal epithelial cells from F4+ ETEC-induced damage, partly through the anti-inflammatory response involving synergism between TLR2 and NOD1. In addition, L. rhamnosus promotes EGFR-independent Akt activation, which may activate intestinal epithelial cells in response to bacterial infection, in turn increasing tight junction integrity and thus enhancing the barrier function and restricting pathogen invasion. Pre-incubation with L. rhamnosus was superior to co-incubation in reducing the adhesion of F4+ ETEC to IPEC-J2 cells and subsequently attenuating F4+ ETEC-induced mucin layer destruction and suppressing apoptosis. Our data indicate that a selected L. rhamnosus strain interacts with porcine intestinal epithelial cells to maintain the epithelial barrier and promote intestinal epithelial cell activation in response to bacterial infection, thus protecting cells from the deleterious effects of F4+ ETEC. PMID:25915861

MEFA (multiepitope fusion antigen)-Novel Technology for Structural Vaccinology, Proof from Computational and Empirical Immunogenicity Characterization of an Enterotoxigenic Escherichia coli (ETEC) Adhesin MEFA

PubMed Central

Duan, Qiangde; Lee, Kuo Hao; Nandre, Rahul M; Garcia, Carolina; Chen, Jianhan; Zhang, Weiping

2017-01-01

Vaccine development often encounters the challenge of virulence heterogeneity. Enterotoxigenic Escherichia coli (ETEC) bacteria producing immunologically heterogeneous virulence factors are a leading cause of children’s diarrhea and travelers’ diarrhea. Currently, we do not have licensed vaccines against ETEC bacteria. While conventional methods continue to make progress but encounter challenge, new computational and structure-based approaches are explored to accelerate ETEC vaccine development. In this study, we applied a structural vaccinology concept to construct a structure-based multiepitope fusion antigen (MEFA) to carry representing epitopes of the seven most important ETEC adhesins [CFA/I, CFA/II (CS1–CS3), CFA/IV (CS4–CS6)], simulated antigenic structure of the CFA/I/II/IV MEFA with computational atomistic modeling and simulation, characterized immunogenicity in mouse immunization, and examined the potential of structure-informed vaccine design for ETEC vaccine development. A tag-less recombinant MEFA protein (CFA/I/II/IV MEFA) was effectively expressed and extracted. Molecular dynamics simulations indicated that this MEFA immunogen maintained a stable secondary structure and presented epitopes on the protein surface. Empirical data showed that mice immunized with the tagless CFA/I/II/IV MEFA developed strong antigen-specific antibody responses, and mouse serum antibodies significantly inhibited in vitro adherence of bacteria expressing these seven adhesins. These results revealed congruence of antigen immunogenicity between computational simulation and empirical mouse immunization and indicated this tag-less CFA/I/II/IV MEFA potentially an antigen for a broadly protective ETEC vaccine, suggesting a potential application of MEFA-based structural vaccinology for vaccine design against ETEC and likely other pathogens. PMID:28944092

Subcutaneous or oral immunization of mice with Lactococcus lactis expressing F4 fimbrial adhesin FaeG.

PubMed

Liu, Shujie; Li, Yongming; Xu, Ziwei; Wang, Yicheng

2013-01-01

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea in neonatal and postweaning piglets. Fimbrial adhesion of ETEC has been considered an important colonization factor with antigenicity. To safely and effectively deliver the F4 (K88) fimbrial adhesin FaeG to the immune system, we have previously constructed the secretory expression vector pNZ8112-faeG, and FaeG was produced in cytoplasmic form in Lactococcus lactis. In this work, BALB/c mice were immunized with recombinant L. lactis to further determine the immunogenicity of recombinant FaeG (rFaeG) via the subcutaneous or oral route. Subcutaneous immunization in mice with recombinant L. lactis induced a significant increase in the F4-specific serum IgG titer and the number of antibody-secreting cells (ASCs) in the spleen. Oral immunization of mice with recombinant L. lactis induced mucosal and systemic F4-specific immune responses and increased the number of ASCs in the spleen, mesenteric lymph nodes and Peyer's patches. High-dose (2.8 × 10(11) CFU) recombinant strains and adjuvant cholera toxin B subunit enhanced specific mucosal immune responses. The results suggest the feasibility of delivering rFaeG expressed in L. lactis to the immune system in order to induce an F4-specific immune response.

Molecular Characterization of Enterotoxin-Producing Escherichia coli Collected in 2011-2012, Russia.

PubMed

Kartsev, Nikolay N; Fursova, Nadezhda K; Pachkunov, Dmitry M; Bannov, Vasiliy A; Eruslanov, Boris V; Svetoch, Edward A; Dyatlov, Ivan A

2015-01-01

Enterotoxin-producing Escherichia coli (ETEC) are one of the main causative agents of diarrhea in children especially in developing countries and travel diarrhoea in adults. Pathogenic properties of ETEC associated with their ability to produce a heat-stable (ST) and/or heat-labile (LT) enterotoxins, as well as adhesins providing bacterial adhesion to intestinal epithelial cells. This study presents the molecular characterization of the ETEC isolates collected from the Central and Far-Eastern regions of Russia in 2011-2012. It was shown that all ETEC under study (n=18) had the heat-labile enterotoxin-coding operon elt, and had no the genes of the heat-stable enterotoxin operon est. DNA sequencing revealed two types of nucleotide exchanges in the eltB gene coding subunit B of LT in isolates collected from Cherepovets city (Central region, Russia) and Vladivostok city (Far-East region, Russia). Only one ETEC strain carried genes cfaA, cfaB, cfaC and cfaD coding adhesion factor CFA/I. Expression of LT in four ETEC isolates in the agglutination reaction was detected using a latex test-system. The isolates were assigned to serogroups O142 (n = 6), О6 (n = 4), О25 (n = 5), О26 (n = 2), and O115 (n = 1). Genotyping showed that they belonged to an earlier described sequence-type ST4 (n = 3) as well as to 11 novel sequence-types ST1043, ST1312, ST3697, ST3707, ST3708, ST3709, ST3710, ST3755, ST3756, ST3757 and ST4509. The ETEC isolates displayed different levels of antimicrobial resistance. Eight isolates were resistant to only one drug, three isolates-to two drugs, one isolate-to three drugs, two isolates-to four antibacterials, and only one isolate to each of the five, six and ten antibacterials simultaneously. Genetic determinants of the resistance to beta-lactams and other classes of antibacterials on the ETEC genomes were identified. There are blaTEM (n = 10), blaCTX-M-15 (n = 1), class 1 integron (n = 3) carrying resistance cassettes to aminoglycosides and sulphonamides dfrA17-aadA5 and dfrA12-orfF-aadA2. One isolate ETEC_Ef-6 was found to be a multidrug-resistant (MDR) pathogen that carried both the beta-lactamase gene and class 1 integron. These data suggest the circulation of ETEC in Russia. Further investigations are necessary to study the spread of the revealed ETEC sequence types (STs) and serotypes. Their role in the etiology of diarrhea should be also estimated.

Bromelain protects piglets from diarrhoea caused by oral challenge with K88 positive enterotoxigenic Escherichia coli

PubMed Central

Chandler, D; Mynott, T

1998-01-01

Background—K88 positive enterotoxigenic Escherichia coli (K88+ ETEC) is an important cause of diarrhoea in young piglets. K88+ ETEC pathogenesis relies on attachment to specific glycoprotein receptors located on the intestinal mucosa. Proteolytic treatment of these receptors in vitro and in vivo prevents attachment of K88+ ETEC to piglet small intestines and may be of clinical use to prevent K88+ ETEC pathogenesis. 
Aims—To determine whether bromelain, a proteolytic extract obtained from pineapple stems, would protect piglets against K88+ ETEC diarrhoea and to confirm and extend earlier findings on the effects of bromelain on K88+ ETEC receptors in vivo. 
Methods—Bromelain (0, 12.5, or 125 mg) was orally administered to just weaned piglets for 10 days. One day following commencement of bromelain treatment, piglets were challenged with K88+ ETEC (5 × 1010 K88ac:0149) for seven days. Intestinal contents from unchallenged piglets were obtained via an intestinal fistula, and tested for their ability to bind K88+ ETEC before and after bromelain treatment. 
Results—Both doses of bromelain were successful in reducing the incidence of K88+ ETEC diarrhoea and protected piglets from life threatening disease. Bromelain treated pigs also had significantly increased weight gain compared with untreated pigs. Bromelain only temporarily inhibited K88+ ETEC receptor activity, with receptor activity being regenerated 30 hours following treatment, consistent with the regeneration of new enterocytes. 
Conclusion—Results show that bromelain can temporarily inactivate ETEC receptors in vivo and protect against ETEC induced diarrhoea. Bromelain may therefore be an effective prophylaxis against ETEC infection. 

 Keywords: enterotoxigenic Escherichia coli; K88 ETEC; ETEC receptors; diarrhoea; bromelain PMID:10189844

Persistent Transmissible Gastroenteritis Virus Infection Enhances Enterotoxigenic Escherichia coli K88 Adhesion by Promoting Epithelial-Mesenchymal Transition in Intestinal Epithelial Cells.

PubMed

Xia, Lu; Dai, Lei; Yu, Qinghua; Yang, Qian

2017-11-01

Transmissible gastroenteritis virus (TGEV) is a coronavirus characterized by diarrhea and high morbidity rates, and the mortality rate is 100% in piglets less than 2 weeks old. Pigs infected with TGEV often suffer secondary infection by other pathogens, which aggravates the severity of diarrhea, but the mechanisms remain unknown. Here, we hypothesized that persistent TGEV infection stimulates the epithelial-mesenchymal transition (EMT), and thus enterotoxigenic Escherichia coli (ETEC) can more easily adhere to generating cells. Intestinal epithelial cells are the primary targets of TGEV and ETEC infections. We found that TGEV can persistently infect porcine intestinal columnar epithelial cells (IPEC-J2) and cause EMT, consistent with multiple changes in key cell characteristics. Infected cells display fibroblast-like shapes; exhibit increases in levels of mesenchymal markers with a corresponding loss of epithelial markers; have enhanced expression levels of interleukin-1β (IL-1β), IL-6, IL-8, transforming growth factor β (TGF-β), and tumor necrosis factor alpha (TNF-α) mRNAs; and demonstrate increases in migratory and invasive behaviors. Additional experiments showed that the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways via TGF-β is critical for the TGEV-mediated EMT process. Cellular uptake is also modified in cells that have undergone EMT. TGEV-infected cells have higher levels of integrin α5 and fibronectin and exhibit enhanced ETEC K88 adhesion. Reversal of EMT reduces ETEC K88 adhesion and inhibits the expression of integrin α5 and fibronectin. Overall, these results suggest that TGEV infection induces EMT in IPEC-J2 cells, increasing the adhesion of ETEC K88 in the intestine and facilitating dual infection. IMPORTANCE Transmissible gastroenteritis virus (TGEV) causes pig diarrhea and is often followed by secondary infection by other pathogens. In this study, we showed that persistent TGEV infection induces an EMT in porcine intestinal columnar epithelial cells (IPEC-J2) and enhances the adhesion of the secondary pathogen ETEC K88. Additional experiments suggest that integrin α5 and fibronectin play an important role in TGEV-enhanced ETEC K88 adhesion. Reversal of EMT reduces the expression of integrin α5 and fibronectin and also reduces ETEC K88 adhesion. We conclude that TGEV infection triggers EMT and facilitates dual infection. Our results provide new insights into secondary infection and suggest that targeted anti-EMT therapy may have implications for the prevention and treatment of secondary infection. Copyright © 2017 American Society for Microbiology.

Lactobacillus acidophilus alleviates the inflammatory response to enterotoxigenic Escherichia coli K88 via inhibition of the NF-κB and p38 mitogen-activated protein kinase signaling pathways in piglets.

PubMed

Li, Haihua; Zhang, Lei; Chen, Longbin; Zhu, Qi; Wang, Wenjie; Qiao, Jiayun

2016-11-10

A newly isolated L. acidophilus strain has been reported to have potential anti-inflammatory activities against lipopolysaccharide (LPS) challenge in piglet, while the details of the related inflammatory responses are limited. Here we aimed to analysis the ability of L. acidophilus to regulate inflammatory responses and to elucidate the mechanisms involved in its anti-inflammatory activity. The ETEC (enterotoxigenic Escherichia coli) K88-induced up-regulations of IL-1β, IL-8 and TNF-α were obviously inhibited by L. acidophilus while IL-10 was significantly increased. Moreover, L. acidophilus down-regulated pattern recognition receptors TLR (Toll-like receptor) 2 and TLR4 expression in both spleen and mesenteric lymph nodes of ETEC-challenged piglets, in accompanied with the reduced phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and mitogen-activated protein kinase (MAPK) p38 as well in spleen of ETEC-infected piglets. Furthermore, L.acidophilus significantly increased the expression of the negative regulators of TLRs signaling, including Tollip, IRAK-M, A20 and Bcl-3 in spleen of ETEC-challenged piglets. Our findings suggested that L. acidophilus regulated inflammatory response to ETEC via impairing both NF-κB and MAPK signaling pathways in piglets.

Antibacterial activity of silver and zinc nanoparticles against Vibrio cholerae and enterotoxic Escherichia coli

PubMed Central

Salem, Wesam; Leitner, Deborah R.; Zingl, Franz G.; Schratter, Gebhart; Prassl, Ruth; Goessler, Walter; Reidl, Joachim; Schild, Stefan

2015-01-01

Vibrio cholerae and enterotoxic Escherichia coli (ETEC) remain two dominant bacterial causes of severe secretory diarrhea and still a significant cause of death, especially in developing countries. In order to investigate new effective and inexpensive therapeutic approaches, we analyzed nanoparticles synthesized by a green approach using corresponding salt (silver or zinc nitrate) with aqueous extract of Caltropis procera fruit or leaves. We characterized the quantity and quality of nanoparticles by UV–visible wavelength scans and nanoparticle tracking analysis. Nanoparticles could be synthesized in reproducible yields of approximately 108 particles/ml with mode particles sizes of approx. 90–100 nm. Antibacterial activity against two pathogens was assessed by minimal inhibitory concentration assays and survival curves. Both pathogens exhibited similar resistance profiles with minimal inhibitory concentrations ranging between 5 × 105 and 107 particles/ml. Interestingly, zinc nanoparticles showed a slightly higher efficacy, but sublethal concentrations caused adverse effects and resulted in increased biofilm formation of V. cholerae. Using the expression levels of the outer membrane porin OmpT as an indicator for cAMP levels, our results suggest that zinc nanoparticles inhibit adenylyl cyclase activity. This consequently deceases the levels of this second messenger, which is a known inhibitor of biofilm formation. Finally, we demonstrated that a single oral administration of silver nanoparticles to infant mice colonized with V. cholerae or ETEC significantly reduces the colonization rates of the pathogens by 75- or 100-fold, respectively. PMID:25466205

Effects of dietary live yeast supplementation on growth performance, diarrhoea severity, intestinal permeability and immunological parameters of weaned piglets challenged with enterotoxigenic Escherichia coli K88.

PubMed

Che, Lianqiang; Xu, Qin; Wu, Cheng; Luo, Yuheng; Huang, Xiaobo; Zhang, Bo; Auclair, Eric; Kiros, Tadele; Fang, Zhengfeng; Lin, Yan; Xu, Shengyu; Feng, Bin; Li, Jian; Wu, De

2017-12-01

This study aimed to investigate the effects of dietary live yeast (LY) supplementation on growth, intestinal permeability and immunological parameters of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Piglets weaned at 21 d were allocated into three treatments with six pens and six piglets per pen, receiving the control diet (CON), diets supplemented with antibiotics plus zinc oxide (ANT-ZnO) and LY (Saccharomyces cerevisiae strain CNCM I-4407), respectively, for a period of 2 weeks. On day 8, thirty-six piglets were selected as control without ETEC (CON), CON-ETEC, ANT-ZnO-ETEC and LY-ETEC groups challenged with ETEC until day 10 for sample collections. Piglets fed ANT-ZnO diet had the highest average daily gain and average daily feed intake (P<0·05) during the 1st week, but ADG of piglets fed the ANT-ZnO diet was similar as piglets fed LY diet during the second week. Piglets with LY-ETEC or ANT-ZnO-ETEC had markedly lower diarrhoea score (P<0·05) than piglets with CON-ETEC during the 24 h after ETEC challenge. Relative to piglets with CON, the counts of E. coli, urinary ratio of lactulose to mannitol, plasma IL-6 concentration, mRNA abundances of innate immunity-related genes in ileum and mesenteric lymph node tissues were increased (P<0·05), whereas the villous height of jejunum and relative protein expression of ileum claudin-1 were decreased (P<0·05) in piglets with CON-ETEC; however, these parameters did not markedly change in piglets with LY-ETEC or ANT-ZnO-ETEC. In summary, dietary LY supplementation could alleviate the severity of diarrhoea in piglets with ETEC, which may be associated with the improved permeability, innate immunity and bacterial profile.

Presence of enterotoxigenic Escherichia coli in biofilms formed in water containers in poor households coincides with epidemic seasons in Dhaka.

PubMed

Ahmed, D; Islam, M S; Begum, Y A; Janzon, A; Qadri, F; Sjöling, A

2013-04-01

The objective of this study was to investigate if biofilms may be potential reservoirs for the waterborne pathogen enterotoxigenic Escherichia coli (ETEC) in household water in Dhaka, Bangladesh. Biofilms formed on submerged glass slides. Mature biofilms were found significantly more often on glass slides collected in the monsoon period between the two annual ETEC peaks in Bangladesh, that is, between May and August than the rest of the year (P < 0.03). Sixty-four per cent (49/77) of all biofilms analysed by quantitative real-time PCR were positive for ETEC. Significantly more ETEC-PCR positive biofilms were found during the epidemic peaks and during flooding periods than the rest of the year (P < 0.008). Planktonic ETEC was present in the household water during all seasons, but there was no correlation between presence or numbers of ETEC in water and the epidemic peaks. We conclude that ETEC is continuously present in water and biofilms in household water reservoirs in Dhaka, which has a high prevalence of ETEC diarrhoea. The frequency of biofilms with ETEC was significantly associated (P < 0.008) with seasonal epidemic peaks of ETEC diarrhoea. We show for the first time that enterotoxigenic Escherichia coli (ETEC), the causative agent of acute watery diarrhoea and travellers' diarrhoea is present in biofilms in household water tanks in Dhaka, Bangladesh. © 2012 The Society for Applied Microbiology.

Virulence factors, pathogenesis and vaccine protection in cholera and ETEC diarrhea.

PubMed

Sánchez, Joaquín; Holmgren, Jan

2005-08-01

Recent work has provided new insights into the pathogenesis of the potentially life-threatening diarrheas caused by Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC): a new mechanism (post-translational degradation), which is involved in the control of cholera toxin expression, has been discovered. Recent evidence also suggests that vibrios upregulate cholera toxin expression in response to intestinal fluid components, and enterotoxin-carrying bacterial outer membrane vesicles might have a function in ETEC pathogenesis. An important role of the environment is supported by the correlation between cholera incidence and elevated sea surface temperature, which supports the notion that the zooplankton is a V. cholerae reservoir. Additionally, environmental lytic cholera phages could influence cholera seasonality by 'terminating' the seasonal epidemic. Finally, the strong herd immunity elicited by an oral cholera vaccine indicates that cholera vaccination could have a significant public health impact.

Antibacterial activity of silver and zinc nanoparticles against Vibrio cholerae and enterotoxic Escherichia coli.

PubMed

Salem, Wesam; Leitner, Deborah R; Zingl, Franz G; Schratter, Gebhart; Prassl, Ruth; Goessler, Walter; Reidl, Joachim; Schild, Stefan

2015-01-01

Vibrio cholerae and enterotoxic Escherichia coli (ETEC) remain two dominant bacterial causes of severe secretory diarrhea and still a significant cause of death, especially in developing countries. In order to investigate new effective and inexpensive therapeutic approaches, we analyzed nanoparticles synthesized by a green approach using corresponding salt (silver or zinc nitrate) with aqueous extract of Caltropis procera fruit or leaves. We characterized the quantity and quality of nanoparticles by UV-visible wavelength scans and nanoparticle tracking analysis. Nanoparticles could be synthesized in reproducible yields of approximately 10(8) particles/ml with mode particles sizes of approx. 90-100 nm. Antibacterial activity against two pathogens was assessed by minimal inhibitory concentration assays and survival curves. Both pathogens exhibited similar resistance profiles with minimal inhibitory concentrations ranging between 5×10(5) and 10(7) particles/ml. Interestingly, zinc nanoparticles showed a slightly higher efficacy, but sublethal concentrations caused adverse effects and resulted in increased biofilm formation of V. cholerae. Using the expression levels of the outer membrane porin OmpT as an indicator for cAMP levels, our results suggest that zinc nanoparticles inhibit adenylyl cyclase activity. This consequently deceases the levels of this second messenger, which is a known inhibitor of biofilm formation. Finally, we demonstrated that a single oral administration of silver nanoparticles to infant mice colonized with V. cholerae or ETEC significantly reduces the colonization rates of the pathogens by 75- or 100-fold, respectively. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.

Divergence of actual and reference evapotranspiration observations for irrigated sugarcane with windy tropical conditions

NASA Astrophysics Data System (ADS)

Anderson, R. G.; Wang, D.; Tirado-Corbalá, R.; Zhang, H.; Ayars, J. E.

2015-01-01

Standardized reference evapotranspiration (ET) and ecosystem-specific vegetation coefficients are frequently used to estimate actual ET. However, equations for calculating reference ET have not been well validated in tropical environments. We measured ET (ETEC) using eddy covariance (EC) towers at two irrigated sugarcane fields on the leeward (dry) side of Maui, Hawaii, USA in contrasting climates. We calculated reference ET at the fields using the short (ET0) and tall (ETr) vegetation versions of the American Society for Civil Engineers (ASCE) equation. The ASCE equations were compared to the Priestley-Taylor ET (ETPT) and ETEC. Reference ET from the ASCE approaches exceeded ETEC during the mid-period (when vegetation coefficients suggest ETEC should exceed reference ET). At the windier tower site, cumulative ETr exceeded ETEC by 854 mm over the course of the mid-period (267 days). At the less windy site, mid-period ETr still exceeded ETEC, but the difference was smaller (443 mm). At both sites, ETPT approximated mid-period ETEC more closely than the ASCE equations ((ETPT-ETEC) < 170 mm). Analysis of applied water and precipitation, soil moisture, leaf stomatal resistance, and canopy cover suggest that the lower observed ETEC was not the result of water stress or reduced vegetation cover. Use of a custom-calibrated bulk canopy resistance improved the reference ET estimate and reduced seasonal ET discrepancy relative to ETPT and ETEC in the less windy field and had mixed performance in the windier field. These divergences suggest that modifications to reference ET equations may be warranted in some tropical regions.

Divergence of reference evapotranspiration observations with windy tropical conditions

NASA Astrophysics Data System (ADS)

Anderson, R. G.; Wang, D.; Tirado-Corbalá, R.; Zhang, H.; Ayars, J. E.

2014-06-01

Standardized reference evapotranspiration (ET) and ecosystem-specific vegetation coefficients are frequently used to estimate actual ET. However, equations for calculating reference ET have not been well validated in tropical environments. We measured ET (ETEC) using Eddy Covariance (EC) towers at two irrigated sugarcane fields on the leeward (dry) side of Maui, Hawaii, USA in contrasting climates. We calculated reference ET at the fields using the short (ET0) and tall (ETr) vegetation versions of the American Society for Civil Engineers (ASCE) equation. The ASCE equations were compared to the Priestley-Taylor ET (ETPT) and ETEC. Reference ET from the ASCE approaches exceeded ETEC during the mid-period (when vegetation coefficients suggest ETEC should exceed reference ET). At the windier tower site, cumulative ETr exceeded ETEC by 854 mm over the course of the mid-period (267 days). At the less windy site, mid-period ETr still exceeded ETEC, but the difference was smaller (443 mm). At both sites, ETPT approximated mid-period ETEC more closely than the ASCE equations ((ETPT-ETEC) < 170 mm). Analysis of applied water and precipitation, soil moisture, leaf stomatal resistance, and canopy cover suggest that the lower observed ETEC was not the result of water stress or reduced vegetation cover. Use of a custom calibrated bulk canopy resistance improved the reference ET estimate and reduced seasonal ET discrepancy relative to ETPT and ETEC for the less windy field and had mixed performance at the windier field. These divergences suggest that modifications to reference ET equations may be warranted in some tropical regions.

Lactulose and Lactobacillus plantarum, a Potential Complementary Synbiotic To Control Postweaning Colibacillosis in Piglets

PubMed Central

Guerra-Ordaz, A. A.; González-Ortiz, G.; La Ragione, R. M.; Woodward, M. J.; Collins, J. W.; Pérez, J. F.

2014-01-01

The potential of a prebiotic oligosaccharide lactulose, a probiotic strain of Lactobacillus plantarum, or their synbiotic combination to control postweaning colibacillosis in pigs was evaluated using an enterotoxigenic Escherichia coli (ETEC) K88 oral challenge. Seventy-two weanlings were fed four diets: a control diet (CTR), that diet supplemented with L. plantarum (2 × 1010 CFU · day−1) (LPN), that diet supplemented with 10 g · kg−1 lactulose (LAC), or a combination of the two treatments (SYN). After 7 days, the pigs were orally challenged. Six pigs per treatment were euthanized on days 6 and 10 postchallenge (PC). Inclusion of lactulose improved the average daily gain (ADG) (P < 0.05) and increased lactobacilli (P < 0.05) and the percentage of butyric acid (P < 0.02) in the colon. An increase in the ileum villous height (P < 0.05) and a reduction of the pig major acute-phase protein (Pig-MAP) in serum (P < 0.01) were observed also. The inclusion of the probiotic increased numbers of L. plantarum bacteria in the ileum and colon (P < 0.05) and in the total lactobacilli in the colon and showed a trend to reduce diarrhea (P = 0.09). The concentrations of ammonia in ileal and colonic digesta were decreased (P < 0.05), and the villous height (P < 0.01) and number of ileal goblet cells (P < 0.05) increased, at day 10 PC. A decrease in plasmatic tumor necrosis factor alpha (TNF-α) (P < 0.01) was also seen. The positive effects of the two additives were combined in the SYN treatment, resulting in a complementary synbiotic with potential to be used to control postweaning colibacillosis. PMID:24907322

Impact of lower challenge doses of enterotoxigenic Escherichia coli on clinical outcome, intestinal colonization and immune responses in adult volunteers.

PubMed

Chakraborty, Subhra; Harro, Clayton; DeNearing, Barbara; Brubaker, Jessica; Connor, Sean; Maier, Nicole; Dally, Len; Flores, Jorge; Bourgeois, A Louis; Walker, Richard; Sack, David A

2018-04-01

A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60-70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. ClinicalTrials.gov NCT00844493.

Impact of lower challenge doses of enterotoxigenic Escherichia coli on clinical outcome, intestinal colonization and immune responses in adult volunteers

PubMed Central

DeNearing, Barbara; Brubaker, Jessica; Connor, Sean; Maier, Nicole; Dally, Len; Flores, Jorge; Bourgeois, A. Louis; Walker, Richard; Sack, David A.

2018-01-01

A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60–70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. Trial registration: ClinicalTrials.gov NCT00844493. PMID:29702652

Efficacy of a single oral dose of a live bivalent E. coli vaccine against post-weaning diarrhea due to F4 and F18-positive enterotoxigenic E. coli.

PubMed

Nadeau, É; Fairbrother, J M; Zentek, J; Bélanger, L; Tremblay, D; Tremblay, C-L; Röhe, I; Vahjen, W; Brunelle, M; Hellmann, K; Cvejić, D; Brunner, B; Schneider, C; Bauer, K; Wolf, R; Hidalgo, Á

2017-08-01

F4- and F18-positive enterotoxigenic E. coli strains (F4-ETEC and F18-ETEC) are important causes of post-weaning diarrhea (PWD) in pigs. F4 (antigenic variant ac) and F18 (ab and ac) fimbriae are major antigens that play an important role in the early stages of infection. Herein, the efficacy of a live oral vaccine consisting of two non-pathogenic E. coli strains, one F4ac- and one F18ac-positive, was evaluated using F4ac-ETEC and F18ab-ETEC challenge models. A randomized, masked, placebo-controlled, block design, parallel-group confirmatory study with two different vaccination-challenge intervals (7 and 21 days) was conducted for each challenge model. The vaccine was administered in one dose, to ≥18-day-old piglets via drinking water. Efficacy was assessed by evaluating diarrhea, clinical observations, weight gain and fecal shedding of F4-ETEC or F18-ETEC. Anti-F4 and anti-F18 immunoglobulins in blood were measured. The vaccination resulted in significant reductions in clinical PWD and fecal shedding of F4-ETEC and F18-ETEC after the 7- and 21-day-post-vaccination heterologous challenges, except for after the 21-day-post-vaccination F4-ETEC challenge, when the clinical PWD was too mild to demonstrate efficacy. A significant reduction of mortality and weight loss by vaccination were observed following the F18-ETEC challenge. The 7-day protection was associated with induction of anti-F4 and anti-F18 IgM, whereas the 21-day protection was mainly associated with anti-F4 and anti-F18 IgA. The 7-day onset and 21-day duration of protection induced by this vaccine administered once in drinking water to pigs of at least 18days of age were confirmed by protection against F4-ETEC and F18-ETEC, and induction of F4 and F18-specific immunity. Cross protection of the vaccine against F18ab-E. coli was demonstrated for both the 7- and 21-day F18-ETEC challenges. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dietary addition of Lactobacillus rhamnosus GG impairs the health of Escherichia coli F4-challenged piglets.

PubMed

Trevisi, P; Casini, L; Coloretti, F; Mazzoni, M; Merialdi, G; Bosi, P

2011-08-01

Lactobacillus rhamnosus GG (LGG) is a probiotic for humans and is normally not found in pigs; however, it has been shown to protect the human-derived intestinal Caco-2 cells against the damage induced by an important intestinal pathogen, enterotoxigenic Escherichia coli F4 (ETEC). An experiment was conducted to test whether the dietary addition of LGG improves the growth and health of weaned pigs when orally challenged by E. coli F4. Thirty-six pigs were weaned at 21 days and assigned to a standard weaning diet with or without 1010 CFU LGG (ATCC 53103) per day. The pigs, individually penned, were orally challenged with 1.5 ml of a 1010 CFU E. coli F4 suspension on day 7 and slaughtered on day 12 or 14. With the addition of LGG, the average daily gain and the average daily feed intake were reduced after the challenge with ETEC and for the entire trial (P < 0.05). The average faecal score tended to worsen from day 11 to the end of the trial and the concentration of ETEC in the faeces tended to increase (P = 0.07) with the LGG supplementation. The counts of lactic acid bacteria, enterobacteria and yeasts in the colonic digesta were not affected. The pH values in ileal, colonic and caecal digesta, and the small intestine size were also unchanged. Regardless of the site of measurement (duodenum, jejunum or ileum), a trend of decreased villus height was seen with LGG (P = 0.10). Crypt depth and villus to crypt ratio were unchanged by the diet. A gradual increase of total seric IgA was seen after 1 week and after the challenge, in the control (P < 0.05), but not in the treated group. After the challenge, the LGG reduced the total IgA in the blood serum (P < 0.05), v. the control. The total IgA in the saliva and in the jejunum secretion were not affected by the diet. The F4-specific IgA activity was not affected by the diet at all the samplings. Our result shows that, the administration of LGG do not prevent or reduce the detrimental effect of the E. coli F4 infection on the growth performance and health status of weaned piglet.

New perspectives to the enterotoxigenic E. coli F4 porcine infection model: Susceptibility genotypes in relation to performance, diarrhoea and bacterial shedding.

PubMed

Roubos-van den Hil, Petra J; Litjens, Ralph; Oudshoorn, Anna-Katharina; Resink, Jan Willem; Smits, Coen H M

2017-04-01

Enterotoxigenic E. coli (ETEC), causing post-weaning diarrhoea, is a major problem in weaned piglets. Individual animal responses to ETEC infection show high variability in animal experiments. Two studies were designed to optimize the ETEC F4ac infection model in piglets by combining the genotype susceptibility with performance, diarrhoea incidence and bacterial shedding. The studies were performed with respectively 120 and 80 male piglets that were tested for susceptibility or resistance towards ETEC O149:F4ac by a DNA marker based test. Three different genotypes were observed; resistant (RR), susceptible heterozygote (RS) and susceptible homozygote (SS). Piglets, were orally infected with an inoculum suspension (containing 1.5E8 CFU/ml ETEC F4ac) at day 0, 1 and 2 of the study. Performance, diarrhoea incidence and bacterial shedding were followed for 21days. In the first week after challenge a difference in average daily gain was observed between resistant and susceptible piglets in both studies. For the complete study period no significant differences were observed. Diarrhoea incidence was significantly higher in susceptible pigs compared to the resistant pigs in the first week after challenge. Bacterial shedding was much higher in the susceptible pigs and ETEC excretion lasted longer. ETEC was hardly detected in the faecal material of the resistant pigs. In conclusion, susceptible pigs showed higher diarrhoea incidence and higher numbers of faecal ETEC shedding in the first week after challenge compared to resistant pigs. The DNA marker based test can be used to select pigs that are susceptible for ETEC for inclusion in ETEC infection model, resulting in less animals needed to perform infection studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative analysis of antimicrobial resistance in enterotoxigenic Escherichia coli isolates from two paediatric cohort studies in Lima, Peru

PubMed Central

Medina, Anicia M.; Rivera, Fulton P.; Pons, Maria J.; Riveros, Maribel; Gomes, Cláudia; Bernal, María; Meza, Rina; Maves, Ryan C.; Huicho, Luis; Chea-Woo, Elsa; Lanata, Claudio F.; Gil, Ana I.; Ochoa, Theresa J.; Ruiz, Joaquim

2015-01-01

Background Antibiotic resistance is increasing worldwide, being of special concern in low- and middle-income countries. The aim of this study was to determine the antimicrobial susceptibility and mechanisms of resistance in 205 enterotoxigenic Escherichia coli (ETEC) isolates from two cohort studies in children <24 months in Lima, Peru. Methods ETEC were identified by an in-house multiplex real-time PCR. Susceptibility to 13 antimicrobial agents was tested by disk diffusion; mechanisms of resistance were evaluated by PCR. Results ETEC isolates were resistant to ampicillin (64%), cotrimoxazole (52%), tetracycline (37%); 39% of the isolates were multidrug-resistant. Heat-stable toxin producing (ETEC-st) (48%) and heat-labile toxin producing ETEC (ETEC-lt) (40%) had higher rates of multidrug resistance than isolates producing both toxins (ETEC-lt-st) (21%), p<0.05. Only 10% of isolates were resistant to nalidixic acid and none to ciprofloxacin or cefotaxime. Ampicillin and sulfamethoxazole resistance were most often associated with blaTEM (69%) and sul2 genes (68%), respectively. Tetracycline resistance was associated with tet(A) (49%) and tet(B) (39%) genes. Azithromycin inhibitory diameters were ≤15 mm in 36% of isolates, with 5% of those presenting the mph(A) gene. Conclusions ETEC from Peruvian children are often resistant to older, inexpensive antibiotics, while remaining susceptible to ciprofloxacin, cephalosporins and furazolidone. Fluoroquinolones and azithromycin remain the drugs of choice for ETEC infections in Peru. However, further development of resistance should be closely monitored. PMID:26175267

Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea.

PubMed

Ahmed, Tanvir; Bhuiyan, Taufiqur R; Zaman, K; Sinclair, David; Qadri, Firdausi

2013-07-05

Infection with enterotoxigenic Escherichia coli (ETEC) bacteria is a common cause of diarrhoea in adults and children in developing countries and is a major cause of 'travellers' diarrhoea' in people visiting or returning from endemic regions. A killed whole cell vaccine (Dukoral®), primarily designed and licensed to prevent cholera, has been recommended by some groups to prevent travellers' diarrhoea in people visiting endemic regions. This vaccine contains a recombinant B subunit of the cholera toxin that is antigenically similar to the heat labile toxin of ETEC. This review aims to evaluate the clinical efficacy of this vaccine and other vaccines designed specifically to protect people against diarrhoea caused by ETEC infection. To evaluate the efficacy, safety, and immunogenicity of vaccines for preventing ETEC diarrhoea. We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and http://clinicaltrials.gov up to December 2012. Randomized controlled trials (RCTs) and quasi-RCTs comparing use of vaccines to prevent ETEC with use of no intervention, a control vaccine (either an inert vaccine or a vaccine normally given to prevent an unrelated infection), an alternative ETEC vaccine, or a different dose or schedule of the same ETEC vaccine in healthy adults and children living in endemic regions, intending to travel to endemic regions, or volunteering to receive an artificial challenge of ETEC bacteria. Two authors independently assessed each trial for eligibility and risk of bias. Two independent reviewers extracted data from the included studies and analyzed the data using Review Manager (RevMan) software. We reported outcomes as risk ratios (RR) with 95% confidence intervals (CI). We assessed the quality of the evidence using the GRADE approach. Twenty-four RCTs, including 53,247 participants, met the inclusion criteria. Four studies assessed the protective efficacy of oral cholera vaccines when used to prevent diarrhoea due to ETEC and seven studies assessed the protective efficacy of ETEC-specific vaccines. Of these 11 studies, seven studies presented efficacy data from field trials and four studies presented efficacy data from artificial challenge studies. An additional 13 trials contributed safety and immunological data only. Cholera vaccinesThe currently available, oral cholera killed whole cell vaccine (Dukoral®) was evaluated for protection of people against 'travellers' diarrhoea' in a single RCT in people arriving in Mexico from the USA. We did not identify any statistically significant effects on ETEC diarrhoea or all-cause diarrhoea (one trial, 502 participants, low quality evidence).Two earlier trials, one undertaken in an endemic population in Bangladesh and one undertaken in people travelling from Finland to Morocco, evaluated a precursor of this vaccine containing purified cholera toxin B subunit rather than the recombinant subunit in Dukoral®. Short term protective efficacy against ETEC diarrhoea was demonstrated, lasting for around three months (RR 0.43, 95% CI 0.26 to 0.71; two trials, 50,227 participants). This vaccine is no longer available. ETEC vaccinesAn ETEC-specific, killed whole cell vaccine, which also contains the recombinant cholera toxin B-subunit, was evaluated in people travelling from the USA to Mexico or Guatemala, and from Austria to Latin America, Africa, or Asia. We did not identify any statistically significant differences in ETEC-specific diarrhoea or all-cause diarrhoea (two trials, 799 participants), and the vaccine was associated with increased vomiting (RR 2.0, 95% CI 1.16 to 3.45; nine trials, 1528 participants). The other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits. There is currently insufficient evidence from RCTs to support the use of the oral cholera vaccine Dukoral® for protecting travellers against ETEC diarrhoea. Further research is needed to develop safe and effective vaccines to provide both short and long-term protection against ETEC diarrhoea.

Fermented soya bean (tempe) extracts reduce adhesion of enterotoxigenic Escherichia coli to intestinal epithelial cells.

PubMed

Roubos-van den Hil, P J; Nout, M J R; Beumer, R R; van der Meulen, J; Zwietering, M H

2009-03-01

This study aimed to investigate the effect of processed soya bean, during the successive stages of tempe fermentation and different fermentation times, on adhesion of enterotoxigenic Escherichia coli (ETEC) K88 to intestinal brush border cells as well as Caco-2 intestinal epithelial cells; and to clarify the mechanism of action. Tempe was prepared at controlled laboratory scale using Rhizopus microsporus var. microsporus as the inoculum. Extracts of raw, soaked and cooked soya beans reduced ETEC adhesion to brush border cells by 40%. Tempe extracts reduced adhesion by 80% or more. ETEC adhesion to Caco-2 cells reduced by 50% in the presence of tempe extracts. ETEC K88 bacteria were found to interact with soya bean extracts, and this may contribute to the observed decrease of ETEC adhesion to intestinal epithelial cells. Fermented soya beans (tempe) reduce the adhesion of ETEC to intestinal epithelial cells of pig and human origin. This reduced adhesion is caused by an interaction between ETEC K88 bacteria and soya bean compounds. The results strengthen previous observations on the anti-diarrhoeal effect of tempe. This effect indicates that soya-derived compounds may reduce adhesion of ETEC to intestinal cells in pigs as well as in humans and prevent against diarrhoeal diseases.

Development and accuracy of quantitative real-time polymerase chain reaction assays for detection and quantification of enterotoxigenic Escherichia coli (ETEC) heat labile and heat stable toxin genes in travelers' diarrhea samples.

PubMed

Youmans, Bonnie P; Ajami, Nadim J; Jiang, Zhi-Dong; Petrosino, Joseph F; DuPont, Herbert L; Highlander, Sarah K

2014-01-01

Enterotoxigenic Escherichia coli (ETEC), the leading bacterial pathogen of travelers' diarrhea, is routinely detected by an established DNA hybridization protocol that is neither sensitive nor quantitative. Quantitative real-time polymerase chain reaction (qPCR) assays that detect the ETEC toxin genes eltA, sta1, and sta2 in clinical stool samples were developed and tested using donor stool inoculated with known quantities of ETEC bacteria. The sensitivity of the qPCR assays is 89%, compared with 22% for the DNA hybridization assay, and the limits of detection are 10,000-fold lower than the DNA hybridization assays performed in parallel. Ninety-three clinical stool samples, previously characterized by DNA hybridization, were tested using the new ETEC qPCR assays. Discordant toxin profiles were observed for 22 samples, notably, four samples originally typed as ETEC negative were ETEC positive. The qPCR assays are unique in their sensitivity and ability to quantify the three toxin genes in clinical stool samples.

Stimulation of mucosal immune response following oral administration of enterotoxigenic Escherichia coli fimbriae (CFA/I) entrapped in liposomes in conjunction with inactivated whole-cell Vibrio cholerae vaccine.

PubMed

Dima, V F; Ionescu, M D; Palade, R; Balotescu, C; Becheanu, G; Dima, S V

2001-01-01

In this study, we have searched for an effective mucosal vaccine. An oral enterotoxigenic E. coli vaccine containing colonization factor antigen (CFA/I) associated with inactivated whole-cell V. cholerae vaccine (WCV) has been tested for safety and immunogenicity in animals. Five groups of animals were used. The results showed the following: (a) vaccine containing CFA/I antigen entrapped in liposomes and associated with WCV (batch C) had increased titers of specific antibodies to CFA/I antigen in 15 to 18 (83.3%) animals; (b) specific Peyer's patches (PP), lymph nodes (LN) and spleen (SPL) lymphocytes proliferation was detected following in vitro restimulation with CFA/I antigen or WCV. This response gradually increased to the highest value by the 35th postimmunization day. Moreover, lower PP, LN and spleen (SPL) proliferation was observed in rabbits receiving soluble CFA/I antigen (S-CFA/I) or free liposomes (F-L) alone; (c) adhesion of E. coli H10407 strain labelled with 3H-leucine in immunized and control animals revealed the following local effects: (i) protection of rabbit intestinal mucosa against virulent E. coli cells; (ii) inhibition of adhesion of ETEC bacteria to intestinal mucosa and (iii) significantly faster release of E. coli H 10407 strain labelled with 3H-leucine from the intestinal tract of immunized animals. The histopathological and electron microscope findings confirmed the above results. The experimental results point out an efficient protection against infection with E. coli strains (ETEC), after mucosal vaccination with CFA/I antigen entrapped in liposomes associated with inactivated whole-cell Vibrio cholerae as immunological adjuvant.

Human experimental challenge with enterotoxigenic Escherichia coli elicits immune responses to canonical and novel antigens relevant to vaccine development.

PubMed

Chakraborty, Subhra; Randall, Arlo; Vickers, Tim J; Molina, Doug; Harro, Clayton D; DeNearing, Barbara; Brubaker, Jessica; Sack, David A; Bourgeois, A Louis; Felgner, Philip L; Liang, Xiaowu; Mani, Sachin; Wenzel, Heather; Townsend, R Reid; Gilmore, Petra E; Darsley, Michael J; Rasko, David A; Fleckenstein, James M

2018-05-24

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal illness in the developing world. ETEC vaccinology has been challenged by genetic diversity and heterogeneity of canonical antigens. Examination of the antigenic breadth of immune responses associated with protective immunity could afford new avenues for vaccine development. Antibody lymphocyte supernatants (ALS) and sera from 20 naïve human volunteers challenged with ETEC strain H10407 and from 10 volunteers re-challenged 4-6 weeks later with the same strain (9 of whom were completely protected on re-challenge) were tested against ETEC proteome microarrays containing 957 antigens. ETEC challenge stimulated robust serum and mucosal (ALS) responses to canonical vaccine antigens (CFA/I, and the B subunit of LT) as well as a small number of antigens not presently targeted in ETEC vaccines. These included pathovar-specific secreted proteins (EtpA, EatA) as well as highly conserved E. coli antigens including YghJ, flagellin (FliC), and pertactin-like autotransporter proteins, all of which have previously afforded protection against ETEC infection in preclinical studies. Collectively, studies reported here suggest that immune responses following ETEC infection involve traditional vaccine targets as well as a select number of more recently identified protein antigens that could offer additional avenues for vaccine development for these pathogens.

The fecal presence of enterotoxin and F4 genes as an indicator of efficacy of treatment with colistin sulfate in pigs.

PubMed

Rhouma, Mohamed; Fairbrother, John Morris; Thériault, William; Beaudry, Francis; Bergeron, Nadia; Laurent-Lewandowski, Sylvette; Letellier, Ann

2017-01-05

Enterotoxigenic Escherichia coli (ETEC) strains producing multiple enterotoxins are important causes of post-weaning diarrhea (PWD) in pigs. The aim of the present study was to investigate the fecal presence of ETEC enterotoxin as well as F4 and F18 genes as an indicator of colistin sulfate (CS) efficacy for treatment of PWD in pigs. Forty-eight piglets were weaned at the age of 21 days, and were divided into four groups: challenged treated, challenged untreated, unchallenged treated, and unchallenged untreated. Challenge was performed using 10 9  CFU of an ETEC: F4 strain, and treatment was conducted using oral CS at the dose of 50,000 IU/kg. The fecal presence of genes encoding for STa, STb, LT, F4 and F18 was detected using PCR. The PCR amplification of ETEC virulence genes showed that nearly 100% of pigs excreted genes encoding for STa and STb toxins in the feces before the challenge. These genes, in the absence of the gene encoding F4, were considered as a marker for F4-negative ETEC. One day after ETEC: F4 oral challenge pigs in the two challenged groups excreted the genes encoding LT and F4 in the feces. These genes were considered as a marker for F4-positive ETEC. However, the gene encoding F18 was not detected in any fecal samples of the 4 groups throughout the experiment. After only 3 days of successive oral treatment with CS, a significant reduction in both the F4-positive and negative ETEC populations was observed in the challenged treated group compared to the challenged untreated group (p < 0.0001). Our study is among the first to report that under controlled farming conditions, oral CS treatment had a significant effect on both fecal F4-positive and F4-negative ETEC in pigs. However, CS clinical efficiency was correlated with non-detection of F4-positive ETEC in the feces. Furthermore the fecal presence of F4-negative ETEC was not associated with clinical symptoms of post-weaning diarrhea in pigs.

F4+ ETEC infection and oral immunization with F4 fimbriae elicits an IL-17-dominated immune response.

PubMed

Luo, Yu; Van Nguyen, Ut; de la Fe Rodriguez, Pedro Y; Devriendt, Bert; Cox, Eric

2015-10-21

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. Porcine-specific ETEC strains possess different fimbrial subtypes of which F4 fimbriae are the most frequently associated with ETEC-induced diarrhea in piglets. These F4 fimbriae are potent oral immunogens that induce protective F4-specific IgA antibody secreting cells at intestinal tissues. Recently, T-helper 17 (Th17) cells have been implicated in the protection of the host against extracellular pathogens. However, it remains unknown if Th17 effector responses are needed to clear ETEC infections. In the present study, we aimed to elucidate if ETEC elicits a Th17 response in piglets and if F4 fimbriae trigger a similar response. F4(+) ETEC infection upregulated IL-17A, IL-17F, IL-21 and IL-23p19, but not IL-12 and IFN-γ mRNA expression in the systemic and mucosal immune system. Similarly, oral immunization with F4 fimbriae triggered a Th17 signature evidenced by an upregulated mRNA expression of IL-17F, RORγt, IL-23p19 and IL-21 in the peripheral blood mononuclear cells (PBMCs). Intriguingly, IL-17A mRNA levels were unaltered. To further evaluate this difference between systemic and mucosal immune responses, we assayed the cytokine mRNA profile of F4 fimbriae stimulated PBMCs. F4 fimbriae induced IL-17A, IL-17F, IL-22 and IL-23p19, but downregulated IL-17B mRNA expression. Altogether, these data indicate a Th17 dominated response upon oral immunization with F4 fimbriae and F4(+) ETEC infection. Our work also highlights that IL-17B and IL-17F participate in the immune response to protect the host against F4(+) ETEC infection and could aid in the design of future ETEC vaccines.

Prevalence of adhesin and toxin genes in E. coli strains isolated from diarrheic and non-diarrheic pigs from smallholder herds in northern and eastern Uganda.

PubMed

Ikwap, Kokas; Larsson, Jenny; Jacobson, Magdalena; Owiny, David Okello; Nasinyama, George William; Nabukenya, Immaculate; Mattsson, Sigbrit; Aspan, Anna; Erume, Joseph

2016-08-05

Enterotoxigenic E. coli (ETEC) significantly contribute to diarrhea in piglets and weaners. The smallholder pig producers in Uganda identified diarrhea as one of the major problems especially in piglets. The aim of this study was to; i) characterize the virulence factors of E. coli strains isolated from diarrheic and non-diarrheic suckling piglets and weaners from smallholder herds in northern and eastern Uganda and ii) identify and describe the post-mortem picture of ETEC infection in severely diarrheic piglets. Rectal swab samples were collected from 83 piglets and weaners in 20 herds and isolated E. coli were characterized by PCR, serotyping and hemolysis. The E. coli strains carried genes for the heat stable toxins STa, STb and EAST1 and adhesins F4 and AIDA-I. The genes for the heat labile toxin LT and adhesins F5, F6, F18 and F41 were not detected in any of the E. coli isolates. Where the serogroup could be identified, E. coli isolates from the same diarrheic pig belonged to the same serogroup. The prevalence of EAST1, STb, Stx2e, STa, AIDA-I, and F4 in the E. coli isolates from suckling piglets and weaners (diarrheic and non-diarrheic combined) was 29, 26.5, 2.4, 1.2, 16, and 8.4 %, respectively. However the prevalence of F4 and AIDA-I in E. coli from diarrheic suckling piglets alone was 22.2 and 20 %, respectively. There was no significant difference in the prevalence of the individual virulence factors in E. coli from the diarrheic and non-diarrheic pigs (p > 0.05). The main ETEC strains isolated from diarrheic and non-diarrheic pigs included F4/STb/EAST1 (7.2 %), F4/STb (1.2 %), AIDA/STb/EAST1 (8 %) and AIDA/STb (8 %). At post-mortem, two diarrheic suckling piglets carrying ETEC showed intact intestinal villi, enterocytes and brush border but with a layer of cells attached to the brush border, suggestive of ETEC infections. This study has shown that the F4 fimbriae is the most predominant in E. coli from diarrheic piglets in the study area and therefore an F4-based vaccine should be considered one of the preventive measures for controlling ETEC infections in the piglets in northern and eastern Uganda.

Dose-dependent effects of Lactobacillus rhamnosus on serum interleukin-17 production and intestinal T-cell responses in pigs challenged with Escherichia coli.

PubMed

Zhu, Yao-Hong; Li, Xiao-Qiong; Zhang, Wei; Zhou, Dong; Liu, Hao-Yu; Wang, Jiu-Feng

2014-03-01

The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 10(9) CFU/ml) or high (1 × 10(11) CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4(+) ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3(+) CD4(+) CD8(-) T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4(+) ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3(+) CD4(+) CD8(-) cells and Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells. The percentage of ileal intraepithelial CD3(+) CD4(-) CD8(+) cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4(+) ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4(+) ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3(+) CD4(+) CD8(-) T cells, the expansion of Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells, and the attenuation of F4(+) ETEC-induced increase in CD3(+) CD4(+) CD8(+) T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4(+) ETEC challenge, thus eliciting a strong proinflammatory response.

Dose-Dependent Effects of Lactobacillus rhamnosus on Serum Interleukin-17 Production and Intestinal T-Cell Responses in Pigs Challenged with Escherichia coli

PubMed Central

Zhu, Yao-Hong; Li, Xiao-Qiong; Zhang, Wei; Zhou, Dong; Liu, Hao-Yu

2014-01-01

The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 109 CFU/ml) or high (1 × 1011 CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4+ ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3+ CD4+ CD8− T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4+ ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3+ CD4+ CD8− cells and Peyer's patch CD3+ CD4− CD8− and CD3− CD4− CD8+ cells. The percentage of ileal intraepithelial CD3+ CD4− CD8+ cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4+ ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor β1 (TGF-β1), and ileal IL-10 was upregulated in the low-dose piglets after F4+ ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3+ CD4+ CD8− T cells, the expansion of Peyer's patch CD3+ CD4− CD8− and CD3− CD4− CD8+ cells, and the attenuation of F4+ ETEC-induced increase in CD3+ CD4+ CD8+ T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4+ ETEC challenge, thus eliciting a strong proinflammatory response. PMID:24389928

Complete Genome Sequence of Enterotoxigenic Escherichia coli Siphophage Seurat

PubMed Central

Doan, Dung P.; Lessor, Lauren E.; Hernandez, Adriana C.

2015-01-01

Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea in developing countries. Bacteriophage therapy has the potential to aid in the prevention and treatment of ETEC-related illness. To that end, we present here the complete genome of ETEC siphophage Seurat and describe its major features. PMID:25720682

Complete Genome Sequence of Enterotoxigenic Escherichia coli Siphophage Seurat.

PubMed

Doan, Dung P; Lessor, Lauren E; Hernandez, Adriana C; Kuty Everett, Gabriel F

2015-02-26

Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea in developing countries. Bacteriophage therapy has the potential to aid in the prevention and treatment of ETEC-related illness. To that end, we present here the complete genome of ETEC siphophage Seurat and describe its major features. Copyright © 2015 Doan et al.

Saccharomyces cerevisiae Modulates Immune Gene Expressions and Inhibits ETEC-Mediated ERK1/2 and p38 Signaling Pathways in Intestinal Epithelial Cells

PubMed Central

Zanello, Galliano; Berri, Mustapha; Dupont, Joëlle; Sizaret, Pierre-Yves; D'Inca, Romain

2011-01-01

Background Enterotoxigenic Escherichia coli (ETEC) infections result in large economic losses in the swine industry worldwide. ETEC infections cause pro-inflammatory responses in intestinal epithelial cells and subsequent diarrhea in pigs, leading to reduced growth rate and mortality. Administration of probiotics as feed additives displayed health benefits against intestinal infections. Saccharomyces cerevisiae (Sc) is non-commensal and non-pathogenic yeast used as probiotic in gastrointestinal diseases. However, the immuno-modulatory effects of Sc in differentiated porcine intestinal epithelial cells exposed to ETEC were not investigated. Methodology/Principal Findings We reported that the yeast Sc (strain CNCM I-3856) modulates transcript and protein expressions involved in inflammation, recruitment and activation of immune cells in differentiated porcine intestinal epithelial IPEC-1 cells. We demonstrated that viable Sc inhibits the ETEC-induced expression of pro-inflammatory transcripts (IL-6, IL-8, CCL20, CXCL2, CXCL10) and proteins (IL-6, IL-8). This inhibition was associated to a decrease of ERK1/2 and p38 MAPK phosphorylation, an agglutination of ETEC by Sc and an increase of the anti-inflammatory PPAR-γ nuclear receptor mRNA level. In addition, Sc up-regulates the mRNA levels of both IL-12p35 and CCL25. However, measurement of transepithelial electrical resistance displayed that Sc failed to maintain the barrier integrity in monolayer exposed to ETEC suggesting that Sc does not inhibit ETEC enterotoxin activity. Conclusions Sc (strain CNCM I-3856) displays multiple immuno-modulatory effects at the molecular level in IPEC-1 cells suggesting that Sc may influence intestinal inflammatory reaction. PMID:21483702

Association of vitamin D status with incidence of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli diarrhoea in children of urban Bangladesh.

PubMed

Ahmed, A M S; Soares Magalhaes, R J; Long, K Z; Ahmed, T; Alam, Md A; Hossain, Md I; Islam, Md M; Mahfuz, M; Mondal, D; Haque, R; Mamun, A A

2016-08-01

To evaluate the association between vitamin D status and diarrhoeal episodes by enterotoxigenic (ETEC), enteropathogenic (EPEC) and enteroaggregative (EAEC) E. coli in underweight and normal-weight children aged 6-24 months in urban Bangladesh. Cohorts of 446 normal-weight and 466 underweight children were tested separately for ETEC, EPEC and EAEC from diarrhoeal stool samples collected during 5 months of follow-up while considering vitamin D status at enrolment as the exposure. Cox proportional hazards models with unordered failure events of the same type were used to determine diarrhoeal risk factors after adjusting for sociodemographic and concurrent micronutrient status. Vitamin D status was not independently associated with the risk of incidence of ETEC, EPEC and EAEC diarrhoea in underweight children, but moderate-to-severe retinol deficiency was associated with reduced risk for EPEC diarrhoea upon adjustment. Among normal-weight children, insufficient vitamin D status and moderate-to-severe retinol deficiency were independently associated with 44% and 38% reduced risk of incidence of EAEC diarrhoea, respectively. These children were at higher risk of ETEC diarrhoea with vitamin D deficiency status when adjusted for micronutrient status only. This study demonstrates for the first time that normal-weight children with insufficient vitamin D status have a reduced risk of EAEC diarrhoea than children with sufficient status. Moderate-to-severe deficiency of serum retinol is associated with reduced risk of EPEC and EAEC diarrhoea in underweight and normal-weight children. © 2016 John Wiley & Sons Ltd.

Differential protection by cell wall components of Lactobacillus amylovorus DSM 16698Tagainst alterations of membrane barrier and NF-kB activation induced by enterotoxigenic F4+ Escherichia coli on intestinal cells.

PubMed

Roselli, Marianna; Finamore, Alberto; Hynönen, Ulla; Palva, Airi; Mengheri, Elena

2016-09-29

The role of Lactobacillus cell wall components in the protection against pathogen infection in the gut is still largely unexplored. We have previously shown that L. amylovorus DSM 16698 T is able to reduce the enterotoxigenic F4 + Escherichia coli (ETEC) adhesion and prevent the pathogen-induced membrane barrier disruption through the regulation of IL-10 and IL-8 expression in intestinal cells. We have also demonstrated that L. amylovorus DSM 16698 T protects host cells through the inhibition of NF-kB signaling. In the present study, we investigated the role of L. amylovorus DSM 16698 T cell wall components in the protection against F4 + ETEC infection using the intestinal Caco-2 cell line. Purified cell wall fragments (CWF) from L. amylovorus DSM 16698 T were used either as such (uncoated, U-CWF) or coated with S-layer proteins (S-CWF). Differentiated Caco-2/TC7 cells on Transwell filters were infected with F4 + ETEC, treated with S-CWF or U-CWF, co-treated with S-CWF or U-CWF and F4 + ETEC for 2.5 h, or pre-treated with S-CWF or U-CWF for 1 h before F4 + ETEC addition. Tight junction (TJ) and adherens junction (AJ) proteins were analyzed by immunofluorescence and Western blot. Membrane permeability was determined by phenol red passage. Phosphorylated p65-NF-kB was measured by Western blot. We showed that both the pre-treatment with S-CWF and the co- treatment of S-CWF with the pathogen protected the cells from F4 + ETEC induced TJ and AJ injury, increased membrane permeability and activation of NF-kB expression. Moreover, the U-CWF pre-treatment, but not the co-treatment with F4 + ETEC, inhibited membrane damage and prevented NF-kB activation. The results indicate that the various components of L. amylovorus DSM 16698 T cell wall may counteract the damage caused by F4 + ETEC through different mechanisms. S-layer proteins are essential for maintaining membrane barrier function and for mounting an anti-inflammatory response against F4 + ETEC infection. U-CWF are not able to defend the cells when they are infected with F4 + ETEC but may activate protective mechanisms before pathogen infection.

Oral rice-based vaccine induces passive and active immunity against enterotoxigenic E. coli-mediated diarrhea in pigs.

PubMed

Takeyama, Natsumi; Yuki, Yoshikazu; Tokuhara, Daisuke; Oroku, Kazuki; Mejima, Mio; Kurokawa, Shiho; Kuroda, Masaharu; Kodama, Toshiaki; Nagai, Shinya; Ueda, Susumu; Kiyono, Hiroshi

2015-09-22

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in both neonatal and weaned pigs. Because the cholera toxin B subunit (CTB) has a high level of amino acid identity to the ETEC heat-labile toxin (LT) B-subunit (LTB), we selected MucoRice-CTB as a vaccine candidate against ETEC-induced pig diarrhea. When pregnant sows were orally immunized with MucoRice-CTB, increased amounts of antigen-specific IgG and IgA were produced in their sera. CTB-specific IgG was secreted in the colostrum and transferred passively to the sera of suckling piglets. IgA antibodies in the colostrum and milk remained high with a booster dose after farrowing. Additionally, when weaned minipigs were orally immunized with MucoRice-CTB, production of CTB-specific intestinal SIgA, as well as systemic IgG and IgA, was induced. To evaluate the cross-protective effect of MucoRice-CTB against ETEC diarrhea, intestinal loop assay with ETEC was conducted. The fluid volume accumulated in the loops of minipigs immunized with MucoRice-CTB was significantly lower than that in control minipigs, indicating that MucoRice-CTB-induced cross-reactive immunity could protect weaned pigs from diarrhea caused by ETEC. MucoRice-CTB could be a candidate oral vaccine for inducing both passive and active immunity to protect both suckling and weaned piglets from ETEC diarrhea. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enzymatic Synthesis and Purification of Galactosylated Chitosan Oligosaccharides Reducing Adhesion of Enterotoxigenic Escherichia coli K88.

PubMed

Yan, Ya Lu; Hu, Ying; Simpson, David J; Gänzle, Michael G

2017-06-28

Enterotoxigenic Escherichia coli (ETEC) K88 causes diarrhea in weaned piglets and represent a suitable model system for ETEC causing childhood diarrhea. This study aimed to evaluate the effects of oligosaccharides against ETEC K88 adhesion to porcine erythrocytes with two bioassays. Galactosylated chitosan-oligosaccharides (Gal-COS) were synthesized through transgalactosylation by β-galactosidase. Fractions 2-5 of Gal-COS were obtained through cation exchange and size exclusion chromatography. Fractions 2-5 of acetylated Gal-COS were obtained through chemical acetylation followed by size exclusion chromatography. Gal-COS F2 containing the largest oligosaccharides had the highest antiadhesion activity with the minimum inhibitory concentration of 0.22 g/L, followed by F3 and F4. Acetylation of Gal-COS decreased their ability to reduce ETEC K88 adhesion. The composition of active oligosaccharides was determined with LC-MS. Galactosylation of COS produces oligosaccharides which reduce ETEC K88 adhesion; moreover, resulting oligosaccharides match the composition of human milk oligosaccharides, which prevent adhesion of multiple pathogens.

Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli

PubMed Central

Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

2015-01-01

Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue. PMID:26517723

Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli.

PubMed

Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

2015-01-01

Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue.

Porcine aminopeptidase N binds to F4+ enterotoxigenic Escherichia coli fimbriae.

PubMed

Xia, Pengpeng; Wang, Yiting; Zhu, Congrui; Zou, Yajie; Yang, Ying; Liu, Wei; Hardwidge, Philip R; Zhu, Guoqiang

2016-02-09

F4(+) enterotoxigenic Escherichia coli (ETEC) strains cause diarrheal disease in neonatal and post-weaned piglets. Several different host receptors for F4 fimbriae have been described, with porcine aminopeptidase N (APN) reported most recently. The FaeG subunit is essential for the binding of the three F4 variants to host cells. Here we show in both yeast two-hybrid and pulldown assays that APN binds directly to FaeG, the major subunit of F4 fimbriae, from three serotypes of F4(+) ETEC. Modulating APN gene expression in IPEC-J2 cells affected ETEC adherence. Antibodies raised against APN or F4 fimbriae both reduced ETEC adherence. Thus, APN mediates the attachment of F4(+) E. coli to intestinal epithelial cells.

Cloning, expression, purification, crystallization and X-ray crystallographic analysis of CofB, the minor pilin subunit of CFA/III from human enterotoxigenic Escherichia coli.

PubMed

Kawahara, Kazuki; Oki, Hiroya; Fukakusa, Shunsuke; Maruno, Takahiro; Kobayashi, Yuji; Motooka, Daisuke; Taniguchi, Tooru; Honda, Takeshi; Iida, Tetsuya; Nakamura, Shota; Ohkubo, Tadayasu

2015-06-01

Colonization factor antigen III (CFA/III) is one of the virulence factors of human enterotoxigenic Escherichia coli (ETEC) that forms the long, thin, proteinaceous fibres of type IV pili through assembly of its major and minor subunits CofA and CofB, respectively. The crystal structure of CofA has recently been reported; however, the lack of structural information for CofB, the largest among the known type IV pilin subunits, hampers a comprehensive understanding of CFA/III pili. In this study, constructs of wild-type CofB with an N-terminal truncation and the corresponding SeMet derivative were cloned, expressed, purified and crystallized. The crystals belonged to the rhombohedral space group R32, with unit-cell parameters a = b = 103.97, c = 364.57 Å for the wild-type construct and a = b = 103.47, c = 362.08 Å for the SeMet-derivatized form. Although the diffraction quality of these crystals was initially very poor, dehydration of the crystals substantially improved the resolution limit from ∼ 4.0 to ∼ 2.0 Å. The initial phase was solved by the single-wavelength anomalous dispersion (SAD) method using a dehydrated SeMet CofB crystal, which resulted in an interpretable electron-density map.

Controlled study on enteropathogens in travellers returning from the tropics with and without diarrhoea.

PubMed

Paschke, C; Apelt, N; Fleischmann, E; Perona, P; Walentiny, C; Löscher, T; Herbinger, K-H

2011-08-01

Diarrhoea is the most frequent health problem among travellers in the tropics. However, data on the spectrum and relevance of enteropathogens in international travellers with and without diarrhoea are limited. Stool samples from 114 cases of diarrhoea in travellers returning from the tropics were collected for microbiological examination and PCR for norovirus genogroups I and II, enteroaggregative Escherichia coli (EAEC), and enterotoxigenic E. coli (ETEC) producing heat-labile toxin (LT) and heat-stable toxin (ST). Travel and laboratory data of cases were compared with those of 56 travellers without diarrhoea. Among cases, EAEC was found in 45% of stool samples, followed by LT-ETEC (20%), ST-ETEC (16%), Blastocystis hominis (15%), Campylobacter jejuni (12%), norovirus (11%), Giardia lamblia (6%), Shigella spp. (6%), and Salmonella spp., Cryptosporidium spp., and Cyclospora cayetanensis (3% each). However, only for EAEC, ST-ETEC, Blastocystis and Campylobacter was the prevalence significantly higher among cases than among controls. Co-infections were common: 61% for cases and 13% for controls. The most common travel destination was Asia (54%), followed by Africa (35%) and Latin America (9%). The highest relative risk for diarrhoea was calculated for travellers to West Africa, East Africa, and South Asia. In this study, EAEC, LT-ETEC and ST-ETEC were detected most frequently in cases of travellers' diarrhoea. Although enteric infections with EAEC, ST-ETEC and Campylobacter often cause diarrhoea, the pathogenetic relevance remains unclear for most of the other enteropathogens, because of significant prevalence rates also being seen in controls without diarrhoea and the high frequency of co-infections. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

Resistance to drugs and heavy metals, colicin production, and biochemical characteristics of selected bovine and porcine Escherichia coli strains.

PubMed Central

Harnett, N M; Gyles, C L

1984-01-01

A study was made of resistance to heavy metals and antibiotics, biochemical characteristics, and colicinogeny in selected strains of Escherichia coli of O serogroups 8, 9, 20, 64, 101, and X46. Of 42 strains that were investigated, 26 were porcine enterotoxigenic E. coli (ETEC), 8 were porcine non-enterotoxigenic E. coli (NETEC), and 8 were bovine ETEC. Multiple resistance to antimicrobial agents was common among the strains, and resistance to chloramphenicol and kanamycin was less common than resistance to other drugs, possibly reflecting the lower frequency of use of these agents in pigs and calves. Colicin production was a more common property of porcine ETEC (80.8%) than of porcine NETEC (25%), and all porcine ETEC of O serogroups 101 and 64 were colicinogenic. Equal numbers of bovine ETEC strains were colicinogenic as were non-colicinogenic. Resistance of bovine and porcine strains to sodium arsenate, mercury, and tellerium was 90, 16, and 5%, respectively. There was a close relationship between serogroup and biochemical reactions among the E. coli strains tested. PMID:6391383

A tripartite fusion, FaeG-FedF-LT(192)A2:B, of enterotoxigenic Escherichia coli (ETEC) elicits antibodies that neutralize cholera toxin, inhibit adherence of K88 (F4) and F18 fimbriae, and protect pigs against K88ac/heat-labile toxin infection.

PubMed

Ruan, Xiaosai; Liu, Mei; Casey, Thomas A; Zhang, Weiping

2011-10-01

Enterotoxigenic Escherichia coli (ETEC) strains expressing K88 (F4) or F18 fimbriae and heat-labile (LT) and/or heat-stable (ST) toxins are the major cause of diarrhea in young pigs. Effective vaccines inducing antiadhesin (anti-K88 and anti-F18) and antitoxin (anti-LT and anti-ST) immunity would provide broad protection to young pigs against ETEC. In this study, we genetically fused nucleotides coding for peptides from K88ac major subunit FaeG, F18 minor subunit FedF, and LT toxoid (LT(192)) A2 and B subunits for a tripartite adhesin-adhesin-toxoid fusion (FaeG-FedF-LT(192)A2:B). This fusion was used for immunizations in mice and pigs to assess the induction of antiadhesin and antitoxin antibodies. In addition, protection by the elicited antiadhesin and antitoxin antibodies against a porcine ETEC strain was evaluated in a gnotobiotic piglet challenge model. The data showed that this FaeG-FedF-LT(192)A2:B fusion elicited anti-K88, anti-F18, and anti-LT antibodies in immunized mice and pigs. In addition, the anti-porcine antibodies elicited neutralized cholera toxin and inhibited adherence against both K88 and F18 fimbriae. Moreover, immunized piglets were protected when challenged with ETEC strain 30302 (K88ac/LT/STb) and did not develop clinical disease. In contrast, all control nonvaccinated piglets developed severe diarrhea and dehydration after being challenged with the same ETEC strain. This study clearly demonstrated that this FaeG-FedF-LT(192)A2:B fusion antigen elicited antibodies that neutralized LT toxin and inhibited the adherence of K88 and F18 fimbrial E. coli strains and that this fusion could serve as an antigen for vaccines against porcine ETEC diarrhea. In addition, the adhesin-toxoid fusion approach used in this study may provide important information for developing effective vaccines against human ETEC diarrhea.

Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR- pigs challenged with an F4+ ETEC/VTEC/EPEC strain.

PubMed

Zhou, Dong; Zhu, Yao-Hong; Zhang, Wei; Wang, Meng-Ling; Fan, Wen-Yi; Song, Dan; Yang, Gui-Yan; Jensen, Bent Borg; Wang, Jiu-Feng

2015-09-17

Although breeding of F4 receptor - negative (F4R(-)) pigs may prevent post-weaning diarrhea, the underlying immunity is poorly understood. Here, various doses of a Bacillus licheniformis and Bacillus subtilis mixture (BLS-mix) were orally administered to F4ab/acR(-) pigs for 1 week before F4 (K88) - positive ETEC/VTEC/EPEC challenge. Administration of BLS-mix increased the percentage of Foxp3(-)IL-10(+) T cells but not of Foxp3(+)IL-10(+) regulatory T (Treg) cells among peripheral blood CD4(+) T cells. A low dose of BLS-mix feeding resulted in increased the expression of IL-6, TNF-α, IL-10, and the transcription factors Foxp3 and T-bet mRNAs in the jejunum. Administration of either a low or high dose BLS-mix also led to an increase in the percentage of CD4(+)Foxp3(+) Treg cells among intraepithelial lymphocytes and CD4(+)IL-10(+) T cells in the small intestinal Peyer's patches and the lamina propria of F4ab/acR(-) pigs following F4(+) ETEC/VTEC/EPEC challenge. The increased number of IL-10-producing CD4(+) T cells was attributed to an increase in the proportion of Foxp3(-)IL-10(+) Treg cells rather than Foxp3(+)IL-10(+) Treg cells. Our data indicate that oral administration of BLS-mix to newly weaned F4ab/acR(-) pigs ameliorates enteritis in an F4(+) ETEC/VTEC/EPEC model; however, induction of IL-10-producing Foxp3(-) Treg cells by BLS-mix administration cannot account for the protection of newly weaned F4ab/acR(-) pigs from F4(+) ETEC/VTEC/EPEC infection, and that excessive generation of CD4(+)IL-10(+) T cells following consumption of BLS-mix during episodes of intestinal inflammation that is caused by enteric pathogens might prohibit clearance of the pathogen. Select probiotic mixtures may allow for tailoring strategies to prevent infectious diseases.

Frequency of indicator bacteria, Salmonella and diarrhoeagenic Escherichia coli pathotypes on ready-to-eat cooked vegetable salads from Mexican restaurants.

PubMed

Bautista-De León, H; Gómez-Aldapa, C A; Rangel-Vargas, E; Vázquez-Barrios, E; Castro-Rosas, J

2013-06-01

The presence of coliform bacteria, faecal coliforms, Escherichia coli, diarrhoeagenic E. coli pathotypes (DEP) and Salmonella were determined in ready-to-eat cooked vegetable salads (RECS) from restaurants in Pachuca city, Mexico. The RECS were purchased from three types of restaurants: national chain restaurants (A), local restaurants (B) and small restaurants (C). Two restaurants for each A and B, and three for C, were included. Forty RECS samples were purchased at each A and B restaurant and 20 at each C restaurant. Of the overall total of 220 analysed samples, 100, 98·2, 72·3, 4·1 and 4·1% had coliform bacteria, faecal coliforms, E. coli, DEP and Salmonella, respectively. Identified DEP included enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC) and Shiga toxin-producing E. coli (STEC). The EPEC, ETEC and STEC were isolated each from 1·4% of samples. No E. coli O157:H7 were detected in any STEC-positive samples. The analysis of Kruskal-Wallis anova and median test of microbiological data showed that the microbiological quality of RECS did not differ between the different restaurants (P > 0·05). This is the first report regarding microbiological quality and Salmonella, enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC) and Shiga toxin-producing E. coli (STEC) isolation from ready-to-eat cooked vegetable salads from Mexican restaurants. Ready-to-eat cooked vegetable salads could be an important factor contributing to the endemicity of EPEC, ETEC and STEC, and Salmonella caused gastroenteritis in Mexico. © 2013 The Society for Applied Microbiology.

Pilot study of whole-blood gamma interferon response to the Vibrio cholerae toxin B subunit and resistance to enterotoxigenic Escherichia coli-associated diarrhea.

PubMed

Flores, Jose; DuPont, Herbert L; Paredes-Paredes, Mercedes; Aguirre-Garcia, M Magdalena; Rojas, Araceli; Gonzalez, Alexei; Okhuysen, Pablo C

2010-05-01

Enterotoxigenic Escherichia coli (ETEC), which produces heat-labile toxin (LT), is a common cause of travelers' diarrhea (TD). The B subunit of ETEC LT is immunologically related to the B subunit of Vibrio cholerae toxin (CT). In this pilot study we evaluated the whole-blood gamma interferon response to CT B in 17 U.S. adults traveling to Mexico. Only one of nine subjects who demonstrated a cellular immune response as determined by whole-blood gamma interferon production to CT B on arrival to Mexico developed diarrhea, whereas five of eight without a cellular response developed diarrhea. Markers of the cellular immune response to ETEC LT could help in identifying individuals immune to ETEC LT, and these markers deserve additional study.

Identification and quantification of virulence factors of enterotoxigenic Escherichia coli by high-resolution melting curve quantitative PCR.

PubMed

Wang, Weilan; Zijlstra, Ruurd T; Gänzle, Michael G

2017-05-15

Diagnosis of enterotoxigenic E. coli (ETEC) associated diarrhea is complicated by the diversity of E.coli virulence factors. This study developed a multiplex quantitative PCR assay based on high-resolution melting curves analysis (HRM-qPCR) to identify and quantify genes encoding five ETEC fimbriae related to diarrhea in swine, i.e. K99, F41, F18, F6 and K88. Five fimbriae expressed by ETEC were amplified in multiple HRM-qPCR reactions to allow simultaneous identification and quantification of five target genes. The assay was calibrated to allow quantification of the most abundant target gene, and validated by analysis of 30 samples obtained from piglets with diarrhea and healthy controls, and comparison to standard qPCR detection. The five amplicons with melting temperatures (Tm) ranging from 74.7 ± 0.06 to 80.5 ± 0.15 °C were well-separated by HRM-qPCR. The area of amplicons under the melting peak correlated linearly to the proportion of the template in the calibration mixture if the proportion exceeded 4.8% (K88) or <1% (all other amplicons). The suitability of the method was evaluated using 30 samples from weaned pigs aged 6-7 weeks; 14 of these animals suffered from diarrhea in consequence of poor sanitary conditions. Genes encoding fimbriae and enterotoxins were quantified by HRM-qPCR and/or qPCR. The multiplex HRM-qPCR allowed accurate analysis when the total gene copy number of targets was more than 1 × 10 5 / g wet feces and the HRM curves were able to simultaneously distinguish fimbriae genes in the fecal samples. The relative quantification of the most abundant F18 based on melting peak area was highly correlated (P < 0.001; r 2  = 0.956) with that of individual qPCR result but the correlation for less abundant fimbriae was much lower. The multiplex HRM assay identifies ETEC virulence factors specifically and efficiently. It correctly indicated the predominant fimbriae type and additionally provides information of presence/ absence of other fimbriae types and it could find broad applications for pathogen diagnosis.

Antibacterial and Antidiarrheal Activities of Plant Products against Enterotoxinogenic Escherichia coli

PubMed Central

Dubreuil, J. Daniel

2013-01-01

Enterotoxigenic Escherichia coli (ETEC) produces two types of enterotoxins: heat-labile (LT) and heat-stable (STa and STb). These molecules are involved in the induction of secretory diarrhea in animals including humans. This condition is currently treated using a fluid replacement therapy and antibiotics. This treatment is often not available to people in developing countries, and several die from the condition provoke by ETEC. Over the years, plants and plant extracts have been use as traditional medicine to treat various gastrointestinal ailments including diarrhea. Many of these plant products have been claimed to be active against diarrhea, however few have been extensively studied. The main objective of this review was to gather the scattered information on the antidiarrheal activities reported for various plant products on ETEC. This includes two major effects: (1) The inhibitory effect on bacterial growth or viability and (2) The interference with ETEC enterotoxins activity upon the intestinal epithelium. We will focus on plant products and extracts for which we have major indications of their biological activity against ETEC and their enterotoxins. Because Vibrio cholerae toxin (CT) is structurally, antigenically and mechanistically related to LT, it will also be discussed in this review. PMID:24212181

Traveler's diarrhea at sea: three outbreaks of waterborne enterotoxigenic Escherichia coli on cruise ships.

PubMed

Daniels, N A; Neimann, J; Karpati, A; Parashar, U D; Greene, K D; Wells, J G; Srivastava, A; Tauxe, R V; Mintz, E D; Quick, R

2000-04-01

Enterotoxigenic Escherichia coli (ETEC) has become the leading bacterial cause of gastroenteritis outbreaks on cruise ships. Investigation of recent outbreaks of ETEC gastroenteritis on 3 cruise ships indicated that all were associated with consuming beverages with ice cubes on board the ship (relative risk [RR], 1.4, 95% confidence interval [CI], 1.0-1.9, P=.02; RR, 1.9, 95% CI, 1.3-2. 9, P<.001; and RR, 1.3, 95% CI, 1.0-1.6, P<.01), and 2 were associated with drinking unbottled water (RR, 2.7, 95% CI, 1.8-4.1, P<.001; RR, 1.7, 95% CI, 1.3-2.3, P<.001). Multiple ETEC serotypes were detected in patients' stool specimens in each of the 3 outbreaks, and 12 (38%) of 32 isolates were resistant to > or =3 antimicrobial agents. ETEC appears to be emerging as a waterborne pathogen on cruise ships. Water bunkered in overseas ports was the likely source of ETEC infection in these outbreaks. To ensure passenger safety, cruise ships that take on water in foreign ports must ensure that water treatment and monitoring systems function properly.

Presence of non-O157 Shiga toxin-producing Escherichia coli, enterotoxigenic E. coli, enteropathogenic E. coli and Salmonella in fresh beetroot (Beta vulgaris L.) juice from public markets in Mexico.

PubMed

Gómez-Aldapa, Carlos A; Rangel-Vargas, Esmeralda; Bautista-De León, Haydee; Castro-Rosas, Javier

2014-10-01

Unpasteurized juice has been associated with foodborne illness outbreaks for many years. Beetroot is a vegetable grown all over the world in temperate areas. In Mexico beetroot is consumed cooked in salads or raw as fresh unpasteurized juices. No data about the microbiological quality or safety of unpasteurized beetroot juices are available. Indicator bacteria, diarrheagenic Escherichia coli pathotypes (DEP) and Salmonella frequencies were determined for fresh unpasteurized beetroot juice from restaurants. One hundred unpasteurized beetroot juice samples were collected from public markets in Pachuca, Mexico. Frequencies in these samples were 100%, 75%, 53%, 9% and 4% of positive samples, for coliform bacteria, fecal coliforms, E. coli, DEP and Salmonella, respectively. Identified DEP included enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC) and non-O157 Shiga toxin-producing E. coli (STEC). Identified Salmonella serotypes included Typhimurium and Enteritidis. This is the first report of microbiological quality and atypical EPEC, ETEC, non-O157 STEC and Salmonella isolation from fresh raw beetroot juice in Mexico. Fresh raw beetroot juice from markets is very probably an important factor contributing to the endemicity of atypical EPEC, ETEC, non-O157 STEC and Salmonella-related gastroenteritis in Mexico. © 2014 Society of Chemical Industry.

Lactobacillus plantarum Enhanced IL-22 Production in Natural Killer (NK) Cells That Protect the Integrity of Intestinal Epithelial Cell Barrier Damaged by Enterotoxigenic Escherichia coli.

PubMed

Qiu, Yueqin; Jiang, Zongyong; Hu, Shenglan; Wang, Li; Ma, Xianyong; Yang, Xuefen

2017-11-13

Interleukin (IL)-22-producing Natural Killer (NK) cells protect the gut epithelial cell barrier from pathogens. A strain of probiotics, Lactobacillus plantarum (L. plantarum, LP), was previously found by our laboratory to significantly improve the mucosal barrier integrity and function of the small intestine in pigs. However, it was unclear whether LP benefited the intestinal mucosal barrier via interactions with the intestinal NK cells. The present study, therefore, was focused on the therapeutic effect of NK cells that were stimulated by LP on attenuating enterotoxigenic Escherichia coli (ETEC)-induced the damage to the integrity of the epithelial cell barrier. The results showed that LP can efficiently increase protein levels of the natural cytotoxicity receptor (NCR) family, and the expression levels of IL-22 mRNA and protein in NK cells. Transfer of NK cells stimulated by LP conferred protection against ETEC K88-induced intestinal epithelial barrier damage in NCM460 cells. We found that NK cells stimulated by LP could partially offset the reduction in NCM460 cell monolayers transepithelial electrical resistance (TEER) caused by ETEC K88, and increase ZO-1 and occludin mRNA and protein expressions by ETEC K88-infected NCM460 cells. Furthermore, adding NK cells that were stimulated by LP to ETEC K88-infected NCM460cells, IL-22R1, p-Stat3, and p-Tyk2 expression by NCM460 cells was increased. Mechanistic experiment showed that NK cells stimulated by LP lost the function of maintaining TEER of NCM460 cells challenged with ETEC K88, when polyclonal anti-IL-22 antibody was used to block IL-22 production. Collectively, our results suggested that LP stimulation of NK could enhance IL-22 production, which might be able to provide defense against ETEC-induced damage to the integrity of intestinal epithelial barrier.

Differentiation of F4 receptor profiles in pigs based on their mucin 4 polymorphism, responsiveness to oral F4 immunization and in vitro binding of F4 to villi.

PubMed

Nguyen, V U; Goetstouwers, T; Coddens, A; Van Poucke, M; Peelman, L; Deforce, D; Melkebeek, V; Cox, E

2013-03-15

F4(+) enterotoxigenic Escherichia coli (F4(+) ETEC) are an important cause of diarrhoea and mortality in piglets. F4(+) ETEC use their F4 fimbriae to adhere to specific receptors (F4Rs) on small intestinal brush borders, resulting in colonization of the small intestine. To prevent pigs from post-weaning diarrhoea, pigs should be vaccinated during the suckling period. Previously, we demonstrated that F4acR(+), but not F4acR(-) piglets could be orally immunized with purified F4 fimbriae resulting in a protective immunity against F4(+) ETEC infections, indicating that this immune response was F4R dependent. Recently, aminopeptidase N has been identified as a glycoprotein receptor important for this oral immune response. However, in some oral immunization experiments, a few F4acR(+) piglets did not show an antibody response upon oral immunization, suggesting additional receptors. Therefore, the binding profile of F4 to brush border membrane (glyco)proteins was determined for pigs differing in F4-specific antibody response upon oral immunization, in in vitro adhesion of F4(+)E. coli to small intestinal villi, and in Muc4 genotype. Six groups of pigs could be identified. Only two groups positive in all three assays showed two high molecular weight (MW) glycoprotein bands (>250kDa) suggesting that these high MW bands are linked to the MUC4 susceptible genotype. The fact that these bands were absent in the MUC4 resistant group which showed a positive immune response against F4 and was positive in the adhesion test confirm that at least one or perhaps more other F4Rs exist. Interestingly, two pigs that were positive in the villous adhesion assay did not show an immune response against F4 fimbriae. This suggests that a third receptor category might exist which allows the bacteria to adhere but does not allow effective immunization with soluble F4 fimbriae. Future research will be necessary to confirm or reveal the identity of these receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Streptococcus faecium M 74 in control of diarrhoea induced by a human enterotoxigenic Escherichia coli strain in an infant rabbit model.

PubMed

Wadström, T

1984-08-01

Streptococcus faecium strain M 74 was evaluated as a prophylacticum for enterotoxigenic Escherichia coli (ETEC) diarrhoea with human isolates of E. coli with CFA/I and CFA/II surface fimbrial haemagglutinins (adhesins) in a rabbit model. Young rabbits (3 to 4 days old) were given S. faecium organisms (5 X 10(9)) 15 min before (group A), 6 h before (group B) and 12 h after (group C) challenge with ETEC organisms. Only 4 out of 26 rabbits in group A, 6 out of 21 in group B and 7 out of 23 in group C developed diarrhoea. In conclusion, this S. faecium strain M 74 seems efficiently to protect animals from ETEC diarrhoea when given as a prophylactic agent at a high dose. This animal model seems useful for comparative studies on new preventive methods for ETEC diarrhoea such as testing probiotics and antiadhesive drugs.

Maillard neoglycans as inhibitors for in vitro adhesion of F4+ enterotoxigenic Escherichia coli to piglet intestinal cells.

PubMed

Sarabia-Sainz, Héctor Manuel; Mata Haro, Verónica; Sarabia Sainz, José Andre-I; Vázquez-Moreno, Luz; Montfort, Gabriela Ramos-Clamont

2017-01-01

Adhesion of enterotoxigenic (ETEC) E. coli to host intestinal cells is mediated by lectin-like fimbriae that bind to specific glycan moieties on the surfaces of enterocytes. To prevent in vitro binding of E. coli F4 fimbriae (F4 ETEC + ) to piglet enterocytes, neoglycans were synthesized by the Maillard reaction conjugating lactose (Lac), galacto-oligosaccharides (GOS) or chitin oligosaccharides (Ochit) to porcine serum albumin (PSA). Neoglycans were characterized by SDS-PAGE, intrinsic tryptophan fluorescence and recognition by plant lectins, as well as by F4 ETEC variants. Electrophoretic patterns suggested the binding to PSA of 63, 13 and 2 molecules of Lac, GOS and Ochit, respectively. All neoglycans displayed quenching of tryptophan fluorescence consistent with the degree of glycation estimated by SDS-PAGE. Plant lectins recognized the neoglycans according to their specificity, whereas antigenic variants of F4 ETEC (ab, ac and ad) recognized PSA-Ochit and PSA-Lac with higher affinity than that for GOS. Neoglycans partially hindered the in vitro binding of F4 + ETEC to piglet enterocytes in a dose-dependent manner. The most effective blocking was observed with PSA-Lac that partially inhibited the adhesion of bacteria to enterocytes in a dose dependent manner, as quantified by flow cytometry. Increased production of the cytokines IL-6 and TNF-α was observed in response to F4 + ETEC infection of enterocytes and production was reduced in the presence of PSA-Ochit and PSA-GOS. These results suggest that neoglycans synthesized by the Maillard reaction could be useful in the prophylaxis of diarrhea in piglets.

Outbreak of CTX-M-15-Producing Enterotoxigenic Escherichia coli O159:H20 in the Republic of Korea in 2016.

PubMed

Kim, Jin Seok; Park, Jungsun; Shin, Eunkyung; Kim, Soojin; Oh, Sung Suck; Yang, Hyo-Jin; Kim, Dae-Won; Oh, Kyung-Hwan; Kim, Yonghoon; Kim, Min; Kwon, Mun Ju; Na, Kyoungin; Lee, Jin; Cho, En-Hi; Kang, Byung-Hak; Kwak, Hyo-Sun; Seong, Won Keun; Kim, Junyoung

2017-09-01

We investigated an outbreak of enterotoxigenic Escherichia coli (ETEC) O159:H20 associated with the consumption of a tossed-noodle dish in a high school in 2016. Thirty-three ETEC strains isolated from clinical and food samples were genetically indistinguishable. The outbreak strains were resistant to third-generation cephalosporins and harbored a bla CTX-M-15 gene on a 97-kb self-transferable IncK plasmid. This is the first outbreak caused by CTX-M-15-producing ETEC strains. Copyright © 2017 American Society for Microbiology.

A foodborne outbreak of gastrointestinal illness caused by enterotoxigenic Escherichia coli serotype O169:H41 in Osaka, Japan.

PubMed

Harada, Tetsuya; Itoh, Kaoru; Yamaguchi, Yuko; Hirai, Yuji; Kanki, Masashi; Kawatsu, Kentaro; Seto, Kazuko; Taguchi, Masumi; Kumeda, Yuko

2013-01-01

We describe our laboratory investigation of a massive foodborne outbreak of gastrointestinal illness caused by enterotoxigenic Escherichia coli (ETEC) serotype O169:H41 that occurred during a 2-day traditional festival held in September 2012 in Osaka Prefecture, Japan. Of 126 customers who patronized a particular Japanese restaurant during the event, 102 developed symptoms of gastrointestinal disease. We isolated strains of ETEC serotype O169:H41 from 1 food sample and from fecal samples collected from 19 of 34 patients and 2 of 4 food handlers. Pulsed-field gel electrophoresis analysis of these isolates suggested that the foodborne pathogen that caused the diarrheal outbreak was a specific clone of ETEC serotype O169:H41. Based on these findings and our interviews with the restaurant owner and employees, we concluded that a likely cause of the outbreak was an overwhelmed capacity of the restaurant kitchen in terms of preservation of sanitary procedures during the festival and the inability of the restaurant staff to handle the relatively large quantity of food to ensure a lack of contamination with ETEC. Thus, we reconfirm that ETEC strains of serotype O169:H41 remain important causes of domestic foodborne outbreaks in developed countries, including Japan.

In vivo therapeutic efficacy and pharmacokinetics of colistin sulfate in an experimental model of enterotoxigenic Escherichia coli infection in weaned pigs.

PubMed

Rhouma, Mohamed; Beaudry, Francis; Thériault, William; Bergeron, Nadia; Beauchamp, Guy; Laurent-Lewandowski, Sylvette; Fairbrother, John Morris; Letellier, Ann

2016-05-27

Enterotoxigenic Escherichia coli (ETEC: F4) associated with post-weaning diarrhea (PWD) in pigs has developed resistance against several antimicrobial families, leading to increased use of colistin sulfate (CS) for the treatment of this disease. The objective of this study was to determine the efficacy of oral CS treatment in experimental PWD due to ETEC: F4 challenge and determine the effect of this challenge on CS intestinal absorption. In this study, 96 pigs were divided into two trials based on CS dose (100 000 or 50 000 IU/kg). Fecal shedding of ETEC: F4, total E. coli, and CS-resistant E. coli, diarrhea scores, and weight changes were evaluated. Colistin sulfate plasma concentrations were determined by HPLC-MS/MS. Regardless of the dose, CS treatment resulted in a reduction of fecal ETEC: F4 and total E. coli shedding, and in diarrhea scores but only during the treatment period. However, CS treatment resulted in a slight increase in fecal shedding of CS resistant E. coli and did not prevent weight loss in challenged pigs. In addition, challenge with ETEC: F4 resulted in an increase of CS intestinal absorption. Our study is among the first to demonstrate that under controlled conditions, CS was effective in reducing fecal shedding of ETEC: F4 and total E. coli in experimental PWD. However, CS treatment was associated with a slight selection pressure on E. coli and did not prevent pig weight loss. Further studies are needed in field conditions, to better characterize CS therapeutic regimen efficacy and bacterial resistance dissemination.

Production of specific IgY antibody to the recombinant FanC protein produced in Escherichia coli.

PubMed

Nasiri, Khadijeh; Zibaee, Saeed; Nassiri, Mohammadreza; Tahmoorespur, Mojtaba; Haghparast, Alireza

2016-08-01

Enterotoxigenic Escherichia coli (ETEC) strains are one of the primary causes of diarrhea in newborn calves and in humans, pigs, and sheep. IgY technology has been identified as a promising alternative to generating a mass amount of specific antibody for use in immunotherapy and immunodiagnostics. The purpose of this study was to produce specific antibody by egg yolk antibody (IgY) to recombinant FanC protein from ETEC. FanC (K99) gene was amplified from ETEC by specific primers and polymerase chain reaction. The gene was cloned and subcloned into pTZ57R/T and pET32a (+) vectors, respectively. Recombinant vector was transferred into E. coli BL21 CodonPlus (DE3). Protein expression was investigated by 1 mM IPTG induction. Hens were immunized by the purified recombinant FanC protein. The activity and specificity of the IgY antibody were detected by dot-blotting, Western blotting, and indirect ELISA. We obtained FanC specific IgYs by immunizing the hens with the recombinant FanC protein. The anti-FanC IgY showed binding specifically to the FanC protein of ETEC. The results emphasize that specific IgY against the recombinant FanC protein could be recommended as a candidate for passive immunization against ETEC infection in animals and humans.

Production of specific IgY antibody to the recombinant FanC protein produced in Escherichia coli

PubMed Central

Nasiri, Khadijeh; Zibaee, Saeed; Nassiri, Mohammadreza; Tahmoorespur, Mojtaba; Haghparast, Alireza

2016-01-01

Objective(s): Enterotoxigenic Escherichia coli (ETEC) strains are one of the primary causes of diarrhea in newborn calves and in humans, pigs, and sheep. IgY technology has been identified as a promising alternative to generating a mass amount of specific antibody for use in immunotherapy and immunodiagnostics. The purpose of this study was to produce specific antibody by egg yolk antibody (IgY) to recombinant FanC protein from ETEC. Materials and Methods: FanC (K99) gene was amplified from ETEC by specific primers and polymerase chain reaction. The gene was cloned and subcloned into pTZ57R/T and pET32a (+) vectors, respectively. Recombinant vector was transferred into E. coli BL21 CodonPlus (DE3). Protein expression was investigated by 1 mM IPTG induction. Hens were immunized by the purified recombinant FanC protein. The activity and specificity of the IgY antibody were detected by dot-blotting, Western blotting, and indirect ELISA. Results: We obtained FanC specific IgYs by immunizing the hens with the recombinant FanC protein. The anti-FanC IgY showed binding specifically to the FanC protein of ETEC. Conclusion: The results emphasize that specific IgY against the recombinant FanC protein could be recommended as a candidate for passive immunization against ETEC infection in animals and humans. PMID:27746871

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines for Shigella, Salmonella, enterotoxigenic E. coli (ETEC) enterohemorragic E. coli (EHEC) and Campylobacter jejuni

PubMed Central

O’Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Carlos Salazar, Juan; Montero, David

2015-01-01

In Part II we discuss the following bacterial pathogens: Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic) and Campylobacter jejuni. In contrast to the enteric viruses and Vibrio cholerae discussed in Part I of this series, for the bacterial pathogens described here there is only one licensed vaccine, developed primarily for Vibrio cholerae and which provides moderate protection against enterotoxigenic E. coli (ETEC) (Dukoral®), as well as a few additional candidates in advanced stages of development for ETEC and one candidate for Shigella spp. Numerous vaccine candidates in earlier stages of development are discussed. PMID:25715096

The Role of Educational Technology Professionals as Perceived by Building Administrators

ERIC Educational Resources Information Center

Murphy, Cheryl A.; Allred, Jonathan B.; Brescia, William F.

2018-01-01

Educational Technology (ETEC) professionals in the United States (US) fill multiple roles in public school systems. While these roles can be classified into broad categories, what remains unclear are the expectations and priorities for the completion of these roles and the tasks associated within each role category. In order for ETEC professionals…

Electrochemical magneto immunosensor based on endogenous β-galactosidase enzyme to determine enterotoxicogenic Escherichia coli F4 (K88) in swine feces using square wave voltammetry.

PubMed

Viviana Tarditto, Lorena; Alicia Zon, María; García Ovando, Hugo; Roberto Vettorazzi, Nelio; Javier Arévalo, Fernando; Fernández, Héctor

2017-11-01

Diseases caused by enterotoxicogenic Escherichia coli F4 (K88) (ETEC F4) are a problem in swine production establishments. Due to the high rate of mortality and morbidity of E. coli infections, a rapid and accurate diagnosis is important in order to choose an appropriate treatment to reduce the economic impact. Therefore, an electrochemical magneto-immunosensor (EMI) was developed to detect and quantify ETEC F4 in swine feces samples through a direct non-competitive immunoassay. ETEC F4 was selectively captured by immunomagnetic separation. The detection principle was based on the activity of β-galactosidase endogenous enzyme (β-gal), which hydrolyses the p-aminophenyl-β-D-galactopyranoside (p-APG) producing p-aminophenol (p-AP), which was oxidized on a carbon screen printed electrode (CSPE) using square wave voltammetry (SWV). All parameters related to construction and electrochemical responses were optimized. The total analysis time to quantify ETEC F4 using the EMI was less than 2h and the limit of detection (LOD) was 33CFUmL -1 . The perceptual relative error (%E r ) was 20%. The magneto-immunosensor was validated versus conventional method of culture and plate count, obtaining a very good agreement. The EMI is simple, fast and economical to detect and quantify ETEC F4 in swine feces samples, being thus a valuable tool in swine production. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteomic analysis of enterotoxigenic Escherichia coli (ETEC) in neutral and alkaline conditions.

PubMed

Gonzales-Siles, Lucia; Karlsson, Roger; Kenny, Diarmuid; Karlsson, Anders; Sjöling, Åsa

2017-01-07

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in children and travelers to endemic areas. Secretion of the heat labile AB 5 toxin (LT) is induced by alkaline conditions. In this study, we determined the surface proteome of ETEC exposed to alkaline conditions (pH 9) as compared to neutral conditions (pH 7) using a LPI Hexalane FlowCell combined with quantitative proteomics. Relative quantitation with isobaric labeling (TMT) was used to compare peptide abundance and their corresponding proteins in multiple samples at MS/MS level. For protein identification and quantification samples were analyzed using either a 1D-LCMS or a 2D-LCMS approach. Strong up-regulation of the ATP synthase operon encoding F1Fo ATP synthase and down-regulation of proton pumping proteins NuoF, NuoG, Ndh and WrbA were detected among proteins involved in regulating the proton and electron transport under alkaline conditions. Reduced expression of proteins involved in osmotic stress was found at alkaline conditions while the Sec-dependent transport over the inner membrane and outer membrane protein proteins such as OmpA and the β-Barrel Assembly Machinery (BAM) complex were up-regulated. ETEC exposed to alkaline environments express a specific proteome profile characterized by up-regulation of membrane proteins and secretion of LT toxin. Alkaline microenvironments have been reported close to the intestinal epithelium and the alkaline proteome may hence represent a better view of ETEC during infection.

Cost-benefit of WC/rBS oral cholera vaccine for vaccination against ETEC-caused travelers' diarrhea.

PubMed

Lundkvist, Jonas; Steffen, Robert; Jönsson, Bengt

2009-01-01

The most common infectious health problem encountered by travelers to countries in the developing region is travelers' diarrhea (TD), with enterotoxigenic Escherichia coli (ETEC) being the most common pathogen isolated. Although mild in most cases, the disease still leads to the loss of a significant part of a vacation or business trip. There is currently a lack of knowledge about the costs in relation to the benefits of vaccination against TD caused by ETEC, and the purposes of this study were to estimate and develop a cost-benefit analysis of vaccination using whole-cell/recombinant-B-subunit oral cholera vaccine. The consequences of the vaccination were identified and quantified in monetary terms. The cost-benefits for leisure and business travelers were assessed separately. The value of the travel was separated into the cost of the trip and of lost leisure time/business opportunities. A person with TD was in base case estimated to lose on average 3.5 days of a 7-day leisure trip and 2.5 days of a 4-day business trip. Results are presented for a Canadian traveler to endemic areas in year 2007 in US$. The average cost of a TD event was estimated at $1,460 and $1,996 for leisure and business travelers, respectively. The net value of the vaccination, however, varied with the risk of the disease. Through extensive literature searches, an updated ETEC map illustrating the proportion of ETEC-caused TD was created. The analysis indicated that vaccination would be considered cost-effective at incidence rates of ETEC-caused TD above about 13 and 9% for leisure and business travelers, respectively. It is, however, important to keep in mind that it is the value of the travel for the individual traveler that will decide if the vaccination provides good value for money.

Histomorphometric characteristics of immune cells in small intestine of pigs perorally immunized with vaccine candidate F18ac nonenterotoxigenic E. coli strain.

PubMed

Kovšca Janjatović, A; Lacković, G; Božić, F; Spoljarić, D; Popović, M; Valpotić, H; Vijtiuk, N; Pavičić, Z; Valpotić, I

2009-12-29

Colidiarrhea and colienterotoxemia caused by F4(+) and/or F18(+) enterotoxigenic E. coli (ETEC) strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac(+) non-ETEC vaccine candidate strain against challenge infection with F4ac(+) ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs.We also evaluated levamisole as an immune response modifier (IRM) and its adjuvanticity when given in the combination with the experimental vaccine. The pigs were parenterally immunized with either levamisole (at days -2, -1 and 0) or with levamisole and perorally given F18ac(+) non-ETEC strain (at day 0), and challenged with F4ac(+) ETEC strain 7 days later.At day 13 the pigs were euthanatized and sampled for immunohistological/histomorphometrical analyses. Lymphoid CD3(+), CD45RA(+), CD45RC(+), CD21(+), IgA(+) and myeloid SWC3(+) cell subsets were identified in jejunal and ileal epithelium, lamina propria and Peyer's patches using the avidin-biotin complex method, and their numbers were determined by computer-assisted histomorphometry. Quantitative immunophenotypic analyses showed that levamisole treated pigs had highly increased numbers of jejunal CD3(+), CD45RC(+) and SWC3(+) cells (p<0.05) as compared to those recorded in nontreated control pigs.In the ileum of these pigs we have recorded that only CD21(+) cells were significantly increased (p<0.01). The pigs that were treated with levamisole adjuvanted experimental vaccine had significantly increased numbers of all tested cell subsets in both segments of the small intestine. It was concluded that levamisole adjuvanted F18ac(+) non-ETEC vaccine was a requirement for the elicitation of protective gut immunity in this model; nonspecific immunization with levamisole was less effective, but confirmed its potential as an IRM.

Immunobiotic Lactobacillus jensenii Elicits Anti-Inflammatory Activity in Porcine Intestinal Epithelial Cells by Modulating Negative Regulators of the Toll-Like Receptor Signaling Pathway

PubMed Central

Shimazu, Tomoyuki; Villena, Julio; Tohno, Masanori; Fujie, Hitomi; Hosoya, Shoichi; Shimosato, Takeshi; Aso, Hisashi; Suda, Yoshihito; Kawai, Yasushi; Saito, Tadao; Makino, Seiya; Ikegami, Shuji; Itoh, Hiroyuki

2012-01-01

The effect of Lactobacillus jensenii TL2937 on the inflammatory immune response triggered by enterotoxigenic Escherichia coli (ETEC) and lipopolysaccharide (LPS) in a porcine intestinal epitheliocyte cell line (PIE cells) was evaluated. Challenges with ETEC or LPS elicited Toll-like receptor 4 (TLR4)-mediated inflammatory responses in cultured PIE cells, indicating that our cell line may be useful for studying inflammation in the guts of weaning piglets. In addition, we demonstrated that L. jensenii TL2937 attenuated the expression of proinflammatory cytokines and chemokines caused by ETEC or LPS challenge by downregulating TLR4-dependent nuclear factorκB (NF-κB) and mitogen-activated protein kinase (MAPK) activation. Furthermore, we demonstrated that L. jensenii TL2937 stimulation of PIE cells upregulated three negative regulators of TLRs: A20, Bcl-3, and MKP-1, deepening the understanding of an immunobiotic mechanism of action. L. jensenii TL2937-mediated induction of negative regulators of TLRs would have a substantial physiological impact on homeostasis in PIE cells, because excessive TLR inflammatory signaling would be downregulated. These results indicated that PIE cells can be used to study the mechanisms involved in the protective activity of immunobiotics against intestinal inflammatory damage and may provide useful information for the development of new immunologically functional feeds that help to prevent inflammatory intestinal disorders, including weaning-associated intestinal inflammation. PMID:22083706

A standardised challenge model with an enterotoxigenic F4+ Escherichia coli strain in piglets assessing clinical traits and faecal shedding of fae and est-II toxin genes.

PubMed

Spitzer, Franz; Vahjen, Wilfried; Pieper, Robert; Martinez-Vallespin, Beatriz; Zentek, Jürgen

2014-12-01

This study evaluated the effect of five feed additives on post weaning diarrhoea (PWD) in piglets challenged 3 d after weaning with an enterotoxigenic Escherichia coli strain (ETEC). In three experimental runs, a total of 84 piglets was weaned at 21 days of age and randomly assigned to seven treatments. As dietary treatment, piglets were fed a basal diet or diets with addition of bovine colostrum (0.2%), pineapple stem extract containing bromelain (0.2%), an autolysed yeast preparation (Saccharomyces cerevisiae) (0.1%), a combination of organic acids (0.7%) and a phytogenic product with thyme essential oil (0.015%). A porcine ETEC, serotype O149:K91:K88ac was given twice via oral infection on day 3 after weaning at 10(10) colony forming units/animal. One group of piglets was fed the basal diet without ETEC challenge. Traits included clinical sores, body temperature, faecal scoring and determination of faecal dry matter and the shedding of fae and est-II ETEC toxin genes. After weaning, non-challenged control piglets did not show signs of diarrhoea or impaired health, while the majority of infected piglets had a drop in body temperature, signs of diarrhoea and impaired general health. Mortality, the decrease of faecal dry matter and shedding of the toxin genes fae and est-II were not affected by the different additives. In conclusion, the ETEC challenge model induced distinct clinical signs of PWD in piglets, but the tested feed additives had no preventive effect under these conditions.

Performance testing and results of the first Etec CORE-2564

NASA Astrophysics Data System (ADS)

Franks, C. Edward; Shikata, Asao; Baker, Catherine A.

1993-03-01

In order to be able to write 64 megabit DRAM reticles, to prepare to write 256 megabit DRAM reticles and in general to meet the current and next generation mask and reticle quality requirements, Hoya Micro Mask (HMM) installed in 1991 the first CORE-2564 Laser Reticle Writer from Etec Systems, Inc. The system was delivered as a CORE-2500XP and was subsequently upgraded to a 2564. The CORE (Custom Optical Reticle Engraver) system produces photomasks with an exposure strategy similar to that employed by an electron beam system, but it uses a laser beam to deliver the photoresist exposure energy. Since then the 2564 has been tested by Etec's standard Acceptance Test Procedure and by several supplementary HMM techniques to insure performance to all the Etec advertised specifications and certain additional HMM requirements that were more demanding and/or more thorough than the advertised specifications. The primary purpose of the HMM tests was to more closely duplicate mask usage. The performance aspects covered by the tests include registration accuracy and repeatability; linewidth accuracy, uniformity and linearity; stripe butting; stripe and scan linearity; edge quality; system cleanliness; minimum geometry resolution; minimum address size and plate loading accuracy and repeatability.

Comparison of three patterns of feed supplementation with live Saccharomyces cerevisiae yeast on postweaning diarrhea, health status, and blood metabolic profile of susceptible weaning pigs orally challenged with Escherichia coli F4ac.

PubMed

Trevisi, P; Colombo, M; Priori, D; Fontanesi, L; Galimberti, G; Calò, G; Motta, V; Latorre, R; Fanelli, F; Mezzullo, M; Pagotto, U; Gherpelli, Y; D'Inca, R; Bosi, P

2015-05-01

The development of effective feeding strategies to reduce the detrimental effect of enterotoxigenic F4ac (ETEC) plays a crucial role in reducing the occurrence of therapeutic intervention with antibiotics in livestock. The ability of CNCM I-4407 (SCC), supplied in different patterns to counteract ETEC infection in weaned pigs, was evaluated. Fifty pigs weaned at 24 d were then divided into 5 groups: control (CO), CO + colistin (AB), CO + 5 × 10(10) cfu of SCC/ kg feed, from d 0 to 21 (PR), CO + 5 × 10(10) cfu of SCC/ kg feed from d 7 to 11 (CM), and CO + 1 shot of 2 × 10(11) cfu of SCC when the first diarrhea appeared (CU). On d 7 postweaning, all the pigs were orally challenged with 10(8) cfu of ETEC. Blood samples were taken from the pigs (d 7, 8, 12, and 21) while the fecal excretion of ETEC was assessed on d 7 and 10. Fecal consistency was scored from 12 h before infection to 144 h postinfection (p.i.). On d 21, the pigs were sacrificed. The in vitro adhesion test on the intestinal villi confirmed individual susceptibility to ETEC, excluding the presence of resistant pigs. Growth performance did not differ between the treatments. Mortality was reduced in the AB group (P< 0.01) and, marginally, in the PR group (P = 0.089) when compared to the CO group. The CO group had a higher fecal score than AB in the period of observation (from P = 0.01 to P< 0.001). Yeast administration reduced the fecal score when compared to the CO group 12 and 48 h p.i. (P = 0.04). Total IgA never differed among the treatments, but the ETEC-specific IgA concentration was lower in the AB group than in CO (P = 0.04) at d 12. Four days p.i., the pigs fed live yeast had reduced ETEC excretion compared with the CO pigs (P = 0.05). Blood concentrations of dodecenoyl-L-carnitine (P < 0.01), glutaryl-L-carnitine/hydroxyhex¬anoyl-L-carnitine, phosphatidylcholine diacyl and phosphatidylcholine diacyl (P = 0.01 and P< 0.01, respectively), and α-amino adipic acid (P < 0.01) were reduced in the AB group compared to the CO group; PR + CM reduced the concentration of sphingomyelin-ceramide (P = 0.02) and increased the concentration of decadienyl-L-carnitine (C10:2; P= 0.02) vs. CO. The CM group had an increased concentration of C10:2 (P < 0.01) compared to the PR group. In conclusion, the administration of live yeast, even in concomitance with ETEC infections, reduces pig illness and mortality. The strain of SCC tested did not show a therapeutic effect.

Young Pigs Consuming Lysozyme Transgenic Goat Milk Are Protected from Clinical Symptoms of Enterotoxigenic Escherichia coli Infection.

PubMed

Garas, Lydia C; Cooper, Caitlin A; Dawson, Matthew W; Wang, Jane-Ling; Murray, James D; Maga, Elizabeth A

2017-11-01

Background: Diarrheal diseases in infancy and childhood are responsible for substantial morbidity and mortality in developing nations. Lysozyme, an antimicrobial component of human milk, is thought to play a role in establishing a healthy intestinal microbiota and immune system. Consumption of breast milk has been shown to prevent intestinal infections and is a recommended treatment for infants with diarrhea. Objective: This study aimed to examine the ability of lysozyme-rich goat milk to prevent intestinal infection. Methods: Six-week-old Hampshire-Yorkshire pigs were assigned to treatment groups balanced for weight, sex, and litter and were fed milk from nontransgenic control goats (GM group) or human lysozyme transgenic goats (hLZM group) for 2 wk before they were challenged with porcine-specific enterotoxigenic Escherichia coli (ETEC). Fecal consistency, complete blood counts, intestinal histology, and microbial populations were evaluated. Results: Pigs in the hLZM group had less severe diarrhea than did GM pigs at 24 and 48 h after ETEC infection ( P = 0.01 and 0.05, respectively), indicating a less severe clinical disease state. Relative to baseline, postmilk hLZM pigs had 19.9% and 137% enrichment in fecal Bacteroidetes ( P = 0.028) and Paraprevotellaceae ( P = 0.003), respectively, and a 93.8% reduction in Enterobacteriaceae ( P = 0.007), whereas GM pigs had a 60.9% decrease in Lactobacillales ( P = 0.003) and an 83.3% enrichment in Burkholderiales ( P = 0.010). After ETEC infection, hLZM pigs tended to have lower amounts (68.7% less) of fecal Enterobacteriaceae than did GM pigs ( P = 0.058). There were 83.1% fewer bacteria translocated into the mesenteric lymph nodes of hLZM pigs than into those of GM pigs ( P = 0.039), and hLZM pigs had 34% lower mucin 1 and 61% higher tumor necrosis factor-α expression in the ileum than did GM pigs ( P = 0.046 and 0.034, respectively). Conclusion: Results of this study indicate that human lysozyme milk consumption before and during ETEC infection has a positive effect on clinical disease, intestinal mucosa, and gut microbiota in young pigs. © 2017 American Society for Nutrition.

Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial.

PubMed

Frech, Sarah A; Dupont, Herbert L; Bourgeois, A Louis; McKenzie, Robin; Belkind-Gerson, Jaime; Figueroa, Jose F; Okhuysen, Pablo C; Guerrero, Norma H; Martinez-Sandoval, Francisco G; Meléndez-Romero, Juan Hm; Jiang, Zhi-Dong; Asturias, Edwin J; Halpern, Jane; Torres, Olga R; Hoffman, Ana S; Villar, Christina P; Kassem, Raniya N; Flyer, David C; Andersen, Bo H; Kazempour, Kazem; Breisch, Sally A; Glenn, Gregory M

2008-06-14

Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the rate of diarrhoea attacks, safety, and feasibility of a vaccine containing heat-labile enterotoxin (LT) from ETEC delivered to the skin by patch in travellers to Mexico and Guatemala. In this phase II study, healthy adults (aged 18-64 years) who planned to travel to Mexico or Guatemala and had access to a US regional vaccination centre were eligible. A centralised randomisation code was used for allocation, which was masked to participants and site staff. Primary endpoints were to investigate the field rate of ETEC diarrhoea, and to assess the safety of heat-labile toxins from E coli (LT) delivered via patch. Secondary endpoints included vaccine efficacy against travellers' diarrhoea and ETEC. Participants were vaccinated before travel, with two patches given 2-3 weeks apart. Patches contained either 37.5 mug of LT or placebo. Participants tracked stool output on diary cards in country and provided samples for pathogen identification if diarrhoea occurred. Diarrhoea was graded by the number of loose stools in 24 h: mild (three), moderate (four or five), and severe (at least six). Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT00516659. Recruitment closed after 201 participants were assigned patches. 178 individuals received two vaccinations and travelled and 170 were analysed. 24 (22%) of 111 placebo recipients had diarrhoea, of whom 11 (10%) had ETEC diarrhoea. The vaccine was safe and immunogenic. The 59 LT-patch recipients were protected against moderate-to-severe diarrhoea (protective efficacy [PE] 75%, p=0.0070) and severe diarrhoea (PE 84%, p=0.0332). LT-patch recipients who became ill had shorter episodes of diarrhoea (0.5 days vs 2.1 days, p=0.0006) with fewer loose stools (3.7 vs 10.5, p<0.0001) than placebo. Travellers' diarrhoea is a common ailment, with ETEC diarrhoea illness occurring in 10% of cases. The vaccine patch is safe and feasible, with benefits to the rate and severity of travellers' diarrhoea.

Influence of host interleukin-10 polymorphisms on development of traveler's diarrhea due to heat-labile enterotoxin-producing Escherichia coli in travelers from the United States who are visiting Mexico.

PubMed

Flores, Jose; DuPont, Herbert L; Lee, Stephanie A; Belkind-Gerson, Jaime; Paredes, Mercedes; Mohamed, Jamal A; Armitige, Lisa Y; Guo, Dong-Chuan; Okhuysen, Pablo C

2008-08-01

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position -1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position -819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position -592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD.

Characterization of Diarrheagenic Escherichia coli Isolated in Organic Waste Products (Cattle Fecal Matter, Manure and, Slurry) from Cattle's Markets in Ouagadougou, Burkina Faso.

PubMed

Bako, Evariste; Kagambèga, Assèta; Traore, Kuan Abdoulaye; Bagre, Touwendsida Serge; Ibrahim, Hadiza Bawa; Bouda, Soutongnooma Caroline; Bonkoungou, Isidore Juste Ouindgueta; Kaboré, Saidou; Zongo, Cheikna; Traore, Alfred Sababenejo; Barro, Nicolas

2017-09-22

Cattle farming can promote diarrheal disease transmission through waste, effluents or cattle fecal matter. The study aims to characterize the diarrheagenic Escherichia coli (DEC) isolated from cattle feces, manure in the composting process and slurry, collected from four cattle markets in Ouagadougou. A total of 585 samples (340 cattle feces, 200 slurries and 45 manures in the composting process) were collected from the four cattle markets between May 2015 and May 2016. A multiplex Polymerase Chain Reaction (PCR), namely 16-plex PCR, was used to screen simultaneously the virulence genes specific for shiga toxin-producing E. coli (STEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC) and enteroaggregative E. coli (EAEC). DEC was detected in 10.76% of samples. ETEC was the most prevalent (9.91%). STEC and EAEC have been observed with the same rate (0.51%). ETEC were detected in 12.64% of cattle feces, in 6.66% of manure in the composting process and in 5% of slurry. STEC were detected in 0.58% of cattle feces and in 2.22% of manure in the composting process. EAEC was detected only in 1% of slurry and in 2.22% of manure in the composting process. ETEC strains were identified based on estIa gene and/or estIb gene and/or elt gene amplification. Of the 58 ETEC, 10.34% contained astA , 17.24% contained elt , 3.44% contained estIa and 79.31% contained estIb . The two positive EAEC strains contained only the aggR gene, and the third was positive only for the pic gene. The results show that effluent from cattle markets could contribute to the spreading of DEC in the environment in Burkina Faso.

Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and rotavirus

PubMed Central

2013-01-01

Background Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the understanding of diarrheal disorders and management strategies, globally nearly 750,000 children die annually as a consequence of diarrhea. Methods We conducted a systematic review of the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes. The estimated effect of cholera, shigella, Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules. Results A total of 24 papers were selected and analyzed for all the four vaccines. Based on the evidence, we propose a 74% mortality reduction in rotavirus specific mortality, 52% reduction in cholera incidence due to their respective vaccines. We did not find sufficient evidence and a suitable outcome to project mortality reductions for cholera, ETEC and shigella in children under 5 years. Conclusion Vaccines for rotavirus and cholera have the potential to reduce diarrhea morbidity and mortality burden. But there is no substantial evidence of efficacy for ETEC and shigella vaccines, although several promising vaccine concepts are moving from the development and testing pipeline towards efficacy and Phase 3 trials. PMID:24564510

Prospective study of pathogens in asymptomatic travellers and those with diarrhoea: aetiological agents revisited.

PubMed

Lääveri, T; Antikainen, J; Pakkanen, S H; Kirveskari, J; Kantele, A

2016-06-01

Travellers' diarrhoea (TD) remains the most frequent health problem encountered by visitors to the (sub)tropics. Traditional stool culture identifies the pathogen in only 15% of cases. Exploiting PCR-based methods, we investigated TD pathogens with a focus on asymptomatic travellers and severity of symptoms. Pre- and post-travel stools of 382 travellers with no history of antibiotic use during travel were analysed with a multiplex quantitative PCR for Salmonella, Yersinia, Campylobacter, Shigella, Vibrio cholerae and five diarrhoeagenic Escherichia coli: enteroaggregative (EAEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC) and enteroinvasive (EIEC). The participants were categorized by presence/absence of TD during travel and on return, and by severity of symptoms. A pathogen was indentified in 61% of the asymptomatic travellers, 83% of those with resolved TD, and 83% of those with ongoing TD; 25%, 43% and 53% had multiple pathogens, respectively. EPEC, EAEC, ETEC and Campylobacter associated especially with ongoing TD symptoms. EAEC and EPEC proved more common than ETEC. To conclude, modern methodology challenges our perception of stool pathogens: all pathogens were common both in asymptomatic and symptomatic travellers. TD has a multibacterial nature, but diarrhoeal symptoms mostly associate with EAEC, EPEC, ETEC and Campylobacter. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characterization of enterotoxigenic Escherichia coli strains isolated from the massive multi-pathogen gastroenteritis outbreak in the Antofagasta region following the Chilean earthquake, 2010.

PubMed

Montero, David; Vidal, Maricel; Pardo, Mirka; Torres, Alexia; Kruger, Eduardo; Farfán, Mauricio; O'Ryan, Miguel; Luo, Qingwei; Fleckenstein, James; Del Canto, Felipe; Vidal, Roberto

2017-08-01

In March 2010, a massive outbreak of gastroenteritis started in the region of Antofagasta (northern Chile). The outbreak was mainly attributed to Norovirus genogroup II although ETEC strains were also isolated with high frequency from clinical samples. We review this outbreak and determined that ETEC was an underestimated etiologic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

The Epidemiology of Travelers’ Diarrhea in Incirlik, Turkey: A Region with a Predominance of Heat-Stabile Toxin Producing Enterotoxigenic Escherichia coli

DTIC Science & Technology

2010-01-01

identification of typical enteric bacteria (e.g., Campylobacter spp.. Shigella spp., Salmonella spp., and Vibrio spp.) (Bopp et al., 1 999; Farmer...stool specimens at initial presentation Pathogen ETEC" Campylobacter spp." Plesiomonas shigelloidesh Shigella spp." Nontyphoidal Salmonella spp...2 with nontyphoidal Salmonella spp., and I with both Shigella spp. and G. Iamblia). Approximately 70% of subjects with only ETEC isolated from

Lactobacillus delbrueckii TUA4408L and its extracellular polysaccharides attenuate enterotoxigenic Escherichia coli-induced inflammatory response in porcine intestinal epitheliocytes via Toll-like receptor-2 and 4.

PubMed

Wachi, Satoshi; Kanmani, Paulraj; Tomosada, Yohsuke; Kobayashi, Hisakazu; Yuri, Toshihito; Egusa, Shintaro; Shimazu, Tomoyuki; Suda, Yoshihito; Aso, Hisashi; Sugawara, Makoto; Saito, Tadao; Mishima, Takashi; Villena, Julio; Kitazawa, Haruki

2014-10-01

Immunobiotics are known to modulate intestinal immune responses by regulating Toll-like receptor (TLR) signaling pathways, which are responsible for the induction of cytokines and chemokines in response to microbial-associated molecular patterns. However, little is known about the immunomodulatory activity of compounds or molecules from immunobiotics. We evaluated whether Lactobacillus delbrueckii subsp. delbrueckii TUA4408L (Ld) or its extracellular polysaccharide (EPS): acidic EPS (APS) and neutral EPS (NPS), modulated the response of porcine intestinal epitheliocyte (PIE) cells against Enterotoxigenic Escherichia coli (ETEC) 987P. The roles of TLR2, TLR4, and TLR negative regulators in the immunoregulatory effects were also studied. ETEC-induced inflammatory cytokines were downregulated when PIE cells were prestimulated with both Ld or EPSs. Ld, APS, and NPS inhibited ETEC mediated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation by upregulating TLR negative regulators. The capability of Ld to suppress inflammatory cytokines was diminished when PIE cells were blocked with anti-TLR2 antibody, while APS failed to suppress inflammatory cytokines when cells were treated with anti-TLR4 antibody. Induction of Ca²⁺ fluxes in TLR knockdown cells confirmed that TLR2 plays a principal role in the immunomodulatory action of Ld, while the activity of APS is mediated by TLR4. In addition, NPS activity depends on both TLR4 and TLR2. Ld and its EPS have the potential to be used for the development of anti-inflammatory functional foods to prevent intestinal diseases in both humans and animals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oral immunization of mice with plant-derived fimbrial adhesin FaeG induces systemic and mucosal K88ad enterotoxigenic Escherichia coli-specific immune responses.

PubMed

Liang, Wanqi; Huang, Yahong; Yang, Xinghong; Zhou, Zhiai; Pan, Aihu; Qian, Bingjun; Huang, Cheng; Chen, Jianxiu; Zhang, Dabing

2006-04-01

The importance of adhesins in pathogenicity has resulted in them being useful targets in the defense against bacterial infections. To produce edible vaccines against piglet diarrhea caused by enterotoxigenic Escherichia coli (ETEC), plants were genetically engineered to produce recombinant fimbrial adhesin FaeG. To evaluate the efficacy of the edible vaccine FaeG in mice, the soluble protein extracts were examined by about 15 microg recombinant FaeG for each oral immunization dose per mouse. After four doses of vaccination, both IgG and IgA antibodies specific to K88ad fimbriae were elicited in serum, and specific IgA antibodies were also evoked in feces of the immunized mice. Moreover, visible K88ad ETEC agglutination by the specific serum from the immunized mice was observed, implying the antibody was highly specific and effective. Results from an in vitro villous-adhesion assay further confirmed that serum antibodies of the immunized mice could inhibit K88ad ETEC from adhering to pig intestinal receptors, further demonstrating the oral immune efficacy of the plant-derived FaeG. This study provides a promising, noninvasive method for vaccinating swine by feeding supplements of transgenic plant. Moreover, the low cost and ease of delivery of this edible ETEC vaccine will facilitate its application in economically disadvantaged regions.

F4 (K88) fimbrial adhesin FaeG expressed in alfalfa reduces F4+ enterotoxigenic Escherichia coli excretion in weaned piglets.

PubMed

Joensuu, J J; Verdonck, F; Ehrström, A; Peltola, M; Siljander-Rasi, H; Nuutila, A M; Oksman-Caldentey, K-M; Teeri, T H; Cox, E; Goddeeris, B M; Niklander-Teeri, V

2006-03-20

Transgenic plants are attractive bioreactors to large-scale production of recombinant proteins because of their relatively low cost. This study reports for the first time the use of transgenic plants to reduce enterotoxigenic Escherichia coli (ETEC) excretion in its natural host species. The DNA sequence encoding the major subunit and adhesin FaeG of F4+ ETEC was transformed into edible alfalfa plants. Targeting of FaeG production to chloroplasts led to FaeG levels of up to 1% of the total soluble protein fraction of the transgenic alfalfa. Recombinant plant-produced FaeG (pFaeG) remained stable for 2 years when the plant material was dried and stored at room temperature. Intragastric immunization of piglets with pFaeG induced a weak F4-specific humoral response. Co-administration of pFaeG and the mucosal adjuvant cholera toxin (CT) enhanced the immune response against FaeG, reflected a better induction of an F4-specific immune response. In addition, the intragastric co-administration of CT with pFaeG significantly reduced F4+ E. coli excretion following F4+ ETEC challenge as compared with pigs that had received nontransgenic plant material. In conclusion, transgenic plants producing the FaeG subunit protein could be used for production and delivery of oral vaccines against F4+ ETEC infections.

l-Theanine prevents ETEC-induced liver damage by reducing intrinsic apoptotic response and inhibiting ERK1/2 and JNK1/2 signaling pathways.

PubMed

Gong, Zhihua; Liu, Qiuling; Lin, Ling; Deng, Yanli; Cai, Shuxian; Liu, Zunying; Zhang, Sheng; Xiao, Wenjun; Xiong, Shuo; Chen, Dong

2018-01-05

l-Theanine (LTA; γ-glutamylethylamide), a peculiar non-protein-derived amino acid isolated from tea, is widely used as a functional ingredient and dietary supplement. l-Theanine has been confirmed to have hepatoprotective effects, but the underlying mechanism remains unknown. This study investigated the protective effect of l-Theanine-in vivo, using an enterotoxigenic Escherichia coli (ETEC)-infected mouse model. l-Theanine significantly decreased the elevated serum activities of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT), two biomarkers of hepatic impairment. This was consistent with histopathological images from the microscopic observation of liver tissue. In addition, l-theanine significantly increased the mRNA and protein expression of Bcl-2 and decreased the expression of Bax, anti- and pro-apoptotic molecules, respectively, compared with levels in the ETEC control group. The expression of cleaved caspase-3 protein in the group pre-treated with l-theanine was significantly lower than that in the ETEC group. Additionally, decreases in extracellular signal-regulated kinase (ERK1/2) and c-Jun NH 2 -terminal kinase(JNK1/2) MAPK phosphorylation were observed in the l-theanine pre-treated group. Our study demonstrates that l-theanine possesses anti-apoptotic activity, which can be attributed to suppression of the intrinsic mitochondria-mediated apoptosis and MAPK phosphorylation signaling pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Adjuvant effect of Gantrez®AN nanoparticles during oral vaccination of piglets against F4+enterotoxigenic Escherichia coli.

PubMed

Vandamme, Katrien; Melkebeek, Vesna; Vesna, Melkebeek; Cox, Eric; Eric, Cox; Remon, Jean Paul; Paul, Remon Jean; Vervaet, Chris; Chris, Vervaet

2011-02-15

In this study, the adjuvanticity of methylvinylether-co-maleic anhydride (Gantrez(®)AN) nanoparticles (NP) was investigated in an oral immunisation experiment of pigs against F4+enterotoxigenic Escherichia coli (F4+ETEC). In addition, Wheat Germ Agglutinin (WGA)-coating of the nanoparticles was tested for enterocyte-targeting. Pigs were either vaccinated with F4 fimbriae, F4 encapsulated in Gantrez(®)AN NP, F4 encapsulated in Gantrez(®)AN NP coated with WGA or F4 fimbriae mixed with empty Gantrez(®)AN NP. Only vaccination with the combination of F4 mixed with empty Gantrez(®)AN NP improved protection against F4+ETEC infection. In addition, vaccination with this formulation also resulted in an F4-specific serum antibody response prior to F4+ETEC challenge. Encapsulation of F4 in Gantrez(®)AN NP only raised the serum antibody response after F4+ETEC challenge compared to soluble F4, but did not improve protection, whereas WGA-coating almost completely abolished the serum antibody response. These data indicate that nanoparticle effects after F4 encapsulation were of lesser importance for the adjuvant effect of Gantrez(®)AN NP, contrarily to the reactivity of the Gantrez(®)AN polymer used to prepare the nanoparticles. Copyright © 2010 Elsevier B.V. All rights reserved.

Influence of Host Interleukin-10 Polymorphisms on Development of Traveler's Diarrhea Due to Heat-Labile Enterotoxin-Producing Escherichia coli in Travelers from the United States Who Are Visiting Mexico▿

PubMed Central

Flores, Jose; DuPont, Herbert L.; Lee, Stephanie A.; Belkind-Gerson, Jaime; Paredes, Mercedes; Mohamed, Jamal A.; Armitige, Lisa Y.; Guo, Dong-Chuan; Okhuysen, Pablo C.

2008-01-01

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position −1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position −819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position −592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD. PMID:18579697

Characterization of Diarrheagenic Escherichia coli Isolated in Organic Waste Products (Cattle Fecal Matter, Manure and, Slurry) from Cattle’s Markets in Ouagadougou, Burkina Faso

PubMed Central

Bako, Evariste; Kagambèga, Assèta; Traore, Kuan Abdoulaye; Bagre, Touwendsida Serge; Ibrahim, Hadiza Bawa; Bouda, Soutongnooma Caroline; Bonkoungou, Isidore Juste Ouindgueta; Kaboré, Saidou; Zongo, Cheikna; Traore, Alfred Sababenejo; Barro, Nicolas

2017-01-01

Cattle farming can promote diarrheal disease transmission through waste, effluents or cattle fecal matter. The study aims to characterize the diarrheagenic Escherichia coli (DEC) isolated from cattle feces, manure in the composting process and slurry, collected from four cattle markets in Ouagadougou. A total of 585 samples (340 cattle feces, 200 slurries and 45 manures in the composting process) were collected from the four cattle markets between May 2015 and May 2016. A multiplex Polymerase Chain Reaction (PCR), namely 16-plex PCR, was used to screen simultaneously the virulence genes specific for shiga toxin-producing E. coli (STEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC) and enteroaggregative E. coli (EAEC). DEC was detected in 10.76% of samples. ETEC was the most prevalent (9.91%). STEC and EAEC have been observed with the same rate (0.51%). ETEC were detected in 12.64% of cattle feces, in 6.66% of manure in the composting process and in 5% of slurry. STEC were detected in 0.58% of cattle feces and in 2.22% of manure in the composting process. EAEC was detected only in 1% of slurry and in 2.22% of manure in the composting process. ETEC strains were identified based on estIa gene and/or estIb gene and/or elt gene amplification. Of the 58 ETEC, 10.34% contained astA, 17.24% contained elt, 3.44% contained estIa and 79.31% contained estIb. The two positive EAEC strains contained only the aggR gene, and the third was positive only for the pic gene. The results show that effluent from cattle markets could contribute to the spreading of DEC in the environment in Burkina Faso. PMID:28937656

Characterization and Virulence Assessment of Two 091:821 Enterohemorrhagic Escherichia Coli Isolates

DTIC Science & Technology

1993-04-30

stable toxin (ST) . ETEC cause profuse watery diarrhea similar to the diarrhea caused by Vibrio cholerae infection (Sack, 1975). EIEC, unlike ETEC...Fr •• ley, R. B. Sack, W. B. Cr •• ch, A. Z. Itapikian, B. J. Gang_ro ••• 1976. Travelers diarrhea in Mexico . A prospective study of physicians...p.153- 158 . Proceedings of the U. S.-Japan 27th Joint Conference on Cholera and Related Diarrheal Diseases. Virginia. Charlottesville, Yu, J

Concurrent Outbreak of Norovirus Genotype I and Enterotoxigenic Escherichia coli on a U.S. Navy Ship following a Visit to Lima, Peru

PubMed Central

Gonzaga, Victor E.; Ramos, Mariana; Maves, Ryan C.; Freeman, Randal; Montgomery, Joel M.

2011-01-01

An outbreak of norovirus (NoV) genotype I and Enterotoxigenic Escherichia coli (ETEC) occurred among US Navy Ship personnel following a visit to Lima, Peru, in June 2008. Visiting a specific area in Lima was significantly associated with illness. While ETEC and NoV are commonly recognized as causative agents of outbreaks, co-circulation of both pathogens has been rarely observed in shipboard outbreaks. PMID:21713034

Pre-Clinical Testing of a Real-Time PCR Assay for Diahhreal Disease Agent Cryptosporidium

DTIC Science & Technology

2014-05-16

ETEC, Shigella , and CR assays are shown in Table 4. Standard curves are shown in Figures 1 - 5. Limit of detection estimation derived from standard...curve are shown in Table 5. These data include results from both ‘JBAIDS ETEC/ Shigella ’ and ‘JBAIDS Cryptospordium’ projects. Standard cuve for... Shigella -ipaH 0.088 1.5 × 10 8 Isolates of Cryptosporidium parvum from Waterborne Inc., using Qiagen extraction kit Parasite NanoDrop

An outbreak of enterotoxigenic Escherichia coli (ETEC) infection in Norway, 2012: a reminder to consider uncommon pathogens in outbreaks involving imported products.

PubMed

MacDonald, E; Møller, K E; Wester, A L; Dahle, U R; Hermansen, N O; Jenum, P A; Thoresen, L; Vold, L

2015-02-01

We investigated an outbreak of gastroenteritis following a Christmas buffet served on 4-9 December 2012 to ~1300 hotel guests. More than 300 people were reported ill in initial interviews with hotel guests. To identify possible sources of infection we conducted a cohort investigation through which we identified 214 probable cases. Illness was associated with consumption of scrambled eggs (odds ratio 9·07, 95% confidence interval 5·20-15·84). Imported chives added fresh to the scrambled eggs were the suspected source of the outbreak but were unavailable for testing. Enterotoxigenic Escherichia coli (ETEC) infection was eventually confirmed in 40 hotel guests. This outbreak reinforces that ETEC should be considered in non-endemic countries when the clinical picture is consistent and common gastrointestinal pathogens are not found. Following this outbreak, the Norwegian Food Safety Authority recommended that imported fresh herbs should be heat-treated before use in commercial kitchens.

A Commensal Gone Bad: Complete Genome Sequence of the Prototypical Enterotoxigenic Escherichia coli Strain H10407

DTIC Science & Technology

2010-11-01

and Escherichia ferguso- . TABLE 2. General characteristics of the plasm ids from ETEC strains H10407 and E1392/75 Value in E. c·oli: Characteristic...0352). consetved proteins with unknown func- tions (CDSs 0673 to 0678), a flavoprotein electron transfer system (CDSs 1730 to 1734), the colanic...mediating diarrhea are not chromosomally encoded. indicating that the essential virulence factors are encoded on the plasm ids (61 ). Potentia l

Intestinal Enteroids Model Guanylate Cyclase C-Dependent Secretion Induced by Heat-Stable Enterotoxins.

PubMed

Pattison, Amanda M; Blomain, Erik S; Merlino, Dante J; Wang, Fang; Crissey, Mary Ann S; Kraft, Crystal L; Rappaport, Jeff A; Snook, Adam E; Lynch, John P; Waldman, Scott A

2016-10-01

Enterotoxigenic Escherichia coli (ETEC) causes ∼20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable enterotoxins (STs), which are peptides structurally homologous to paracrine hormones of the intestinal guanylate cyclase C (GUCY2C) receptor. While molecular mechanisms mediating ST-induced intestinal secretion have been defined, advancements in therapeutics have been hampered for decades by the paucity of disease models that integrate molecular and functional endpoints amenable to high-throughput screening. Here, we reveal that mouse and human intestinal enteroids in three-dimensional ex vivo cultures express the components of the GUCY2C secretory signaling axis. ST and its structural analog, linaclotide, an FDA-approved oral secretagog, induced fluid accumulation quantified simultaneously in scores of enteroid lumens, recapitulating ETEC-induced intestinal secretion. Enteroid secretion depended on canonical molecular signaling events responsible for ETEC-induced diarrhea, including cyclic GMP (cGMP) produced by GUCY2C, activation of cGMP-dependent protein kinase (PKG), and opening of the cystic fibrosis transmembrane conductance regulator (CFTR). Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid secretion, providing proof of concept for the utility of this model to screen antidiarrheal agents. Intestinal enteroids offer a unique model, integrating the GUCY2C signaling axis and luminal fluid secretion, to explore the pathophysiology of, and develop platforms for, high-throughput drug screening to identify novel compounds to prevent and treat ETEC diarrheal disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Receptor for the F4 fimbriae of enterotoxigenic Escherichia coli (ETEC).

PubMed

Xia, Pengpeng; Zou, Yajie; Wang, Yiting; Song, Yujie; Liu, Wei; Francis, David H; Zhu, Guoqiang

2015-06-01

Infection with F4(+) enterotoxigenic Escherichia coli (ETEC) responsible for diarrhea in neonatal and post-weaned piglets leads to great economic losses in the swine industry. These pathogenic bacteria express either of three fimbrial variants F4ab, F4ac, and F4ad, which have long been known for their importance in host infection and initiating protective immune responses. The initial step in infection for the bacterium is to adhere to host enterocytes through fimbriae-mediated recognition of receptors on the host cell surface. A number of receptors for ETEC F4 have now been described and characterized, but their functions are still poorly understood. The current review summarizes the latest research addressing the characteristics of F4 fimbriae receptors and the interactions of F4 fimbriae and their receptors on host cells. These include observations that as follows: (1) FaeG mediates the binding activities of F4 and is an essential component of the F4 fimbriae, (2) the F4 fimbrial receptor gene is located in a region of chromosome 13, (3) the biochemical properties of F4 fimbrial receptors that form the binding site of the bacterium are now recognized, and (4) specific receptors confer susceptibility/resistance to ETEC F4 infection in pigs. Characterizing the host-pathogen interaction will be crucial to understand the pathogenicity of the bacteria, provide insights into receptor activation of the innate immune system, and develop therapeutic strategies to prevent this illness.

Development and Efficacy Assessment of an Enteric Coated Porous Tablet Loaded With F4 Fimbriae for Oral Vaccination of Piglets against F4+ Escherichia coli Infections.

PubMed

Srivastava, Atul; Gowda, D V; Madhunapantula, SubbaRao V; Siddaramaiah

2016-01-01

Enterotoxigenic Escherichia coli (ETEC) infection is one of the major causes contributing to the development of diarrhoea and mortality in new born, suckling and newly weaned piglets. To date, no preventive/treatment strategy showed promising results, which could be due to the lack of potent vaccines, and/or due to the development of resistance of ETEC to antibiotics. Therefore, in the present investigation, a novel porous sodium alginate (SA) tablet formulation loaded with F4 fimbriae antigen was developed and tested for efficacy against ETEC infections in piglet models. Precompression parameters of the powder mixes and post compression parameters of tablets have been evaluated and results were found to be satisfactory. Loading of F4 fimbrial antigens into the tablets was achieved by inducing pores in the tablets via the sublimation of camphor followed by incubation with purified F4 fimbriae. The loaded tablets have been coated with Eudragit L100 to protect the F4 fimbriae from (a) highly acidic gastric environment; (b) proteolytic cleavage by pepsin; and (c) to promote subsequent release in the intestine. Evaluation of developed F4 fimbrial tablets in a Pig model demonstrated induction of mucosal immunity, and a significant reduction of F4+ E. coli in faeces. Therefore, F4 fimbriae loaded porous tablets could be a novel oral vaccination candidate to induce mucosal and systemic immunity against ETEC infections.

Lactobacillus amylovorus Inhibits the TLR4 Inflammatory Signaling Triggered by Enterotoxigenic Escherichia coli via Modulation of the Negative Regulators and Involvement of TLR2 in Intestinal Caco-2 Cells and Pig Explants

PubMed Central

Finamore, Alberto; Roselli, Marianna; Imbinto, Ambra; Seeboth, Julie; Oswald, Isabelle P.; Mengheri, Elena

2014-01-01

Inflammation derived from pathogen infection involves the activation of toll-like receptor (TLR) signaling. Despite the established immunomodulatory activities of probiotics, studies relating the ability of such bacteria to inhibit the TLR signaling pathways are limited or controversial. In a previous study we showed that Lactobacillus amylovorus DSM 16698T, a novel lactobacillus isolated from unweaned pigs, protects the intestinal cells from enterotoxigenic Escherichia coli (ETEC) K88 infection through cytokine regulation. In the present study we investigated whether the ability of L. amylovorus to counteract the inflammatory status triggered by ETEC in intestine is elicited through inhibition of the TLR4 signaling pathway. We used the human intestinal Caco-2/TC7 cells and intestinal explants isolated from 5 week-old crossbreed Pietrain/Duroc/Large-White piglets, treated with ETEC, L. amylovorus or L. amylovorus cell free supernatant, either alone or simultaneously with ETEC. Western blot analysis showed that L. amylovorus and its cell free supernatant suppress the activation of the different steps of TLR4 signaling in Caco-2/TC7 cells and pig explants, by inhibiting the ETEC induced increase in the level of TLR4 and MyD88, the phosphorylation of the IKKα, IKKβ, IκBα and NF-κB subunit p65, as well as the over-production of inflammatory cytokines IL-8 and IL-1β. The immunofluorescence analysis confirms the lack of phospho-p65 translocation into the nucleus. These anti-inflammatory effects are achieved through modulation of the negative regulators Tollip and IRAK-M. We also found that L. amylovorus blocks the up-regulation of the extracellular heat shock protein (Hsp)72 and Hsp90, that are critical for TLR4 function. By using anti-TLR2 antibody, we demonstrate that TLR2 is required for the suppression of TLR4 signaling activation. These results may contribute to develop therapeutic interventions using L. amylovorus in intestinal disorders of piglets and humans. PMID:24733511

In Vitro Evaluation of Swine-Derived Lactobacillus reuteri: Probiotic Properties and Effects on Intestinal Porcine Epithelial Cells Challenged with Enterotoxigenic Escherichia coli K88.

PubMed

Wang, Zhilin; Wang, Li; Chen, Zhuang; Ma, Xianyong; Yang, Xuefen; Zhang, Jian; Jiang, Zongyong

2016-06-28

Probiotics are considered as the best effective alternatives to antibiotics. The aim of this study was to characterize the probiotic potential of lactobacilli for use in swine farming by using in vitro evaluation methods. A total of 106 lactic acid bacterial isolates, originating from porcine feces, were first screened for the capacity to survive stresses considered important for putative probiotic strains. Sixteen isolates showed notable acid and bile resistance, antibacterial activity, and adherence to intestinal porcine epithelial cells (IPEC-1). One isolate, LR1, identified as Lactobacillus reuteri, was selected for extensive study of its probiotic and functional properties in IPEC-1 cell models. L. reuteri LR1 exhibited good adhesion to IPEC-1 cells and could inhibit the adhesion of enterotoxigenic Escherichia coli (ETEC) to IPEC-1 cells. L. reuteri LR1 could also modulate transcript and protein expression of cytokines involved in inflammation in IPEC-1 cells; the Lactobacillus strain inhibited the ETEC-induced expression of proinflammatory transcripts (IL-6 and TNF-α) and protein (IL-6), and increased the level of anti-inflammatory cytokine (IL-10). Measurement of the permeation of FD-4 showed that L. reuteri LR1 could maintain barrier integrity in monolayer IPEC-1 cells exposed to ETEC. Immunolocalization experiments showed L. reuteri LR1 could also prevent ETEC-induced tight junction ZO-1 disruption. Together, these results indicate that L. reuteri LR1 exhibits desirable probiotic properties and could be a potential probiotic for use in swine production.

Nanoparticulated heat-stable (STa) and heat-labile B subunit (LTB) recombinant toxin improves vaccine protection against enterotoxigenic Escherichia coli challenge in mouse.

PubMed

Deng, Guangcun; Zeng, Jin; Jian, Minjie; Liu, Wenmiao; Zhang, Zhong; Liu, Xiaoming; Wang, Yujiong

2013-02-01

Enterotoxigenic Escherichia coli (ETEC) remains a major cause of diarrheic disease in developing areas, for which there is no effective vaccine available. In this study, we genetically engineered a recombinant heat-stable enterotoxin (STa) coupled to the subunit B of heat-labile enterotoxin (LTB). This fusion protein, STa-LTB, possesses a single amino acid substitution at position 14 of STa. Our data demonstrates that the enterotoxicity of STa in STa-LTB was dramatically reduced. A gelatin nanovaccine candidate was prepared using the purified STa-LTB fusion protein characterized with an entrapment efficiency of 84.88 ± 6.37% and smooth spheres size ranges of 80-200 nm. Antigen-specific antibody responses against STa-LTB and STa in the sera and the intestinal mucus respectively were used to test the immunogenicity of the nanovaccine. This vaccine was further screened in mice by its ability to elicit neutralizing antibodies against STa and protect animals from the challenge with ETEC in mice. The STa-LTB nanoparticles delivered demonstrated a capacity to induce significantly higher and long-lasting antibody responses and increased immune protection against ETEC challenge relative to the control STa-LTB vaccine absorbed in conventional aluminum hydrate salt (p < 0.01). These results warrant the further studies of the development of a novel nanoparticulate vaccine as a broad-spectrum vaccine against ETEC infection. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Distribution of Escherichia coli F4 adhesion phenotypes in pigs of 15 Chinese and Western breeds and a White DurocxErhualian intercross.

PubMed

Yan, Xueming; Huang, Xiang; Ren, Jun; Zou, Zhengzhi; Yang, Shujin; Ouyang, Jing; Zeng, Weihong; Yang, Bin; Xiao, Shijun; Huang, Lusheng

2009-08-01

Diarrhoea in newborn and weaned piglets is mainly caused by enterotoxigenic Escherichia coli (ETEC) with fimbriae F4. To investigate the prevalence of resistance to three fimbrial strains, F4ab, F4ac and F4ad, among Chinese indigenous pigs and Western commercial pigs introduced into China, we determined the ETEC F4 adhesion phenotypes in 292 pure-bred piglets from three Western commercial breeds and 12 Chinese indigenous breeds, and a total of 1093 adult pigs in a White DurocxErhualian intercross, by an in vitro microscopic adhesion assay. All the Tibet and Lantang pigs and a majority of the Erhualian and Rongchang pigs were resistant (nonadherent) to ETEC F4 whereas all the Laiwu pigs and most of the Jiangquhai and Tongcheng pigs were susceptible (adhesive) to at least one of the F4 strains. Yushan Black pigs were uniformly resistant to F4ab, and Jinhua pigs were predominantly resistant to F4ac. Susceptible and resistant animals were observed in the other breeds, indicating that diarrhoea caused by ETEC F4 could be prevalent in these breeds. This study confirmed the existence of eight previously reported F4 adhesion patterns, and supported the assumption that the three F4 receptors are encoded by distinct loci. Expression of the weakly adherent phenotype was observed in six pure-bred piglets and 90 adult F(2)/F(3) animals, and the inheritance of this phenotype and its correlation with susceptibility to disease are still not known.

Hydrolysable chestnut tannins for reduction of postweaning diarrhea: Efficacy on an experimental ETEC F4 model.

PubMed

Girard, Marion; Thanner, Sophie; Pradervand, Nicolas; Hu, Dou; Ollagnier, Catherine; Bee, Giuseppe

2018-01-01

An experimental model for postweaning diarrhea with enterotoxigenic Escherichia coli F4 (ETEC F4) was set up in piglets, and the efficacy of 1% chestnut-tannin extract in preventing diarrhea was subsequently assessed. In a first trial (infection model), 32 Swiss Large White piglets (age: 24 days; average BW: 7.8 ± 0.8 kg) were randomly assigned to two experimental groups (infected [INF], noninfected [NINF]). In a subsequent trial, 72 Swiss Large White piglets (age: 26 days; average BW: 7.4 ± 1.5 kg) were blocked by BW and assigned within block to four experimental groups: NINF-CO: not infected and fed a standard control starter diet (CO); INF-CO: infected and fed the CO diet; NINF-TA: not infected and fed the CO diet supplemented with 1% chestnut extract containing 54% of hydrolysable tannins (TA); and INF-TA: infected and fed the TA diet. Both diets (TA and CO) were formulated to be isocaloric and isoproteic and to meet or surpass the nutritional requirements. In both trials, four days after weaning, piglets assigned to the INF group received an oral suspension of ETEC F4. Fecal score, ETEC shedding in feces (only in trial 2), and growth performance traits were measured for the following 14 days post infection. In both trials, more than 50% of the INF piglets developed diarrhea within six days post infection. Tannins reduced (P < 0.05) the average fecal score, the percentage of piglets in diarrhea, and the duration of diarrhea, whereas feed intake and the average daily gain were unaffected.

A single-chain fragment variable recombinant antibody against F5 fimbria of enterotoxigenic Escherichia coli inhibits agglutination of horse red blood cells induced by F5 protein.

PubMed

Bhaskaran, S; Jay, C M; Berghman, L R; Wagner, G G; Waghela, S D

2005-08-01

Bovine colibacillosis caused by enterotoxigenic Escherichia coli (ETEC) is a worldwide problem. Adhesion of ETEC to intestinal cell receptors mediated by the surface protein F5 fimbriae is the initial step in the establishment of colibacillosis. Prevention of ETEC F5(+) adhesion to enterocytes protects newborn calves against collibacillosis. On the enterocytes, the F5 fimbriae bind to a ganglioside that is also found on horse red blood cells. Thus, the presence of F5 fimbriae induces haemagglutination, which is useful as an indicator in a functional assay system. In this study, recombinant anti-F5 scFv antibody fragment produced in E. coli HB2151 reacted with F5 fimbriae in ELISA and Western immunoblot, and prevented haemagglutination induced by the binding of the F5 fimbriae to its natural host receptors on horse red blood cells. Given the ease with which recombinant antibodies can be mass-produced, the presently described scFv may hold promise as a prophylactic agent for colibacillosis.

Immunogenicity of nuclear-encoded LTB:ST fusion protein from Escherichia coli expressed in tobacco plants.

PubMed

Rosales-Mendoza, Sergio; Soria-Guerra, Ruth E; Moreno-Fierros, Leticia; Govea-Alonso, Dania O; Herrera-Díaz, Areli; Korban, Schuyler S; Alpuche-Solís, Ángel G

2011-06-01

Enterotoxigenic Escherichia coli (ETEC) is one of the main causative agents of diarrhea in infants and for travelers. Inclusion of a heat-stable (ST) toxin into vaccine formulations is mandatory as most ETEC strains can produce both heat-labile (LT) and ST enterotoxins. In this study, a genetic fusion gene encoding for an LTB:ST protein has been constructed and transferred into tobacco via Agrobacterium tumefaciens-mediated transformation. Transgenic tobacco plants carrying the LTB:ST gene are then subjected to GM1-ELISA revealing that the LTB:ST has assembled into pentamers and displays antigenic determinants from both LTB and ST. Protein accumulation of up to 0.05% total soluble protein is detected. Subsequently, mucosal and systemic humoral responses are elicited in mice orally dosed with transgenic tobacco leaves. This has suggested that the plant-derived LTB:ST is immunogenic via the oral route. These findings are critical for the development of a plant-based vaccine capable of eliciting broader protection against ETEC and targeting both LTB and ST. Features of this platform in comparison to transplastomic approaches are discussed.

High Frequency of Diarrheagenic Escherichia coli in HIV-Infected Patients and Patients with Thalassemia in Kerman, Iran.

PubMed

Alizade, Hesam; Sharifi, Hamid; Naderi, Zahedeh; Ghanbarpour, Reza; Bamorovat, Mehdi; Aflatoonian, Mohammad Reza

This study was conducted on patients with thalassemia and HIV-infected patients to determine the frequency of diarrheagenic Escherichia coli in Kerman, Iran. We analyzed 68 and 49 E coli isolates isolated from healthy fecal samples of patients with thalassemia and HIV-infected patients, respectively. The E coli isolates were studied using a multiplex polymerase chain reaction to identify the enterotoxigenic E coli (ETEC), enterohemorrhagic E coli (EHEC), and enteropathogenic E coli (EPEC) groups. Statistical analysis was carried out to determine the correlation of diarrheagenic E coli between HIV-infected patients and patients with thalassemia using Stata 11.2 software. The frequency of having at least 1 diarrheagenic E coli was more common in patients with thalassemia (67.64%) than in HIV-infected patients (57.14%; P = .25), including ETEC (67.64% versus 57.14%), EHEC (33.82% versus 26.53%), and EPEC (19.11% versus 16.32%). The results of this study indicate that ETEC, EHEC, and EPEC pathotypes are widespread among diarrheagenic E coli isolates in patients with thalassemia and HIV-infected patients.

Both flagella and F4 fimbriae from F4ac+ enterotoxigenic Escherichia coli contribute to attachment to IPEC-J2 cells in vitro.

PubMed

Zhou, Mingxu; Duan, Qiangde; Zhu, Xiaofang; Guo, Zhiyan; Li, Yinchau; Hardwidge, Philip R; Zhu, Guoqiang

2013-05-13

The role of flagella in the pathogenesis of F4ac+ Enterotoxigenic Escherichia coli (ETEC) mediated neonatal and post-weaning diarrhea (PWD) is not currently understood. We targeted the reference C83902 ETEC strain (O8:H19:F4ac+ LT+ STa+ STb+), to construct isogenic mutants in the fliC (encoding the major flagellin protein), motA (encoding the flagella motor), and faeG (encoding the major subunit of F4 fimbriae) genes. Both the ΔfliC and ΔfaeG mutants had a reduced ability to adhere to porcine intestinal epithelial IPEC-J2 cells. F4 fimbriae expression was significantly down-regulated after deleting fliC, which revealed that co-regulation exists between flagella and F4 fimbriae. However, there was no difference in adhesion between the ΔmotA mutant and its parent strain. These data demonstrate that both flagella and F4 fimbriae are required for efficient F4ac+ ETEC adhesion in vitro.

Piglet colibacillosis diagnosis based on multiplex polymerase chain reaction and immunohistochemistry of paraffin-embedded tissues

PubMed Central

de Andrade, Caroline P.; Machado, Verônica S. L.; Bianchi, Matheus V.; Rolim, Veronica M.; Cruz, Raquel A. S.; Driemeier, David

2018-01-01

Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in pigs, referred to as colibacillosis. The aim of this study was to optimize multiplex polymerase chain reaction (PCR) and immunohistochemistry (IHC) analyses of paraffin-embedded material to detect pathogenic E. coli strains causing colibacillosis in pigs. Multiplex PCR was optimized for fimbriae (F18, F4, F6, F5, and F41) and toxins (types A and B heat-stable toxins [STaP and STb], heat-labile toxin [LT], and type 2 Shiga toxin [STx2e]), and IHC was optimized for an anti-E. coli polyclonal antibody. Samples (132) from pigs received between 2006 and 2014 with clinical and histopathological diagnoses of colibacillosis were analyzed. E. coli was detected by IHC in 78.7%, and at least one virulence factor gene was detected in 71.2%. Pathogenic strains of ETEC with at least one fimbria and one toxin were detected in 40% of the samples in multiplex PCR. The most frequent virulence types were F18-STaP (7.5%), F18-STaP-STb (5.7%), and F4-STaP (3.8%). A statistically significant association was noted between virulence factors F4, F18, STaP, and STb and positive immunostaining results. Colibacillosis diagnosis through multiplex PCR and IHC of paraffin-embedded tissues is a practical approach, as samples can be fixed and stored for long periods before analysis. PMID:28693311

Seasonality of diarrheagenic Escherichia coli pathotypes in the US students acquiring diarrhea in Mexico.

PubMed

Paredes-Paredes, Mercedes; Okhuysen, Pablo C; Flores, Jose; Mohamed, Jamal A; Padda, Ranjit S; Gonzalez-Estrada, Alexei; Haley, Clinton A; Carlin, Lily G; Nair, Parvathy; DuPont, Herbert L

2011-01-01

Up to 60% of the US visitors to Mexico develop travelers' diarrhea (TD). In Mexico, rates of diarrhea have been associated with the rainy season and increase in ambient temperature. However, the seasonality of the various diarrheagenic Escherichia coli pathotypes in travelers has not been well described. A study was undertaken to determine if ambient temperature and rainfall have an impact on the acquisition of TD due to different diarrheagenic E coli pathotypes in Mexico. We conducted a cohort study of the US adult students traveling to Cuernavaca, Mexico, who were followed during their stay and provided a stool sample with the onset of TD. The presence of E coli was analyzed by a direct fecal multiplex polymerase chain reaction for common E coli pathotypes including enterotoxigenic, enteropathogenic, enteroinvasive, shiga toxin-producing, and enteroaggregative E coli (ETEC, EPEC, EIEC, STEC, and EAEC respectively). The presence of pathotypes was correlated with daily rainfall, average, maximum, and minimum temperatures. A total of 515 adults were enrolled from January 2006 to February 2007. The weekly attack rate of TD for newly arrived travelers was lower in the winter months (range 6.8%-16.3%) than in summer months (range 11.5%-25%; p = 0.05). The rate of ETEC infection increased by 7% for each degree centigrade increase in weekly ambient temperature (p = 0.003). In contrast, EPEC and EAEC were identified in similar proportions during the winter and summer seasons. Temperature variations in central Mexico influenced the rate of ETEC but not EAEC-associated diarrhea in the US visitors. This epidemiological finding could influence seasonal recommendations for the use of ETEC vaccines in Mexico. © 2011 International Society of Travel Medicine.

A proteinaceous fraction of wheat bran may interfere in the attachment of enterotoxigenic E. coli K88 (F4+) to porcine epithelial cells.

PubMed

González-Ortiz, Gemma; Bronsoms, Sílvia; Quarles Van Ufford, H C; Halkes, S Bart A; Virkola, Ritva; Liskamp, Rob M J; Beukelman, Cees J; Pieters, Roland J; Pérez, José Francisco; Martín-Orúe, Susana María

2014-01-01

Wheat bran (WB) from Triticum aestivum has many beneficial effects on human health. To the best of our knowledge, very little has been published about its ability to prevent pathogenic bacterial adhesion in the intestine. Here, a WB extract was fractionated using different strategies, and the obtained fractions were tested in different in vitro methodologies to evaluate their interference in the attachment of enterotoxigenic Escherichia coli (ETEC) K88 to intestinal porcine epithelial cells (IPEC-J2) with the aim of identifying the putative anti-adhesive molecules. It was found that a proteinaceous compound in the >300-kDa fraction mediates the recognition of ETEC K88 to IPEC-J2. Further fractionation of the >300-kDa sample by size-exclusion chromatography showed several proteins below 90 kDa, suggesting that the target protein belongs to a high-molecular-weight (MW) multi-component protein complex. The identification of some relevant excised bands was performed by mass spectrometry (MS) and mostly revealed the presence of various protease inhibitors (PIs) of low MW: Serpin-Z2B, Class II chitinase, endogenous alpha-amylase/subtilisin inhibitor and alpha-amylase/trypsin inhibitor CM3. Furthermore, an incubation of the WB extract with ETEC K88 allowed for the identification of a 7S storage protein globulin of wheat, Globulin 3 of 66 kDa, which may be one of the most firmly attached WB proteins to ETEC K88 cells. Further studies should be performed to gain an understanding of the molecular recognition of the blocking process that takes place. All gathered information can eventually pave the way for the development of novel anti-adhesion therapeutic agents to prevent bacterial pathogenesis.

Enterotoxigenic Escherichia coli heat-stable toxin and heat-labile toxin toxoid fusion 3xSTaN12S-dmLT induces neutralizing anti-STa antibodies in subcutaneously immunized mice.

PubMed

Nandre, Rahul; Ruan, Xiaosai; Duan, Qiangde; Zhang, Weiping

2016-11-02

Enterotoxigenic Escherichia coli (ETEC) bacteria producing heat-stable toxin (STa) and/or heat-labile toxin (LT) are among top causes of children's diarrhea and travelers' diarrhea. Currently no vaccines are available for ETEC associated diarrhea. A major challenge in developing ETEC vaccines is the inability to stimulate protective antibodies against the key STa toxin which is potently toxic and also poorly immunogenic. A recent study suggested toxoid fusion 3xSTa N12S -dmLT, which consists of a monomer LT toxoid (LT R192G/L211A ) and three copies of STa toxoid STa N12S , may represent an optimal immunogen inducing neutralizing antibodies against STa toxin [IAI 2014, 82(5):1823-32]. In this study, we immunized mice with this fusion protein following a different parenteral route and using different adjuvants to further characterize immunogenicity of this toxoid fusion. Data from this study showed that 3xSTa N12S -dmLT toxoid fusion induced neutralizing anti-STa antibodies in the mice following subcutaneous immunization, as effectively as in the mice under intraperitoneal route. Data also indicated that double mutant LT (dmLT) can be an effective adjuvant for this toxoid fusion in mice subcutaneous immunization. Results from this study affirmed that toxoid fusion 3xSTa N12S -dmLT induces neutralizing antibodies against STa toxin, suggesting this toxoid fusion is potentially a promising immunogen for ETEC vaccine development. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells

PubMed Central

Liu, Hao-Yu; Roos, Stefan; Jonsson, Hans; Ahl, David; Dicksved, Johan; Lindberg, Jan Erik; Lundh, Torbjörn

2015-01-01

Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic, Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on cytoprotective HSP expression and gut barrier function, were investigated in a porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells polarized on a permeable filter exhibited villus-like cell phenotype with development of apical microvilli. Western blot analysis detected HSP expression in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG did not. For HSP72, only the supernatant of L. reuteri induced the expression, which was comparable to the heat shock treatment, which indicated that HSP72 expression was more stimulus specific. The protective effect of lactobacilli was further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC) challenge. ETEC caused intestinal barrier destruction, as reflected by loss of cell–cell contact, reduced IPEC-J2 cell viability and transepithelial electrical resistance, and disruption of tight junction protein zonula occludens-1. In contrast, the L. reuteri treatment substantially counteracted these detrimental effects and preserved the barrier function. L. johnsonii and LGG also achieved barrier protection, partly by directly inhibiting ETEC attachment. Together, the results indicate that specific strains of Lactobacillus can enhance gut barrier function through cytoprotective HSP induction and fortify the cell protection against ETEC challenge through tight junction protein modulation and direct interaction with pathogens. PMID:25847917

2007 Nissan Altima-2351 Hybrid Electric Vehicle Battery Test Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tyler Gray; Chester Motloch; James Francfort

2010-01-01

The U.S. Department of Energy's (DOE) Advanced Vehicle Testing Activity (AVTA) conducts several different types of tests on hybrid electric vehicles (HEVs), including testing the HEV batteries when both the vehicles and batteries are new, and at the conclusion of 160,000 miles of on-road accelerated testing. This report documents the battery testing performed and the battery testing results for the 2007 Nissan Altima HEV, number 2351 (VIN 1N4CL21E87C172351). The battery testing was performed by the Electric Transportation Engineering Corporation (eTec). The Idaho National Laboratory and eTec conduct the AVTA for DOE’s Vehicle Technologies Program.

Site Environmental Report for Calendar Year 2003 DOE Operations at The Boeing Company, Rocketdyne Propulsion & Power

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ning; Rutherford, Phil; Samuels, Sandy

2004-09-30

This Annual Site Environmental Report (ASER) for 2003 describes the environmental conditions related to work performed for the Department of Energy (DOE) at Area IV of Boeing Rocketdyne’s Santa Susana Field Laboratory (SSFL). In the past, the Energy Technology Engineering Center (ETEC), a government-owned, company-operated test facility, was located in Area IV. The operations at ETEC included development, fabrication, and disassembly of nuclear reactors, reactor fuel, and other radioactive materials. Other activities at ETEC involved the operation of large-scale liquid metal facilities that were used for testing liquid metal fast breeder components. All nuclear work was terminated in 1988; allmore » subsequent radiological work has been directed toward decontamination and decommissioning (D&D) of the former nuclear facilities and their associated sites. Closure of the liquid metal test facilities began in 1996. Results of the radiological monitoring program for the calendar year 2003 continue to indicate that there are no significant releases of radioactive material from Area IV of SSFL. All potential exposure pathways are sampled and/or monitored, including air, soil, surface water, groundwater, direct radiation, transfer of property (land, structures, waste), and recycling.« less

Clostridium difficile carbohydrates: glucan in spores, PSII common antigen in cells, immunogenicity of PSII in swine and synthesis of a dual C. difficile-ETEC conjugate vaccine.

PubMed

Bertolo, Lisa; Boncheff, Alexander G; Ma, Zuchao; Chen, Yu-Han; Wakeford, Terra; Friendship, Robert M; Rosseau, Joyce; Weese, J Scott; Chu, Michele; Mallozzi, Michael; Vedantam, Gayatri; Monteiro, Mario A

2012-06-01

Clostridium difficile is responsible for severe diarrhea in humans that may cause death. Spores are the infectious form of C. difficile, which germinate into toxin-producing vegetative cells in response to bile acids. Recently, we discovered that C. difficile cells possess three complex polysaccharides (PSs), named PSI, PSII, and PSIII, in which PSI was only associated with a hypervirulent ribotype 027 strain, PSII was hypothesized to be a common antigen, and PSIII was a water-insoluble polymer. Here, we show that (i) C. difficile spores contain, at least in part, a D-glucan, (ii) PSI is not a ribotype 027-unique antigen, (iii) common antigen PSII may in part be present as a low molecular weight lipoteichoic acid, (iv) selective hydrolysis of PSII yields single PSII repeat units, (v) the glycosyl diester-phosphate linkage affords high flexibility to PSII, and (vi) that PSII is immunogenic in sows. Also, with the intent of creating a dual anti-diarrheal vaccine against C. difficile and enterotoxin Escherichia coli (ETEC) infections in humans, we describe the conjugation of PSII to the ETEC-associated LTB enterotoxin. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical Characteristics and Etiology of Travelers' Diarrhea among Korean Travelers Visiting South-East Asia

PubMed Central

Ahn, Ji Yong; Chang, Kyu-Jin; You, Myung Hwan; Chai, Jin Sung; Kang, Young A; Kim, Seong-Han; Jeoung, Hyesook; Cheon, Doosung; Jeoung, Ahyong; Choi, Eun Suk

2011-01-01

The morbidity of travelers' diarrhea (TD) is still high. This study examined the incidence of common pathogens and characteristics of TD among Korean travelers who visited South-East Asian countries. We performed a prospective study involving 479 Korean travelers with diarrheal disease from February 2009 to April 2009 and stool samples were examined and questionnaire surveys were done after arrival. Enterotoxigenic Escherichia coli (ETEC) was found in 36.0% of TD cases, as were the following: Enteroaggregative Escherichia coli (EAEC) in 27.0%, Vibrio parahaemolyticus in 13.1%, and Norovirus in 11.5%. The detected rate of classic TD was higher in men (P = 0.007), in patients who had a shorter duration trip (P = 0.023) and in patients who drank more than 1 liter of water per day (P = 0.037). Positive stool culture rates were higher in men (P = 0.005), in hospitalized patients (P = 0.013). and in those who consumed impure water or raw foods (P = 0.033). A higher severity of disease corresponded to a significantly higher culture positivity rate (P = 0.029). We should consider the possibility of other pathogens in addition to ETEC in patients with TD who visit South-East Asia. Travelers need to educate about risk factors associated with TD. PMID:21286009

Clinical characteristics and etiology of travelers' diarrhea among Korean travelers visiting South-East Asia.

PubMed

Ahn, Ji Yong; Chung, Jin-Won; Chang, Kyu-Jin; You, Myung Hwan; Chai, Jin Sung; Kang, Young A; Kim, Seong-Han; Jeoung, Hyesook; Cheon, Doosung; Jeoung, Ahyong; Choi, Eun Suk

2011-02-01

The morbidity of travelers' diarrhea (TD) is still high. This study examined the incidence of common pathogens and characteristics of TD among Korean travelers who visited South-East Asian countries. We performed a prospective study involving 479 Korean travelers with diarrheal disease from February 2009 to April 2009 and stool samples were examined and questionnaire surveys were done after arrival. Enterotoxigenic Escherichia coli (ETEC) was found in 36.0% of TD cases, as were the following: Enteroaggregative Escherichia coli (EAEC) in 27.0%, Vibrio parahaemolyticus in 13.1%, and Norovirus in 11.5%. The detected rate of classic TD was higher in men (P = 0.007), in patients who had a shorter duration trip (P = 0.023) and in patients who drank more than 1 liter of water per day (P = 0.037). Positive stool culture rates were higher in men (P = 0.005), in hospitalized patients (P = 0.013). and in those who consumed impure water or raw foods (P = 0.033). A higher severity of disease corresponded to a significantly higher culture positivity rate (P = 0.029). We should consider the possibility of other pathogens in addition to ETEC in patients with TD who visit South-East Asia. Travelers need to educate about risk factors associated with TD.

Preliminary X-ray diffraction analysis of CfaA, a molecular chaperone essential for the assembly of CFA/I fimbriae of human enterotoxigenic Escherichia coli.

PubMed

Bao, Rui; Esser, Lothar; Poole, Steven; McVeigh, Annette; Chen, Yu Xing; Savarino, Stephen J; Xia, Di

2014-02-01

Understanding of pilus bioassembly in Gram-negative bacteria stems mainly from studies of P pili and type 1 fimbriae of uropathogenic Escherichia coli, which are mediated by the classic chaperone-usher pathway (CUP). However, CFA/I fimbriae, a class 5 fimbria and intestinal colonization factor for enterotoxigenic E. coli (ETEC), are proposed to assemble via the alternate chaperone pathway (ACP). Both CUP and ACP fimbrial bioassembly pathways require the function of a periplasmic chaperone, but their corresponding proteins share very low similarity in primary sequence. Here, the crystallization of the CFA/I periplasmic chaperone CfaA by the hanging-drop vapor-diffusion method is reported. X-ray diffraction data sets were collected from a native CfaA crystal to 2 Å resolution and to 1.8 and 2.8 Å resolution, respectively, from a lead and a platinum derivative. These crystals displayed the symmetry of space group C2, with unit-cell parameters a = 103.6, b = 28.68, c = 90.60 Å, β = 119.7°. Initial phases were derived from multiple isomorphous replacement with anomalous scattering experiments using the data from the platinum and lead derivatives. This resulted in an interpretable electron-density map showing one CfaA molecule in an asymmetric unit. Sequence assignments were aided by anomalous signals from the heavy-atom derivatives. Refinement of the atomic model of CfaA is ongoing, which is expected to further understanding of the essential aspects and allowable variations in tertiary structure of the greater family of chaperones involved in chaperone-usher mediated bioassembly.

Molecules produced by probiotics prevent enteric colibacillosis in pigs.

PubMed

Nordeste, Ricardo; Tessema, Akalate; Sharma, Sapana; Kovač, Zlatko; Wang, Chuan; Morales, Rocio; Griffiths, Mansel William

2017-11-15

With the advent of antimicrobial resistance in animal pathogens, novel methods to combat infectious diseases are being sought. Among these, probiotics have been proposed as a means of promoting animal health but problems with their use has been reported. Research has demonstrated that bioactive molecules produced during the growth of certain probiotics interfere with bacterial cell-to-cell communication, which consequently results in an attenuation of virulence in a number of pathogens, including E. coli. The objective of this study was to determine the efficacy of the bioactive molecules, termed proteobiotics, produced by Lactobacillus acidophilus in preventing enterotoxigenic E, coli (ETEC) infection in pigs, which is the etiological agent for enteric colibacillosis, a common disease of nursing and young pigs. To achieve this, piglets were fed a preparation of the bioactive at four levels: 0, 0.5×, 1.0× and 2.0× for 7 days prior to challenge with E. coli K88. There were 36 pigs (18 gilts and 18 barrows) per treatment, resulting in 144 piglets in total for the study. Each pen had 6 piglets (3 gilts and 3 barrows). Only piglets with no physical abnormality or conditions were used in the trial and intact male piglets and ridglings were excluded. The bioactive continued to be fed to the pigs post-challenge. Based of fecal and demeanour scores, pigs fed the low and high dose of the proteobiotic were significanlty less likely to show symptoms of illness than pigs fed no bioactive. While not being significant, the weight gain of pigs given the proteobiotics was improved. At day 4 following challenge, almost 50% of piglets that did not receive the proteobiotic were shedding ETEC in their feces, compared with about 15% of animals receiving the supplement. There was also an indication that the proteobiotics reduced colonization of the ileum by E. coli K88 and improved gut health. This study indicates that the bioactive molecules produced by L. acidophilus reduces incidence of enteric colibacillosis in pigs and their use on farms would help to reduce antibiotic use.

Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice.

PubMed

Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Jung, Myunghwan; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

2012-05-01

A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC. Copyright © 2012 Elsevier B.V. All rights reserved.

High number of diarrhoeal co-infections in travellers to Benin, West Africa.

PubMed

Lääveri, Tinja; Pakkanen, Sari H; Antikainen, Jenni; Riutta, Jukka; Mero, Sointu; Kirveskari, Juha; Kantele, Anu

2014-02-12

Travellers' diarrhoea (TD) is the most frequent health problem among travellers to the tropics. Using routine techniques, the aetiology mostly remains unresolved, whereas modern molecular methods enable reducing the number of equivocal cases considerably. While many studies address the aetiology of TD in Asian, Central American and North African tourist resorts, only few focus on Western Africa. Stool samples from 45 travellers travelling in Benin, West Africa, were analyzed by a new multiplex qPCR assay for Salmonella, Yersinia, Campylobacter, Vibrio cholerae, Shigella or enteroinvasive (EIEC), enterohaemorrhagic (EHEC), enterotoxigenic (ETEC), enteroaggregative (EAEC), and enteropathogenic Escherichia coli (EPEC). All 18 pre-travel samples proved negative for bacterial pathogens. Of the 39/45 (87%) travellers having had TD, EPEC was detected in post-travel samples in 30 (77%) cases, EAEC in 23 (59%), ETEC in 22 (56%), Shigella or EIEC in 7 (18%), EHEC in two (5%), and Salmonella in one (3%). In 31(79%) of the TD cases two or more bacterial pathogens were identified. Two (8%) samples remained negative: both patients had taken antimicrobials for TD. EPEC, EAEC and ETEC were the most common findings. 79% of the cases had a co-infection. As modern diagnostics reveals in most patients a multitude of pathogens, the role of each pathogen should be re-evaluated.

High number of diarrhoeal co-infections in travellers to Benin, West Africa

PubMed Central

2014-01-01

Background Travellers’ diarrhoea (TD) is the most frequent health problem among travellers to the tropics. Using routine techniques, the aetiology mostly remains unresolved, whereas modern molecular methods enable reducing the number of equivocal cases considerably. While many studies address the aetiology of TD in Asian, Central American and North African tourist resorts, only few focus on Western Africa. Methods Stool samples from 45 travellers travelling in Benin, West Africa, were analyzed by a new multiplex qPCR assay for Salmonella, Yersinia, Campylobacter, Vibrio cholerae, Shigella or enteroinvasive (EIEC), enterohaemorrhagic (EHEC), enterotoxigenic (ETEC), enteroaggregative (EAEC), and enteropathogenic Escherichia coli (EPEC). Results All 18 pre-travel samples proved negative for bacterial pathogens. Of the 39/45 (87%) travellers having had TD, EPEC was detected in post-travel samples in 30 (77%) cases, EAEC in 23 (59%), ETEC in 22 (56%), Shigella or EIEC in 7 (18%), EHEC in two (5%), and Salmonella in one (3%). In 31(79%) of the TD cases two or more bacterial pathogens were identified. Two (8%) samples remained negative: both patients had taken antimicrobials for TD. Conclusions EPEC, EAEC and ETEC were the most common findings. 79% of the cases had a co-infection. As modern diagnostics reveals in most patients a multitude of pathogens, the role of each pathogen should be re-evaluated. PMID:24521079

Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells.

PubMed

Liu, Hao-Yu; Roos, Stefan; Jonsson, Hans; Ahl, David; Dicksved, Johan; Lindberg, Jan Erik; Lundh, Torbjörn

2015-04-01

Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic, Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on cytoprotective HSP expression and gut barrier function, were investigated in a porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells polarized on a permeable filter exhibited villus-like cell phenotype with development of apical microvilli. Western blot analysis detected HSP expression in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG did not. For HSP72, only the supernatant of L. reuteri induced the expression, which was comparable to the heat shock treatment, which indicated that HSP72 expression was more stimulus specific. The protective effect of lactobacilli was further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC) challenge. ETEC caused intestinal barrier destruction, as reflected by loss of cell-cell contact, reduced IPEC-J2 cell viability and transepithelial electrical resistance, and disruption of tight junction protein zonula occludens-1. In contrast, the L. reuteri treatment substantially counteracted these detrimental effects and preserved the barrier function. L. johnsonii and LGG also achieved barrier protection, partly by directly inhibiting ETEC attachment. Together, the results indicate that specific strains of Lactobacillus can enhance gut barrier function through cytoprotective HSP induction and fortify the cell protection against ETEC challenge through tight junction protein modulation and direct interaction with pathogens. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study.

PubMed

Olivares, Marta; Benítez-Páez, Alfonso; de Palma, Giada; Capilla, Amalia; Nova, Esther; Castillejo, Gemma; Varea, Vicente; Marcos, Ascensión; Garrote, José Antonio; Polanco, Isabel; Donat, Ester; Ribes-Koninckx, Carmen; Calvo, Carmen; Ortigosa, Luis; Palau, Francesc; Sanz, Yolanda

2018-04-19

Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.

Detection of diarrheagenic Escherichia coli strains isolated from dogs and cats in Brazil.

PubMed

Puño-Sarmiento, Juan; Medeiros, Leonardo; Chiconi, Carolina; Martins, Fernando; Pelayo, Jacinta; Rocha, Sérgio; Blanco, Jorge; Blanco, Miguel; Zanutto, Marcelo; Kobayashi, Renata; Nakazato, Gerson

2013-10-25

Escherichia coli are gut microbiota bacteria that can cause disease in some humans and other animals, including dogs and cats that humans often keep as pets. Diarrheagenic E. coli (DEC) strains are classified into six categories: enteropathogenic (EPEC), enterotoxigenic (ETEC), Shiga toxin-producing (STEC), enteroinvasive (EIEC), enteroaggregative (EAEC), and diffuse-adhering E. coli (DAEC). In this study 144 and 163 E. coli colonies were isolated from the fecal samples of 50 dogs and 50 cats, respectively, with and without diarrhea from a Veterinary Hospital (clinical isolates). The virulence factors were determined using multiplex Polymerase Chain Reaction. Adherence assays, antibacterial susceptibility and serotyping (somatic or flagellar antigens) were performed on DEC isolates. We found 25 (17.4%) and 4 (2.5%) DEC strains isolated from dogs and cats, respectively. Only the EPEC and EAEC pathotypes were found in both animals. Meanwhile, genes from other pathotypes (STEC, EIEC, and ETEC) were not found in these clinical isolates. All of the DEC strains showed mannose-resistant adherence to HEp-2 and HeLa cells, and aggregative adherence was predominant in these isolates. Multiresistant strains to antimicrobials were found in most DEC strains including usual and unusual antimicrobials in veterinary practices. The serotypes of these DEC isolates were variable. The ONT serotype was predominant in these isolates. Some serotypes found in our study were described to human DEC. Here, we demonstrate that pets carry virulent DEC genes, which are mainly strains of EPECs and EAECs. The presence of these virulence factors in isolates from animals without diarrhea suggests that pets can act as a reservoir for human infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Behavior of non-O157 Shiga toxin-producing Escherichia coli, enteroinvasive E. coli, enteropathogenic E. coli, and enterotoxigenic E. coli strains on alfalfa sprouts.

PubMed

Gómez-Aldapa, Carlos A; Rangel-Vargas, Esmeralda; Torres-Vitela, M Del Refugio; Villarruel-López, Angélica; Castro-Rosas, Javier

2013-08-01

Data about the behavior of non-O157 Shiga toxin-producing Escherichia coli (non-O157 STEC), enteroinvasive E. coli (EIEC), enterotoxigenic E. coli (ETEC), and enteropathogenic E. coli (EPEC) on seeds and alfalfa sprouts are not available. The behavior of STEC, EIEC, ETEC, and EPEC was determined during germination and sprouting of alfalfa seeds at 20 ± 2°C and 30 ± 2°C and on alfalfa sprouts at 3 ± 2°C. When alfalfa seeds were inoculated with STEC, EIEC, ETEC, or EPEC strains, all these diarrheagenic E. coli pathotypes (DEPs) grew during germination and sprouting of seeds, reaching counts of approximately 5 and 6 log CFU/g after 1 day at 20 ± 2°C and 30 ± 2°C, respectively. However, when the sprouts were inoculated after 1 day of seed germination and stored at 20 ± 2°C or 30 ± 2°C, no growth was observed for any DEP during sprouting at 20 ± 2°C or 30 ± 2°C for 9 days. Refrigeration reduced significantly (P < 0.0.5) the number of viable DEPs on sprouts after 20 days in storage; nevertheless, these decreases have no practical significance for the safety of the sprouts.

Variation in 12 porcine genes involved in the carbohydrate moiety assembly of glycosphingolipids does not account for differential binding of F4 Escherichia coli and their fimbriae.

PubMed

Goetstouwers, Tiphanie; Van Poucke, Mario; Coddens, Annelies; Nguyen, Van Ut; Melkebeek, Vesna; Deforce, Dieter; Cox, Eric; Peelman, Luc J

2014-10-03

Glycosphingolipids (GSLs) are important membrane components composed of a carbohydrate structure attached to a hydrophobic ceramide. They can serve as specific membrane receptors for microbes and microbial products, such as F4 Escherichia coli (F4 ETEC) and isolated F4 fimbriae. The aim of this study was to investigate the hypothesis that variation in genes involved in the assembly of the F4 binding carbohydrate moiety of GSLs (i.e. ARSA, B4GALT6, GAL3ST1, GALC, GBA, GLA, GLB1, GLB1L, NEU1, NEU2, UGCG, UGT8) could account for differential binding of F4 ETEC and their fimbriae. RT-PCR could not reveal any differential expression of the 12 genes in the jejunum of F4 receptor-positive (F4R(+)) and F4 receptor-negative (F4R(-)) pigs. Sequencing the complete open reading frame of the 11 expressed genes (NEU2 was not expressed) identified 72 mutations. Although some of them might have a structural effect, none of them could be associated with a F4R phenotype. We conclude that no regulatory or structural variation in any of the investigated genes is responsible for the genetic susceptibility of pigs towards F4 ETEC.

F4-related mutation and expression analysis of the aminopeptidase N gene in pigs.

PubMed

Goetstouwers, T; Van Poucke, M; Nguyen, V U; Melkebeek, V; Coddens, A; Deforce, D; Cox, E; Peelman, L J

2014-05-01

Intestinal infections with F4 enterotoxigenic Escherichia coli (ETEC) are worldwide an important cause of diarrhea in neonatal and recently weaned pigs. Adherence of F4 ETEC to the small intestine by binding to specific receptors is mediated by F4 fimbriae. Porcine aminopeptidase N (ANPEP) was recently identified as a new F4 receptor. In this study, 7 coding mutations and 1 mutation in the 3' untranslated region (3' UTR)were identified in ANPEP by reverse transcriptase (RT-) PCR and sequencing using 3 F4 receptor-positive (F4R+) and 2 F4 receptor-negative (F4R-) pigs, which were F4 phenotyped based on the MUC4 TaqMan, oral immunization, and the in vitro villous adhesion assay. Three potential differential mutations (g.2615C > T, g.8214A > G, and g.16875C > G) identified by comparative analysis between the 3 F4R+ and 2 F4R- pigs were genotyped in 41 additional F4 phenotyped pigs. However, none of these 3 mutations could be associated with F4 ETEC susceptibility. In addition, the RT-PCR experiments did not reveal any differential expression or alternative splicing in the small intestine of F4R+ and F4R- pigs. In conclusion, we hypothesize that the difference in F4 binding to ANPEP is due to modifications in its carbohydrate moieties.

Effect of feed supplementation with live yeast on the intestinal transcriptome profile of weaning pigs orally challenged with Escherichia coli F4.

PubMed

Trevisi, P; Latorre, R; Priori, D; Luise, D; Archetti, I; Mazzoni, M; D'Inca, R; Bosi, P

2017-01-01

The ability of live yeasts to modulate pig intestinal cell signals in response to infection with Escherichia coli F4ac (ETEC) has not been studied in-depth. The aim of this trial was to evaluate the effect of Saccharomyces cerevisiae CNCM I-4407 (Sc), supplied at different times, on the transcriptome profile of the jejunal mucosa of pigs 24 h after infection with ETEC. In total, 20 piglets selected to be ETEC-susceptible were weaned at 24 days of age (day 0) and allotted by litter to one of following groups: control (CO), CO+colistin (AB), CO+5×1010 colony-forming unit (CFU) Sc/kg feed, from day 0 (PR) and CO+5×1010 CFU Sc/kg feed from day 7 (CM). On day 7, the pigs were orally challenged with ETEC and were slaughtered 24 h later after blood sampling for haptoglobin (Hp) and C-reactive protein (CRP) determination. The jejunal mucosa was sampled (1) for morphometry; (2) for quantification of proliferation, apoptosis and zonula occludens (ZO-1); (3) to carry out the microarray analysis. A functional analysis was carried out using Gene Set Enrichment Analysis. The normalized enrichment score (NES) was calculated for each gene set, and statistical significance was defined when the False Discovery Rate % was <25 and P-values of NES were <0.05. The blood concentration of CRP and Hp, and the score for ZO-1 integrity on the jejunal villi did not differ between groups. The intestinal crypts were deeper in the AB (P=0.05) and the yeast groups (P<0.05) than in the CO group. Antibiotic treatment increased the number of mitotic cells in intestinal villi as compared with the control group (P<0.05). The PR group tended to increase the mitotic cells in villi and crypts and tended to reduce the cells in apoptosis as compared with the CM group. The transcriptome profiles of the AB and PR groups were similar. In both groups, the gene sets involved in mitosis and in mitochondria development ranked the highest, whereas in the CO group, the gene sets related to cell junction and anion channels were affected. In the CM group, the gene sets linked to the metabolic process, and transcription ranked the highest; a gene set linked with a negative effect on growth was also affected. In conclusion, the constant supplementation in the feed with the strain of yeast tested was effective in counteracting the detrimental effect of ETEC infection in susceptible pigs limits the early activation of the gene sets related to the impairment of the jejunal mucosa.

Pathogenic Escherichia coli producing Extended-Spectrum β-Lactamases isolated from surface water and wastewater.

PubMed

Franz, Eelco; Veenman, Christiaan; van Hoek, Angela H A M; de Roda Husman, Ana; Blaak, Hetty

2015-09-24

To assess public health risks from environmental exposure to Extended-Spectrum β-Lactamases (ESBL)-producing bacteria, it is necessary to have insight in the proportion of relative harmless commensal variants and potentially pathogenic ones (which may directly cause disease). In the current study, 170 ESBL-producing E. coli from Dutch wastewater (n = 82) and surface water (n = 88) were characterized with respect to ESBL-genotype, phylogenetic group, resistance phenotype and virulence markers associated with enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), extraintesinal E. coli (ExPEC), and Shiga toxin-producing E. coli (STEC). Overall, 17.1% of all ESBL-producing E. coli were suspected pathogenic variants. Suspected ExPECs constituted 8.8% of all ESBL-producing variants and 8.3% were potential gastrointestinal pathogens (4.1% EAEC, 1.8% EPEC, 1.2% EIEC, 1.2% ETEC, no STEC). Suspected pathogens were significantly associated with ESBL-genotype CTX-M-15 (X(2) = 14.7, P < 0.001) and phylogenetic group B2 (X(2) = 23.5, P < 0.001). Finally, 84% of the pathogenic ESBL-producing E. coli isolates were resistant to three or more different classes of antibiotics. In conclusion, this study demonstrates that the aquatic environment is a potential reservoir of E. coli variants that combine ESBL-genes, a high level of multi-drug resistance and virulence factors, and therewith pose a health risk to humans upon exposure.

Characterization of the human gut microbiome during travelers' diarrhea

PubMed Central

Youmans, Bonnie P; Ajami, Nadim J; Jiang, Zhi-Dong; Campbell, Frederick; Wadsworth, W Duncan; Petrosino, Joseph F; DuPont, Herbert L; Highlander, Sarah K

2015-01-01

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel. PMID:25695334

Characterization of the human gut microbiome during travelers' diarrhea.

PubMed

Youmans, Bonnie P; Ajami, Nadim J; Jiang, Zhi-Dong; Campbell, Frederick; Wadsworth, W Duncan; Petrosino, Joseph F; DuPont, Herbert L; Highlander, Sarah K

2015-01-01

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.

Health significance and occurrence of injured bacteria in drinking water

NASA Technical Reports Server (NTRS)

McFeters, G. A.; LeChevallier, M. W.; Singh, A.; Kippin, J. S.

1986-01-01

Enteropathogenic and indicator bacteria become injured in drinking water with exposure to sublethal levels of various biological, chemical and physical factors. One manifestation of this injury is the inability to grow and form colonies on selective media containing surfactants. The resulting underestimation of indicator bacteria can lead to a false estimation of water potability. m-T7 medium was developed specifically for the recovery of injured coliforms (both "total" and fecal) in drinking water. The m-T7 method was used to survey operating drinking water treatment and distribution systems for the presence of injured coliforms that were undetected with currently used media. The mean recovery with m-Endo LES medium was less than 1/100 ml while it ranged between 6 and 68/100ml with m-T7 agar. The majority of samples giving positive results with m-T7 medium yielded no detectable coliforms with m-Endo LES agar. Over 95% of the coliform bacteria in these samples were injured. Laboratory experiments were also done to ascribe the virulence of injured waterborne pathogens. Enteropathogens including Salmonella typhimurium, Yersinia enterocolitica and Shigella spp. required up to 20 times the chlorine levels to produce the same injury in enterotoxigenic Escherichia coli (ETEC) and nonpathogenic coliforms. Similar results were seen with Y. enterocolitica exposed to copper. The recovery of ETEC was followed by delayed enterotoxin production, both in vitro and in the gut of experimental animals. This indicates that injured waterborne enteropathogenic bacteria can be virulent.

Independent risk factors of morbidity in penetrating colon injuries.

PubMed

Girgin, Sadullah; Gedik, Ercan; Uysal, Ersin; Taçyildiz, Ibrahim Halil

2009-05-01

The present study explored the factors effective on colon-related morbidity in patients with penetrating injury of the colon. The medical records of 196 patients were reviewed for variables including age, gender, factor of trauma, time between injury and operation, shock, duration of operation, Penetrating Abdominal Trauma Index (PATI), Injury Severity Score (ISS), site of colon injury, Colon Injury Score, fecal contamination, number of associated intra- and extraabdominal organ injuries, units of transfused blood within the first 24 hours, and type of surgery. In order to determine the independent risk factors, multivariate logistic regression analysis was performed. Gunshot wounds, interval between injury and operation > or =6 hours, shock, duration of the operation > or =6 hours, PATI > or =25, ISS > or =20, Colon Injury Score > or = grade 3, major fecal contamination, number of associated intraabdominal organ injuries >2, number of associated extraabdominal organ injuries >2, multiple blood transfusions, and diversion were significantly associated with morbidity. Multivariate logistic regression analysis showed diversion and transfusion of > or =4 units in the first 24 hours as independent risk factors affecting colon-related morbidity. Diversion and transfusion of > or =4 units in the first 24 hours were determined to be independent risk factors for colon-related morbidity.

DUV mask writer for BEOL 90-nm technology layers

NASA Astrophysics Data System (ADS)

Hong, Dongsung; Krishnan, Prakash; Coburn, Dianna; Jeewakhan, Nazneen; Xie, Shengqi; Broussard, Joshua; Ferguson, Bradley; Green, Kent G.; Buck, Peter; Jackson, Curt A.; Martinez, Larry

2003-12-01

Mask CD resolution and uniformity requirements for back end of line (BEOL) layers for the 90nm Technology Node push the capability of I-line mask writers; yet, do not require the capability offered by more expensive 50KeV ebeam mask writers. This suite of mask layers seems to be a perfect match for the capabilities of the DUV mask writing tools, which offer a lower cost option to the 50KeV platforms. This paper will evaluate both the mask and wafer results from all three platforms of mask writers (50KeV VSB,ETEC Alta 4300TM DUV laser and ETEC Alta 3500TM I-line laser) for a Cypress 90nm node Metal 1 layer, and demonstrate the benefits of the DUV platform with no change to OPC for this layer.

Evaluation of M307 of FUT1 gene as a genetic marker for disease resistance breeding of Sutai pigs.

PubMed

Bao, Wen-Bin; Ye, Lan; Zhu, Jing; Pan, Zhang-Yuan; Zhu, Guo-Qiang; Huang, Xue-Gen; Wu, Sheng-Long

2012-04-01

Alpha (1,2) fucosyltransferase (FUT1) gene has been identified as a candidate gene for controlling the expression of the receptor for ETEC F18. The genetic variations in the position of M307 nucleotide in open reading frame of FUT1 have been proposed as a marker for selecting ETEC F18 resistant pigs. The polymorphisms of M307 in FUT1 of breeding base group for ETEC F18 resistance of Sutai pigs (Duroc × Meishan) was detected and their correlations to some immune indexes, growth and development ability, carcass traits and meat quality were also analyzed, which aimed to investigate feasibility of further breeding for diseases resistance based on M307 of FUT1 for Sutai pigs. After digested by Hin6 I, M307 of FUT1 gene could be divided into three kinds of genotypes, AA, AG, and GG. The frequencies were 0.235, 0.609, and 0.156, respectively. The results indicated that Sutai pigs with the AA genotype in M307 of FUT1 gene not only have relatively strong general disease resistance ability in piglets, but also have higher growth and development ability and stable carcass traits and meat quality. It is entirely feasible to raise the new strains of Sutai pigs resistant to Escherichia coli F18 based on genetic marker of the M307 position in FUT1gene.

Site environmental report for calendar year 2002. DOE operations at the Boeing Company, Rocketdyne Propulsion and Power

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2003-09-30

This Annual Site Environmental Report (ASER) for 2002 describes the environmental conditions related to work performed for the Department of Energy (DOE) at Area IV of Boeing' s Santa Susana Field Laboratory (SSFL)). In the past, the Energy Technology Engineering Center (ETEC), a government-owned, company-operated test facility, was located in Area IV. The operations at ETEC included development, fabrication, and disassembly of nuclear reactors, reactor fuel, and other radioactive materials. Other activities at ETEC involved the operation of large-scale liquid metal facilities that were used for testing liquid metal fast breeder components. All nuclear work was terminated in 1988, and,more » subsequently, all radiological work has been directed toward decontamination and decommissioning (D&D) of the former nuclear facilities and their associated sites. Closure of the liquid metal test facilities began in 1996. Results of the radiological monitoring program for the calendar year 2002 continue to indicate that there are no significant releases of radioactive material from Area IV of SSFL. All potential exposure pathways are sampled and/or monitored, including air, soil, surface water, groundwater, direct radiation, transfer of property ( land, structures, waste), and recycling. All radioactive w astes are processed for disposal at DOE disposal sites and/or other licensed sites approved by DOE for radioactive waste disposal. No liquid radioactive wastes are released into the environment, and no structural debris from buildings w as transferred to municipal landfills or recycled in 2002.« less

An assessment of enterotoxigenic Escherichia coli and Shigella vaccine candidates for infants and children.

PubMed

Walker, Richard I

2015-02-18

Despite improvements to water quality, sanitation, and the implementation of current prevention and treatment interventions, diarrhea remains a major cause of illness and death, especially among children less than five years of age in the developing world. Rotavirus vaccines have already begun making a real impact on diarrhea, but several more enteric vaccines will be necessary to achieve broader reductions of illness and death. Among the many causes of diarrheal disease, enterotoxigenic Escherichia coli (ETEC) and Shigella are the two most important bacterial pathogens for which there are no currently licensed vaccines. Vaccines against these two pathogens could greatly reduce the impact of disease caused by these infections. This review describes the approaches to ETEC and Shigella vaccines that are currently under development, including a range of both cellular and subunit approaches for each pathogen. In addition, the review discusses strategies for maximizing the potential benefit of these vaccines, which includes the feasibility of co-administration, consolidation, and combination of vaccine candidates, as well as issues related to effective administration of enteric vaccines to infants. Recent impact studies indicate that ETEC and Shigella vaccines could significantly benefit global public health. Either vaccine, particularly if they could be combined together or with another enteric vaccine, would be an extremely valuable tool for saving lives and promoting the health of infants and children in the developing world, as well as potentially providing protection to travelers and military personnel visiting endemic areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of chicken egg anti-F4 antibodies on performance and diarrhea incidences in enterotoxigenic Escherichia coli K88+-challenged piglets.

PubMed

Aluko, Kolawole; Velayudhan, Deepak E; Khafipour, Ehsan; Fang, Lin; Nyachoti, Martin

2017-12-01

The aim was to evaluate the effects of dietary supplementation of spay-dried whole egg containing anti-F4 antibodies (SDWE) against recombinantly produced F4 antigens in enterotoxigenic Escherichia coli K88 + (ETEC)-challenged piglets. Twenty-seven 21-d-old and individually housed piglets were randomly allotted to 3 treatments consisting of a wheat-soybean meal basal diet containing either 0 (control egg powder; CEP), 0.1% (SDWE1) or 0.4% (SDWE2) SDWE. After a 7-d adaptation period, blood samples were collected from all pigs, and pigs were weighed and orally challenged with an ETEC inoculum. Blood was sampled at 24 and 48 h post-challenge, and diarrhea incidences and scores were recorded. On d 14, all pigs were weighed and then euthanized to obtain intestinal tissue samples for histomorphology measurement. During the pre-challenge period, pigs fed the SDWE showed a linear improvement ( P  < 0.05) in average daily gain (ADG) and gain to feed ratio (G:F), but there were no differences among treatments in growth performance during the post-challenge period. Diarrhea incidences and scores, fecal shedding of ETEC, plasma urea nitrogen content and intestinal histomorphology were similar among treatments. The results show that 0.4% SDWE supported greater piglet performance before challenge although such benefits were not evident during the post-challenge period at either 0.1% or 0.4% supplementation.

Independent predictors of morbidity and mortality in blunt colon trauma.

PubMed

Ricciardi, R; Paterson, C A; Islam, S; Sweeney, W B; Baker, S P; Counihan, T C

2004-01-01

We sought to determine the impact of (1) grade of the colon injury, (2) the formation of an ostomy, and (3) associated injuries on outcomes such as morbidity and mortality after blunt colon injuries. We retrospectively reviewed 16,814 cases of blunt abdominal trauma. Patients with colonic injuries were selected and charts reviewed for demographic, clinical, and outcomes data. Injuries were grouped by the Colon Injury Scale (grades I-V). Independent risk factors of morbidity included spine and lung injuries, as well as increased age. A higher grade of colon injury trended toward a significant association with intra-abdominal complications. Independent risk factors of mortality included liver, heart, and lung injuries, as well as intracerebral blood and female gender. The grade of colon injury, the formation of an ostomy, and management of the colon trauma did not independently predict increased intra-abdominal complications, morbidity, or mortality. These results indicate that patients afflicted with blunt colon trauma experience a high rate of morbidity and mortality from associated injuries and or increased age. Treatment regimens directed at these factors will be most helpful in reducing the high morbidity and mortality after blunt colon trauma. Factors such as ostomy formation and management strategy are not associated with increased morbidity or mortality after blunt colon trauma.

76 FR 76961 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

... Power Company. Description: ETEC and NTEC PSA to be effective 12/17/2010. Filed Date: 11/30/11...: Southwestern Electric Power Company. Description: TexLa ERCOT Restated PSA to be effective 12/17/2010. Filed...

Patient Hand Colonization With MDROs Is Associated with Environmental Contamination in Post-Acute Care.

PubMed

Patel, Payal K; Mantey, Julia; Mody, Lona

2017-09-01

We assessed multidrug-resistant organism (MDRO) patient hand colonization in relation to the environment in post-acute care to determine risk factors for MDRO hand colonization. Patient hand colonization was significantly associated with environmental contamination. Risk factors for hand colonization included disability, urinary catheter, recent antibiotic use, and prolonged hospital stay. Infect Control Hosp Epidemiol 2017;38:1110-1113.

[Preoperatiove Airway Bacterial Colonization: the Missing Link between Non-small Cell Lung Cancer Following Lobectomy and Postoperative Pneumonia?

PubMed

Gao, Ke; Lai, Yutian; Huang, Jian; Wang, Yifan; Wang, Xiaowei; Che, Guowei

2017-04-20

Surgical procedure is the main method of treating lung cancer. Meanwhile, postoperative pneumonia (POP) is the major cause of perioperative mortality in lung cancer surgery. The preoperative pathogenic airway bacterial colonization is an independent risk factor causing postoperative pulmonary complications (PPC). This cross-sectional study aimed to explore the relationship between preoperative pathogenic airway bacterial colonization and POP in lung cancer and to identify the high-risk factors of preoperative pathogenic airway bacterial colonization. A total of 125 patients with non-small cell lung cancer (NSCLC) underwent thoracic surgery in six hospitals of Chengdu between May 2015 and January 2016. Preoperative pathogenic airway bacterial colonization was detected in all patients via fiber bronchoscopy. Patients' PPC, high-risk factors, clinical characteristics, and the serum surfactant protein D (SP-D) level were also analyzed. The incidence of preoperative pathogenic airway bacterial colonization among NSCLC patients was 15.2% (19/125). Up to 22 strains were identified in the colonization positive group, with Gram-negative bacteria being dominant (86.36%, 19/22). High-risk factors of pathogenic airway bacterial colonization were age (≥75 yr) and smoking index (≥400 cigarettes/year). PPC incidence was significantly higher in the colonization-positive group (42.11%, 8/19) than that in the colonization-negative group (16.04%, 17/106)(P=0.021). POP incidence was significantly higher in the colonization-positive group (26.32%, 5/19) than that in the colonization-negative group (6.60%, 7/106)(P=0.019). The serum SP-D level of patients in the colonization-positive group was remarkably higher than that in the colonization-negative group [(31.25±6.09) vs (28.17±5.23)](P=0.023). The incidence of preoperative pathogenic airway bacterial colonization among NSCLC patients with POP was 41.67% (5/12). This value was 3.4 times higher than that among the patients without POP (OR=3.363, 95%CI: 1.467-7.711). An intimate correlation was observed between POP and pathogenic airway bacterial colonization in lung cancer. The high-risk factors of pathogenic airway bacterial colonization were age and smoking index.

A PCR technique to detect enterotoxigenic and verotoxigenic Escherichia coli in boar semen samples.

PubMed

Bussalleu, E; Pinart, E; Yeste, M; Briz, M; Sancho, S; Torner, E; Bonet, S

2012-08-01

In semen, bacteria's isolation from a pure culture is complex, laborious and easily alterable by the presence of antibiotics and inhibitors. We developed a PCR technique to detect the presence of the enterotoxigenic (ETEC) and verotoxigenic Escherichia coli (VTEC) (strains with high prevalence in the swine industry) in semen by adapting the protocols developed by Zhang et al. (2007) and Yilmaz et al. (2006). We artificially inoculated extended semen samples at different infective concentrations of bacteria (from 10(2) to 10(8) bacteria ml(-1)) with two enterotoxigenic and verotoxigenic strains, and performed two multiplex and one conventional PCR. This technique proved to be a quick, useful and reliable tool to detect the presence of ETEC and VTEC up to an infective dose of 10(5) bacteria ml(-1) in semen. Copyright © 2011 Elsevier Ltd. All rights reserved.

Diarrheal and Respiratory Illness Surveillance During US-RP Balikatan 2014.

PubMed

Velasco, John M; Valderamat, Maria T; Nogrado, Kathyleen; Wongstitwilairoong, Tippa; Swierczewski, Brett; Bodhidatta, Ladaporn; Lertsethtakarn, Paphavee; Klungthong, Chonticha; Fernandez, Stefan; Mason, Carl; Yoon, In-Kyu; Macareo, Louis

2015-06-01

Diarrheal and respiratory illness surveillance was conducted during the 2014 Republic of the Philippines-U.S. Exercise Balikatan in the Philippines. Seven stool and three respiratory specimens that met the inclusion criteria were collected. Diarrhea stool specimens were tested with commercial enzyme-linked immunosorbent assay kits and real-time polymerase chain reaction (PCR) for 12 viral, bacterial, and protozoan pathogens. Campylobacter, enterotoxigenic Escherichia coli (ETEC), and enteropathogenic Escherichia coli (EPEC) were detected in four of seven (57%), two of seven (29%), and four of seven (57%) specimens, respectively. There were co-infections of EPEC and ETEC in two cases and EPEC and Campylobacter spp. in one case. Respiratory samples were tested using RT-PCR. One of three samples was positive for influenza B. Laboratory-based surveillance is important in determining causative agents for illnesses experienced by military personnel during deployment. Development of vaccines for enteric diseases should be expedited to mitigate their impact on operational readiness.

Flagellin and F4 fimbriae have opposite effects on biofilm formation and quorum sensing in F4ac+ enterotoxigenic Escherichia coli.

PubMed

Zhou, Mingxu; Guo, Zhiyan; Yang, Yang; Duan, Qiangde; Zhang, Qi; Yao, Fenghua; Zhu, Jun; Zhang, Xinjun; Hardwidge, Philip R; Zhu, Guoqiang

2014-01-10

Bacteria that form biofilms are often highly resistant to antibiotics and are capable of evading the host immune system. To evaluate the role of flagellin and F4 fimbriae on biofilm formation by enterotoxigenic Escherichia coli (ETEC), we deleted the fliC (encoding the major flagellin protein) and/or the faeG (encoding the major subunit of F4 fimbriae) genes from ETEC C83902. Biofilm formation was reduced in the fliC mutant but increased in the faeG mutant, as compared with the wild-type strain. The expression of AI-2 quorum sensing associated genes was regulated in the fliC and faeG mutants, consistent with the biofilm formation of these strains. But, deleting fliC and/or faeG also inhibited AI-2 quorum sensing activity. Copyright © 2013 Elsevier B.V. All rights reserved.

Rhizobial Nodulation Factors Stimulate Mycorrhizal Colonization of Nodulating and Nonnodulating Soybeans.

PubMed

Xie, Z. P.; Staehelin, C.; Vierheilig, H.; Wiemken, A.; Jabbouri, S.; Broughton, W. J.; Vogeli-Lange, R.; Boller, T.

1995-08-01

Legumes form tripartite symbiotic associations with noduleinducing rhizobia and vesicular-arbuscular mycorrhizal fungi. Co-inoculation of soybean (Glycine max [L.] Merr.) roots with Bradyrhizobium japonicum 61-A-101 considerably enhanced colonization by the mycorrhizal fungus Glomus mosseae. A similar stimulatory effect on mycorrhizal colonization was also observed in nonnodulating soybean mutants when inoculated with Bradyrhizobium japonicum and in wild-type soybean plants when inoculated with ineffective rhizobial strains, indicating that a functional rhizobial symbiosis is not necessary for enhanced mycorrhiza formation. Inoculation with the mutant Rhizobium sp. NGR[delta]nodABC, unable to produce nodulation (Nod) factors, did not show any effect on mycorrhiza. Highly purified Nod factors also increased the degree of mycorrhizal colonization. Nod factors from Rhizobium sp. NGR234 differed in their potential to promote fungal colonization. The acetylated factor NodNGR-V (MeFuc, Ac), added at concentrations as low as 10-9 M, was active, whereas the sulfated factor, NodNGR-V (MeFuc, S), was inactive. Several soybean flavonoids known to accumulate in response to the acetylated Nod factor showed a similar promoting effect on mycorrhiza. These results suggest that plant flavonoids mediate the Nod factor-induced stimulation of mycorrhizal colonization in soybean roots.

Rhizobial Nodulation Factors Stimulate Mycorrhizal Colonization of Nodulating and Nonnodulating Soybeans.

PubMed Central

Xie, Z. P.; Staehelin, C.; Vierheilig, H.; Wiemken, A.; Jabbouri, S.; Broughton, W. J.; Vogeli-Lange, R.; Boller, T.

1995-01-01

Legumes form tripartite symbiotic associations with noduleinducing rhizobia and vesicular-arbuscular mycorrhizal fungi. Co-inoculation of soybean (Glycine max [L.] Merr.) roots with Bradyrhizobium japonicum 61-A-101 considerably enhanced colonization by the mycorrhizal fungus Glomus mosseae. A similar stimulatory effect on mycorrhizal colonization was also observed in nonnodulating soybean mutants when inoculated with Bradyrhizobium japonicum and in wild-type soybean plants when inoculated with ineffective rhizobial strains, indicating that a functional rhizobial symbiosis is not necessary for enhanced mycorrhiza formation. Inoculation with the mutant Rhizobium sp. NGR[delta]nodABC, unable to produce nodulation (Nod) factors, did not show any effect on mycorrhiza. Highly purified Nod factors also increased the degree of mycorrhizal colonization. Nod factors from Rhizobium sp. NGR234 differed in their potential to promote fungal colonization. The acetylated factor NodNGR-V (MeFuc, Ac), added at concentrations as low as 10-9 M, was active, whereas the sulfated factor, NodNGR-V (MeFuc, S), was inactive. Several soybean flavonoids known to accumulate in response to the acetylated Nod factor showed a similar promoting effect on mycorrhiza. These results suggest that plant flavonoids mediate the Nod factor-induced stimulation of mycorrhizal colonization in soybean roots. PMID:12228558

Risk factors for colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae in healthcare students on clinical assignment abroad: A prospective study.

PubMed

Angelin, Martin; Forsell, Joakim; Granlund, Margareta; Evengård, Birgitta; Palmgren, Helena; Johansson, Anders

2015-01-01

The increase of antibiotic resistance in clinically important bacteria is a worldwide threat, especially in healthcare environments. International travel is a risk factor for gut colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). The risk for healthcare students of being colonized with ESBL-PE when participating in patient-related work abroad has not been previously investigated. Swedish healthcare students travelling for pre-clinical and clinical courses outside Scandinavia submitted faecal samples and survey data before and after travel. The faecal samples were screened for ESBL-PE and carbapenemase-producing Enterobacteriaceae (CPE). Screening results and survey data were analysed to identify risk factors for colonization. In the 99 subjects who submitted a full set of samples, 35% were colonized with a new ESBL-PE strain during travel. No CPE was found. The most important risk factor for ESBL-PE colonization was travel destination, and the highest colonization rate was found in the South-East Asia region. Antibiotic treatment during travel was an independent risk factor for ESBL-PE colonization but patient-related work was not significantly associated with an increased risk. Patient-related work abroad was not a risk factor for ESBL-PE suggesting that transmission from patients is uncommon. Pre-travel advice on avoiding unnecessary antibiotic treatment during travel is recommended. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fimbrial subunit protein FaeG expressed in transgenic tobacco inhibits the binding of F4ac enterotoxigenic Escherichia coli to porcine enterocytes.

PubMed

Joensuu, Jussi J; Kotiaho, Mirkka; Riipi, Tero; Snoeck, Veerle; Palva, E Tapio; Teeri, Teemu H; Lång, Hannu; Cox, Eric; Goddeeris, Bruno M; Niklander-Teeri, Viola

2004-06-01

Plants offer a promising alternative for the production of foreign proteins for pharmaceutical purposes in tissues that are consumed as food and/or feed. Our long-term strategy is to develop edible vaccines against piglet diarrhoea caused by enterotoxigenic Escherichia coli (F4 ETEC) in feed plants. In this work, we isolated a gene, faeG, encoding for a major F4ac fimbrial subunit protein. Our goal was to test whether the FaeG protein, when isolated from its fimbrial background and produced in a plant cell, would retain the key properties of an oral vaccine, that is, stability in gastrointestinal conditions, binding to intestinal receptors and inhibition of the F4 ETEC attachment. For this purpose, tobacco was first transformed with a faeG construct that included a transit peptide encoding sequence to target the FaeG protein to the chloroplast. The best transgenic lines produced FaeG protein in amounts of 1% total soluble protein. The stability of the plant-produced FaeG was tested in fluids simulating piglet gastric (SGF) and intestinal (SIF) conditions. Plant-produced FaeG proved to be stable up to 2 h under these conditions. The binding and inhibition properties were tested with isolated piglet villi. These results showed that the plant-produced FaeG could bind to the receptors on the villi and subsequently inhibit F4 ETEC binding in a dose-dependent manner. Thus, the first two prerequisites for the development of an oral vaccine have been met.

Towards Rational Design of a Toxoid Vaccine against the Heat-Stable Toxin of Escherichia coli

PubMed Central

Taxt, Arne M.; Diaz, Yuleima; Aasland, Rein; Clements, John D.; Nataro, James P.; Sommerfelt, Halvor

2016-01-01

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrheal disease and death in children <5 years old. ETEC strains that express the heat-stable toxin (ST), with or without the heat-labile toxin, are among the four most important diarrhea-causing pathogens. This makes ST an attractive target for an ETEC vaccine. An ST vaccine should be nontoxic and elicit an immune response that neutralizes native ST without cross-reacting with the human endogenous guanylate cyclase C receptor ligands. To identify variants of ST with no or low toxicity, we screened a library of all 361 possible single-amino-acid mutant forms of ST by using the T84 cell assay. Moreover, we identified mutant variants with intact epitopes by screening for the ability to bind neutralizing anti-ST antibodies. ST mutant forms with no or low toxicity and intact epitopes are termed toxoid candidates, and the top 30 candidates all had mutations of residues A14, N12, and L9. The identification of nontoxic variants of L9 strongly suggests that it is a novel receptor-interacting residue, in addition to the previously identified N12, P13, and A14 residues. The screens also allowed us to map the epitopes of three neutralizing monoclonal antibodies, one of which cross-reacts with the human ligand uroguanylin. The common dominant epitope residue for all non-cross-reacting antibodies was Y19. Our results suggest that it should be possible to rationally design ST toxoids that elicit neutralizing immune responses against ST with minimal risk of immunological cross-reactivity. PMID:26883587

Structural and functional insight into the carbohydrate receptor binding of F4 fimbriae-producing enterotoxigenic Escherichia coli.

PubMed

Moonens, Kristof; Van den Broeck, Imke; De Kerpel, Maia; Deboeck, Francine; Raymaekers, Hanne; Remaut, Han; De Greve, Henri

2015-03-27

Enterotoxigenic Escherichia coli (ETEC) strains are important causes of intestinal disease in humans and lead to severe production losses in animal farming. A range of fimbrial adhesins in ETEC strains determines host and tissue tropism. ETEC strains expressing F4 fimbriae are associated with neonatal and post-weaning diarrhea in piglets. Three naturally occurring variants of F4 fimbriae (F4ab, F4ac, and F4ad) exist that differ in the primary sequence of their major adhesive subunit FaeG, and each features a related yet distinct receptor binding profile. Here the x-ray structure of FaeGad bound to lactose provides the first structural insight into the receptor specificity and mode of binding by the poly-adhesive F4 fimbriae. A small D'-D″-α1-α2 subdomain grafted on the immunoglobulin-like core of FaeG hosts the carbohydrate binding site. Two short amino acid stretches Phe(150)-Glu(152) and Val(166)-Glu(170) of FaeGad bind the terminal galactose in the lactosyl unit and provide affinity and specificity to the interaction. A hemagglutination-based assay with E. coli expressing mutant F4ad fimbriae confirmed the elucidated co-complex structure. Interestingly, the crucial D'-α1 loop that borders the FaeGad binding site adopts a different conformation in the two other FaeG variants and hints at a heterogeneous binding pocket among the FaeG serotypes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Colonic injuries (primary repair and proximal colostomy).

PubMed

Tripathi, Munishwar D; Mishra, Brijesh

2005-01-01

This paper compares the outcome of colonic injuries (primary repair and proximal colostomy) in 94 cases. It concludes that certain risk factors are of predictive value in case of colon injuries (eg, gross fecal contamination, more than two visceral injuries, more than four units of blood transfusion, and extensive colonic injuries) irrespective of type of operation performed. Primary repair is debatable; however, in the present antibiotic era, it is safe and less costly than the two-stage procedure of proximal colostomy with repair. Primary repair can be performed in almost all cases except in certain selected cases that are decided on the table, taking into account the above risks factors. Mortality in cases of colonic injuries is associated with risk factors rather than colonic injury itself.

Applicability of an established management algorithm for colon injuries following blunt trauma.

PubMed

Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Shahan, Charles P; Cullinan, Darren R; Fabian, Timothy C; Croce, Martin A

2013-02-01

Operative management at our institution for all colon injuries have followed a defined algorithm (ALG) based on risk factors originally identified for penetrating injuries. The purpose of this study was to evaluate the applicability of the ALG to blunt colon injuries. Patients with blunt colon injuries during 13 years were identified. As per the ALG, nondestructive (ND) injuries are treated with primary repair. Patients with destructive wounds (serosal tear of ≥50% colon circumference, mesenteric devascularization, and perforations) and concomitant risk factors (transfusion of >6 U packed red blood cells and/or presence of significant comorbidities) are diverted, while patients with no risk factors undergo resection plus anastomosis (RA). Outcomes included suture line failure (SLF), abscess, and mortality. Stratification analysis was performed to determine additional risk factors in the management of blunt colon injuries. A total 151 patients were identified: 76 with destructive injuries and 75 with ND injuries. Of those with destructive injuries, 44 (59%) underwent RA and 29 (39%) underwent diversion. All ND injuries underwent primary repair. Adherence to the ALG was 95%: three patients with destructive injuries underwent primary repair, and five patients with risk factors underwent RA. There were three SLFs (2%) (one involved deviation from the ALG) and eight abscesses (5%). Colon-related mortality was 2.1%. Stratification analysis based on mesenteric involvement, degree of shock, and need for abbreviated laparotomy failed to identify additional risk factors for SLF following RA for blunt colon injuries. Adherence to an ALG, originally defined for penetrating colon injuries, simplified the management of blunt colon injuries. ND injuries should be primarily repaired. For destructive wounds, management based on a defined ALG achieves an acceptably low morbidity and mortality rate. Prognostic/epidemiologic study, level III; therapeutic study, level IV.

A systematic review and meta-analysis of the epidemiology of pathogenic Escherichia coli of calves and the role of calves as reservoirs for human pathogenic E. coli.

PubMed

Kolenda, Rafał; Burdukiewicz, Michał; Schierack, Peter

2015-01-01

Escherichia coli bacteria are the most common causes of diarrhea and septicemia in calves. Moreover, calves form a major reservoir for transmission of pathogenic E. coli to humans. Systematic reviews and meta-analyses of publications on E. coli as calf pathogens and the role of calves as reservoir have not been done so far. We reviewed studies between 1951 and 2013 reporting the presence of virulence associated factors (VAFs) in calf E. coli and extracted the following information: year(s) and country of sampling, animal number, health status, isolate number, VAF prevalence, serotypes, diagnostic methods, and biological assays. The prevalence of VAFs or E. coli pathotypes was compared between healthy and diarrheic animals and was analyzed for time courses. Together, 106 papers with 25,982 E. coli isolates from 27 countries tested for VAFs were included. F5, F17, and F41 fimbriae and heat-stable enterotoxin (ST) - VAFs of enterotoxigenic E. coli (ETEC) were significantly associated with calf diarrhea. On the contrary, ETEC VAF F4 fimbriae and heat-labile enterotoxin as well as enteropathogenic (EPEC), Shiga toxin-producing (STEC), and enterohemorrhagic E. coli (EHEC) were not associated with diarrhea. The prevalence increased overtime for ST-positive isolates, but decreased for F5- and STEC-positive isolates. Our study provides useful information about the history of scientific investigations performed in this domain so far, and helps to define etiological agents of calf disease, and to evaluate calves as reservoir hosts for human pathogenic E. coli.

Fecal contamination of drinking water supplies in and around Chandigarh and correlation with acute gastroenteritis.

PubMed

Neelam, Taneja; Malkit, Singh; Pooja, Rao; Manisha, Biswal; Shiva, Priya; Ram, Chander; Meera, Sharma

2012-12-01

Acute gastroenteritis due to Vibrio cholerae and Enterotoxigenic E. coli is a common problem faced in the hot and humid summer months in north India. The study was undertaken to evaluate drinking water supplies for fecal coliforms, V. cholerae and Enterotoxigenic E. coli in urban, semiurban and rural areas in and around Chandigarh and correlate with occurrence of acute gastroenteritis occurring from the same region. Drinking water sample were collected from various sources from April to October 2004 from a defined area. Samples were tested for fecal coliforms and E. coli count. E. coli were screened for heat labile toxin (LT) also. Stool samples from cases of acute gastroenteritis from the same region and time were collected and processed for V. cholerae, Enterotoxigenic E. coli (ETEC) and others like Salmonella, Shigella and Aeromonas spp. A total of 364 water samples were collected, (251 semi urban, 41 rural and 72 from urban areas). 116 (31.8%) samples were contaminated with fecal coliforms (58.5% rural, 33.4% semiurban and 11.1% of samples from urban areas). E. coli were grown from 58 samples. Ninety two isolates of E. coli were tested for enterotoxins of which 8 and 24 were positive for LT and ST respectively. V. cholerae were isolated from 2 samples during the outbreak investigation. Stored water samples showed a significantly higher level of contamination and most of Enterotoxigenic E. coli were isolated from stored water samples. A total of 780 acute gastroenteritis cases occurred; 445 from semiurban, 265 rural and 70 from urban areas. Out of 189 stool samples submitted, ETEC were the commonest (30%) followed by V. cholerae (19%), Shigellae (8.4%), Salmonellae (2.1%) and Aeromonas (2.6%). ST-ETEC (40/57) were commoner than LT-ETEC (17/57). In the present study, high levels of contamination of drinking water supplies (32.1%) correlated well with cases of acute gastroenteritis. Majority of cases of acute gastroenteritis occurred in the semi urban corresponding with high level of contamination (33.4%). The highest level of water contamination was seen in rural areas (58.5%) but the number of acute gastroenteritis cases were lesser (33.9%) as ponds were infrequently used for drinking purpose. Safer household water storage and treatment is recommended to prevent acute gastroenteritis, together with point-of-use water quality monitoring.

Skin Colonization by Malassezia spp. in hospitalized neonates and infants in a tertiary care centre in North India.

PubMed

Gupta, Prerna; Chakrabarti, Arunaloke; Singhi, Sunit; Kumar, Praveen; Honnavar, Prasanna; Rudramurthy, Shivaprakash M

2014-10-01

Malassezia, a skin colonizer, is associated with multiple skin disorders in adults, and cephalic pustulosis and folliculitis in children. It can cause fungemia in infants and neonates. The time and pattern of colonization, risk factors associated with colonization and causing fungemia in children, are not well understood. The prospective cohort study was conducted to determine the rate of Malassezia species colonization and associated factors in hospitalized neonates and infants. Consecutive 50 neonates and infants admitted in neonatal and pediatric intensive care units were studied. The skin swabs were collected on the day of admission and every fifth day, thereafter, till the patient was discharged or died. Putative risk factors for the colonization of Malassezia species were recorded. Isolates were identified by phenotypic methods and sequencing of the D1 and D2 region of rDNA. Neonates were not colonized at the time of entry in neonatal ICU or at birth. Nineteen (38 %) neonates were colonized with Malassezia species during their hospital stay. Among the infants, three (6 %) came to ICU with Malassezia colonization and 26 (52 %) acquired Malassezia during ICU stay. Mechanical ventilation, duration of hospital stay, central venous catheterization, and antifungal therapy were the significantly associated factors for colonization. Malassezia furfur was the most common species isolated from the skin of infants and neonates. Colonization by Malassezia species in infants and neonates in a hospital is not uncommon and can be a potential source of nosocomial infection.

Spatial and environmental correlates of organism colonization and infection in the neonatal intensive care unit.

PubMed

Goldstein, Neal D; Tuttle, Deborah; Tabb, Loni P; Paul, David A; Eppes, Stephen C

2018-05-01

To examine organism colonization and infection in the neonatal intensive care unit as a result of environmental and spatial factors. A retrospective cohort of infants admitted between 2006 and 2015 (n = 11 428), to assess the relationship between location and four outcomes: methicillin-resistant Staphylococcus aureus (MRSA) colonization; culture-confirmed late-onset sepsis; and, if intubated, endotracheal tube colonization with Pseudomonas aeruginosa or Klebsiella pneumonia. Independent risk factors were identified with mixed-effects logistic regression models and Moran's I for spatial autocorrelation. All four outcomes statistically clustered by location; neighboring colonization also influenced risk of MRSA (p < 0.05). For P. aeruginosa, being in a location with space for more medical equipment was associated with 2.61 times the odds of colonization (95% CrI: 1.19, 5.78). Extrinsic factors partially explained risk for neonatal colonization and infection. For P. aeruginosa, infection prevention efforts at locations with space for more equipment may lower future colonization.

Risk factors for fecal colonization with multiple distinct strains of Escherichia coli among long-term care facility residents.

PubMed

Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N

2009-05-01

Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging.

Risk Factors for Fecal Colonization with Multiple Distinct Strains of Escherichia coli Among Long-Term Care Facility Residents

PubMed Central

Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N.

2009-01-01

Of 49 long-term care facility residents, 21 (43%) were colonized with two or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest future efforts to efficiently identify diversity of colonizing strains will be challenging. PMID:19292660

Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

PubMed

Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

2016-09-01

Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage.

Epidemiology and Characteristics of Escherichia coli Sequence Type 131 (ST131) from Long-Term Care Facility Residents Colonized Intestinally with Fluoroquinolone-Resistant Escherichia coli

PubMed Central

Han, Jennifer H.; Garrigan, Charles; Johnston, Brian; Nachamkin, Irving; Clabots, Connie; Bilker, Warren B.; Santana, Evelyn; Tolomeo, Pam; Maslow, Joel; Myers, Janice; Carson, Lesley; Lautenbach, Ebbing; Johnson, James R.

2016-01-01

The objective of this study was to evaluate molecular and epidemiologic factors associated with Escherichia coli sequence type 131 (ST131) among long-term care facility (LTCF) residents who acquired gastrointestinal tract colonization with fluoroquinolone-resistant E. coli (FQREC). Colonizing isolates from 37 residents who newly developed FQREC colonization at three LTCFs from 2006–2008 were evaluated. Twenty-nine (78%) of 37 total FQREC colonizing isolates were ST131. Most ST131 isolates had a distinctive combination of gyrA and parC replacement mutations. The ST131 and non-ST131 isolates differed significantly for the prevalence of many individual virulence factors but not for the proportion that qualified molecularly as extraintestinal pathogenic E. coli (ExPEC) or aggregate virulence factor scores. E. coli ST131 was highly prevalent among LTCF residents with FQREC colonization. Future studies should determine the risk factors for infection among ST131-colonized residents, and assess the potential for increased transmissibility of ST131 in the long-term care setting. PMID:27939288

Clinical associations and prevalence of Scedosporium spp. in Australian cystic fibrosis patients: identification of novel risk factors?

PubMed

Blyth, Christopher C; Middleton, Peter G; Harun, Azian; Sorrell, Tania C; Meyer, Wieland; Chen, Sharon C-A

2010-11-01

Risk factors for the association of Scedosporium in cases of cystic fibrosis (CF) and its clinical implications are poorly understood. Clinical, lung function and laboratory data of adult CF patients in Sydney (April 2008-March 2009) were prospectively analysed for such risk factors. Expectorated sputa were cultured for bacteria and examined for fungi using standard mycological and Scedosporium-selective media, and by an internal transcribed spacer region-targeted multiplex PCR assay. Scedosporium spp. (n = 4 each of Scedosporium prolificans, Scedosporium aurantiacum and Pseudallescheria boydii/ Scedosporium apiospermum complex [non-S. aurantiacum]) were recovered from 12 of 69 (17.4%) patients. Samples of 11 of the patients yielded isolates on Scedosporium- selective media (vs. 6 [8.7%] by non-selective culture) and one additional patient was noted by PCR. Of these patients, 83.3% were co-colonized with other moulds, most frequently Aspergillus fumigatus. Colonization was not associated with best FEV₁/predicted, corticosteroid or antifungal therapies. By univariate analysis, patients with Scedosporium colonization were significantly less likely to be colonized with mucoid Pseudomonas aeruginosa (P = 0.025), while prior therapy with antistaphylococcal penicillins was a risk factor for colonization (P = 0.045). Bacterial colonization and antimicrobial exposure likely influence Scedosporium colonization, which is optimally detected with selective media. Studies are required to confirm independent risk factors for Scedosporium colonization and to determine its impact on lung disease.

Antibiotic consumption and Enterobacteriaceae skin colonization in hospitalized adults.

PubMed

Kirby, A; Berry, C; West, R

2017-01-01

Enterobacteriaceae are increasingly antibiotic resistant, and skin colonization may contribute to their spread in hospitals. This study screened 100 hospitalized adults for Enterobacteriaceae skin colonization, and assessed potential risk factors, including antibiotic consumption. Multi-variable analysis found that antibiotic consumption whilst an inpatient [odds ratio (OR) 3.16, 95% confidence interval (CI) 1.19-8.4] and male sex (OR 2.92, 95% CI 1.06-8.4) were risk factors for Enterobacteriaceae skin colonization. If these risk factors are confirmed, work to understand the biological mechanism involved may lead to the development of interventions to prevent Enterobacteriaceae skin colonization. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases.

PubMed

Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Andersson, Roland

2016-10-01

To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion. Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS. Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis. LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

Results of Four-Year Rectal Vancomycin-Resistant Enterococci Surveillance in a Pediatric Hematology-Oncology Ward: From Colonization to Infection.

PubMed

Aktürk, Hacer; Sütçü, Murat; Somer, Ayper; Karaman, Serap; Acar, Manolya; Ünüvar, Ayşegül; Anak, Sema; Karakaş, Zeynep; Özdemir, Aslı; Sarsar, Kutay; Aydın, Derya; Salman, Nuran

2016-09-05

To investigate the clinical impact of vancomycin-resistant enterococci (VRE) colonization in patients with hematologic malignancies and associated risk factors. Patients colonized and infected with VRE were identified from an institutional surveillance database between January 2010 and December 2013. A retrospective case-control study was performed to identify the risk factors associated with development of VRE infection in VRE-colonized patients. Fecal VRE colonization was documented in 72 of 229 children (31.4%). Seven VRE-colonized patients developed subsequent systemic VRE infection (9.7%). Types of VRE infections included bacteremia (n=5), urinary tract infection (n=1), and meningitis (n=1). Enterococcus faecium was isolated in all VRE infections. Multivariate analysis revealed severe neutropenia and previous bacteremia with another pathogen as independent risk factors for VRE infection development in colonized patients [odds ratio (OR): 35.4, confidence interval (CI): 1.7-72.3, p=0.02 and OR: 20.6, CI: 1.3-48.6, p=0.03, respectively]. No deaths attributable to VRE occurred. VRE colonization has important consequences in pediatric cancer patients.

Corticotropin-releasing factor stimulates colonic motility via muscarinic receptors in the rat

PubMed Central

Kim, Kyung-Jo; Kim, Ki Bae; Yoon, Soon Man; Han, Joung-Ho; Chae, Hee Bok; Park, Seon Mee; Youn, Sei Jin

2017-01-01

AIM To measure exogenous corticotropin-releasing factor (CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected. After recording basal colonic motility, hexamethonium, phentolamine, propranolol, atropine and tetrodotoxin were infused into the isolated colon. Initially, only the test drug was infused; then, CRF was added. The motility index was expressed as percentage change over basal level. RESULTS Administration of 1.4, 14.4, 144 and 288 pmol/L CRF progressively increased colonic motility in the proximal and distal colon. Infusion of atropine or tetrodotoxin reduced CRF-induced motility of both the proximal and distal colon, whereas hexamethonium, phentolamine and propranolol had no effect. CONCLUSION CRF-induced colonic motility appears to be mediated by local cholinergic signaling via muscarinic receptors. Muscarinic receptors are potential targets for counteracting CRF-induced colonic hypermotility. PMID:28638222

The Gambia and Bangladesh: the seasons and diarrhoea.

PubMed

Rowland, M G

1986-09-01

Climactic factors in the Gambia and Bangladesh have an important impact on the incidence of diarrheal disease. Both countries share some common characteristics in climate, including a cool dry winter of 3 months followed by a hot dry spring and hot wet summers of 5-7 months in length. The main difference is in the amount of rainfall. The Gambia may have 20-30 inches of rain each year; Bangladesh usually has up to 4-5 times this amount. In the Gambia, drought is a recurring problem; floods is the problem in Bangladesh. A study in the Gambia found a close link between the time of the annual peak in diarrhea in young children and the summer rains. A 2nd peak of diarrhea in the winter also was significant and was shown to coincide with a short period of intense transmission of rotavirus. Of the enteric infections of childhood, the enterotoxigenic "Escherichia coli" (ETEC), that is those producing heat-stable toxin (ST) were found to be the most important etiological agents of diarrhea in both countries, with a peak during the rains. In rural Gambia, water is obtained almost exclusively from surface wells, 15-20 meters deep. It was found that, although this water was fecally contaminated throughout the year, levels of contamination increased by up to 100 times with 1-2 days of the start of the rains because excreta is washed into the wells. It also was clear that contaminated water and domestic environment contribute to contamination of children's food. The high level of contamination of food during the summer coincided with the time of high diarrhea prevalence. In Bangladesh it was shown that the incidence of ETEC diarrhea in infants was positively correlated with the frequency of consumption of weaning foods contaminated with fecal coliforms. The seasonal peak of ETEC diarrhea coincided with the time when food was most contaminated due to higher bacterial growth caused by high temperatures. Cholera is endemic in many areas of Bangladesh but not in the Gambia. Though similar some other diarrheal diseases in showing a rainy season peak, the timing of peaks of cholera incidence can and has changed from year to year in Bangladesh. The reason for this and the variable occurence of a less marked pre-rains peak of cholera is unknown. During the main farming season, mothers have less time for breastfeeding. Smaller amounts of breast milk were consumed by breastfeeding infants at this time of year coinciding with poorer maternal nutritional status. This also was the season of poorest nutritional status in children, leading to increased duration and, perhaps, severity of diarrhea. Personal hygiene, attitudes toward breastfeeding, and weaning practices are important, non-seasonal factors in diarrheal diseases. To be more effective, health education messages could be varied according to the season, for different problems occur at various times of the year.

The effects of live yeast Saccharomyces cerevisiae on postweaning diarrhea, immune response, and growth performance in weaned piglets.

PubMed

Trckova, M; Faldyna, M; Alexa, P; Sramkova Zajacova, Z; Gopfert, E; Kumprechtova, D; Auclair, E; D'Inca, R

2014-02-01

The effects of live yeast Saccharomyces cerevisiae (strain CNCM I-4407, 10(10) cfu/g; Actisaf; Lesaffre Feed Additives, Marcq-en-Baroeul, France) on the severity of diarrhea, immune response, and growth performance in weaned piglets orally challenged with enterotoxigenic Escherichia coli (ETEC) strain O149:K88 were investigated. Live yeast was fed to sows and their piglets in the late gestation, suckling, and postweaning periods. Sows were fed a basal diet without (Control; n = 2) or with (Supplemented; n = 2) 1 g/kg of live yeast from d 94 of gestation and during lactation until weaning of the piglets (d 28). Suckling piglets of the supplemented sows were orally treated with 1 g of live yeast in porridge carrier 3 times a week until weaning. Weaned piglets were fed a basal starter diet without (Control; n = 19) or with (Supplemented; n = 15) 5 g of live yeast/kg feed for 2 wk. Significantly lower daily diarrhea scores (P < 0.05), duration of diarrhea (P < 0.01), and shedding of pathogenic ETEC bacteria (P < 0.05) in feces was detected in the supplemented piglets. Administration of live yeast significantly increased (P < 0.05) IgA levels in the serum of piglets. Evidence indicates that decreased infection-related stress and severity of diarrhea in yeast-fed weaned piglets positively affected their growth capacity in the postweaning period (P < 0.05). The results suggest that dietary supplementation with live yeast S. cerevisiae to sows and piglets in the late gestation, suckling, and postweaning periods can be useful in the reduction of the duration and severity of postweaning diarrhea caused by ETEC.

Antibiotic resistant Escherichia coli in southeastern Australian pig herds and implications for surveillance.

PubMed

van Breda, L K; Dhungyel, O P; Ward, M P

2018-02-01

To investigate public health implications of antibiotics to control post-weaning scours, we surveyed 22 commercial pig herds in southeastern Australia. Fifty faecal samples per herd were collected from pre- and post-weaned piglets. Presumptive Escherichia coli isolates were confirmed by MALDI-TOF MS. Isolates (n = 325) were screened for susceptibility to 19 veterinary antibiotics using MIC broth microdilution. All 325 E. coli isolates underwent further testing against 27 antibiotics used in human medicine and were screened for ETEC adhesin and enterotoxin genes (F4 (K88), F5 (K99), F6 (987P), F18, F41, STa, STb, Stx2e and LT) by multiplex PCR. Isolates identified as phenotypically resistant to third-generation cephalosporin (3GC) and aminoglycoside antibiotics were screened by multiplex PCR/reverse line blot to detect common β-lactam and aminoglycosides resistance genes, confirmed by sequencing. Twenty (6.1%) of the E. coli isolates were resistant to 3GC antibiotics and 24 (7.4%) to the aminoglycoside antibiotic gentamicin. Genetic analysis revealed six different extended spectrum β-lactamase (ESBL) genes (blaCTX-M-1, -14, -15, -27, blaSHV-12 and blaCMY-2-like genes), four of which have not been previously reported in Australian pigs. Critically, the prevalence of 3GC resistance was higher in non-pathogenic (non-ETEC) isolates and those from clinically normal (non-diarrhoeal) samples. This highlights the importance of non-ETECE. coli as reservoirs of antimicrobial resistance genes in piglet pens. Antimicrobial resistance surveillance in pig production focused on diagnostic specimens from clinically-affected animals might be potentially misleading. We recommend that surveillance for emerging antimicrobial resistance such as to 3GC antibiotics should include clinically healthy pigs. © 2017 Blackwell Verlag GmbH.

Epidemiology of bacterial pathogens associated with infectious diarrhea in Djibouti.

PubMed Central

Mikhail, I A; Fox, E; Haberberger, R L; Ahmed, M H; Abbatte, E A

1990-01-01

During a survey examining the causes of diarrhea in the East African country of Djibouti, 140 bacterial pathogens were recovered from 209 diarrheal and 100 control stools. The following pathogens were isolated at comparable frequencies from both diarrheal and control stools: enteroadherent Escherichia coli (EAEC) (10.6 versus 13%), enterotoxigenic E. coli (ETEC) (11 versus 10%), enteropathogenic E. coli (EPEC) (7.7 versus 12%), Salmonella spp. (2.9 versus 3%), and Campylobacter jejuni-C. coli (3.3 versus 5%). Surprisingly, the EAEC strains isolated did not correspond to well-recognized EPEC serogroups. No Yersinia spp., enteroinvasive E. coli, or enterohemorrhagic E. coli were isolated during the course of this study. Only the following two genera were recovered from diarrheal stools exclusively: Shigella spp. (7.7%) and Aeromonas hydrophila group organisms (3.3%). Shigella flexneri was the most common Shigella species isolated. Patients with Shigella species were of a higher average age than were controls (27 versus 13 years), while subjects with Campylobacter or Salmonella species belonged to younger age groups (2.6 and 1.6 years, respectively). Salmonella cases were more often in females. Shigella diarrhea was associated with fecal blood or mucus and leukocytes. ETEC was not associated with nausea or vomiting. Anorexia, weight loss, and fever were associated with the isolation of Salmonella and Aeromonas species. EAEC, ETEC, EPEC, and Shigella species were resistant to most drugs used for treating diarrhea in Africa, while the antibiotic most active against all bacteria tested was norfloxacin. We conclude that in Djibouti in 1989, Shigella and Aeromonas species must be considered as potential pathogens whenever they are isolated from diarrheal stools and that norfloxacin should be considered the drug of choice in adults for treating severe shigellosis and for diarrhea prophylaxis in travelers. PMID:2351738

Genotypic analysis of virulence genes and antimicrobial profile of diarrheagenic Escherichia coli isolated from diseased lambs in Iran.

PubMed

Ghanbarpour, Reza; Askari, Nasrin; Ghorbanpour, Masoud; Tahamtan, Yahya; Mashayekhi, Khoobyar; Afsharipour, Narjes; Darijani, Nasim

2017-03-01

The aim of the present study was to determine the analysis of virulence genes and antimicrobial profile of diarrheagenic Escherichia coli isolated from diseased lambs. Two hundred ninety E. coli isolates were recovered from 300 rectal swabs of diarrheic lambs and were confirmed by biochemical tests. The pathotype determination was done according to the presence of genes including f5, f41, LTI, STI, bfp, ipaH, stx 1 , stx 2 , eae, ehlyA, cnf 1 , cnf 2 , cdIII, cdIV, and f17 by PCR method. Sixty-six isolates (23.72%) possessed the STI gene and categorized into entrotoxigenic E. coli (ETEC). Nine isolates (3.1%) and five isolates (1.72%) were positive for the cnf1 and cnf2 genes which categorized into necrotoxic E. coli (NTEC). Hundred and seventeen isolates (40.34%) harbored stx 1 and/or stx 2 and classified as Shiga toxin-producing E. coli (STEC). Thirteen isolates (4.48%) were assigned to atypical entropathogenic E. coli (aEPEC) and possessed eae gene. Two isolates (0.68%) were positive for ipaH gene and were assigned to entroinvasive E. coli (EIEC). Statistical analysis showed a specific association between eae gene and STEC pathotype (P < 0.0001). The most prevalent resistance was observed against lincomycin (96.5%) and the lowest resistance was against kanamycine (56.02%), respectively. The high prevalence of STEC and ETEC indicates that diarrheic lambs represent an important reservoir for humans. ETEC may play an important role for frequent occurrence of diarrhea in lambs observed in this region. Due to high antibiotic resistance, appropriate control should be implemented in veterinary medicine to curb the development of novel resistant isolates.

Examination of enterotoxigenic Escherichia coli H10407 (colonization factor antigen I+) by scanning electron microscopy with conductive staining.

PubMed Central

Sherburne, R; Armstrong, G D

1989-01-01

We have used the scanning electron microscope to examine enterotoxigenic Escherichia coli H10407, which expresses colonization factor antigen I pili. The use of low accelerating voltages and conductive staining procedures allowed us to obtain images of colonization factor antigen I pili and other structural details which were obscured by conventional gold-coating techniques. Images PMID:2570062

Virulence factors and antimicrobial resistance of escherichia coli isolated from urinary tract of swine in southern of Brazil

PubMed Central

da Costa, Mateus Matiuzzi; Drescher, Guilherme; Maboni, Franciele; Weber, Shana; de Avila Botton, Sônia; Vainstein, Marilene Henning; Schrank, Irene Silveira; de Vargas, Agueda Castagna

2008-01-01

The present study determined the molecular and resistance patterns of E. coli isolates from urinary tract of swine in Southern of Brazil. Molecular characterization of urinary vesicle samples was performed by PCR detection of virulence factors from ETEC, STEC and UPEC. From a total of 82 E. coli isolates, 34 (38.63%) harbored one or more virulence factors. The frequency of virulence factors genes detected by PCR were: pap (10.97%), hlyA (10.97%), iha (9.75%), lt (8.53%), sta (7.31%) sfa (6.09%), f4 (4.87%), f5 (4.87%), stb (4.87%), f6 (1.21%) and f41 (1.21%). Isolates were resistant to penicillin (95.12%), lincomycin (93.9%), erythromycin (92.68%), tetracycline (90.24%), amoxicillin (82.92%), ampicillin (74.39%), josamycin (79.26%), norfloxacin (58.53%), enrofloxacin (57.31%), gentamicin (39.02%), neomycin (37.8%), apramycin (30.48%), colistine (30.48%) and cefalexin (6.09%). A number of 32 (39.02%) E. coli isolates harbored plasmids. PMID:24031300

High colonization rates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Swiss travellers to South Asia- a prospective observational multicentre cohort study looking at epidemiology, microbiology and risk factors.

PubMed

Kuenzli, Esther; Jaeger, Veronika K; Frei, Reno; Neumayr, Andreas; DeCrom, Susan; Haller, Sabine; Blum, Johannes; Widmer, Andreas F; Furrer, Hansjakob; Battegay, Manuel; Endimiani, Andrea; Hatz, Christoph

2014-10-01

International travel contributes to the worldwide spread of multidrug resistant Gram-negative bacteria. Rates of travel-related faecal colonization with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae vary for different destinations. Especially travellers returning from the Indian subcontinent show high colonization rates. So far, nothing is known about region-specific risk factors for becoming colonized. An observational prospective multicentre cohort study investigated travellers to South Asia. Before and after travelling, rectal swabs were screened for third-generation cephalosporin- and carbapenem-resistant Enterobacteriaceae. Participants completed questionnaires to identify risk factors for becoming colonized. Covariates were assessed univariately, followed by a multivariate regression. Hundred and seventy persons were enrolled, the largest data set on travellers to the Indian subcontinent so far. The acquired colonization rate with ESBL-producing Escherichia coli overall was 69.4% (95% CI 62.1-75.9%), being highest in travellers returning from India (86.8%; 95% CI 78.5-95.0%) and lowest in travellers returning from Sri Lanka (34.7%; 95% CI 22.9-48.7%). Associated risk factors were travel destination, length of stay, visiting friends and relatives, and eating ice cream and pastry. High colonization rates with ESBL-producing Enterobacteriaceae were found in travellers returning from South Asia. Though risk factors were identified, a more common source, i.e. environmental, appears to better explain the high colonization rates.

Colonic diverticulosis is not a risk factor for colonic adenoma.

PubMed

Hong, Wandong; Dong, Lemei; Zippi, Maddalena; Stock, Simon; Geng, Wujun; Xu, Chunfang; Zhou, Mengtao

2018-01-01

Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.

The role of colonic metabolism in lactose intolerance.

PubMed

He, T; Venema, K; Priebe, M G; Welling, G W; Brummer, R-J M; Vonk, R J

2008-08-01

Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

Age-related susceptibility to infection with diarrheagenic E. coli in infants from peri-urban areas of Lima, Peru

PubMed Central

Ochoa, Theresa J.; Ecker, Lucie; Barletta, Francesca; Mispireta, Mónica L.; Gil, Ana I.; Contreras, Carmen; Molina, Margarita; Amemiya, Isabel; Verastegui, Hector; Hall, Eric R.; Cleary, Thomas G.; Lanata, Claudio F.

2009-01-01

Background Diarrheagenic E. coli are being recognized as important pediatric enteropathogens worldwide. However, it is unclear whether there are differences in age-related susceptibility to specific agents, especially among infants. Methods We conducted a passive surveillance diarrhea cohort study of 1034 children from 2 to 12 months of age in Lima, Perú. Control stool samples were collected from randomly selected children without diarrhea. All samples were analyzed for common enteric pathogens and for the diarrheagenic E. coli by a multiplex real-time PCR. Results The most commonly isolated pathogens from 1065 diarrheal episodes were the diarrheagenic E. coli (31%), including enteroaggregative (15.1%) and enteropathogenic E. coli (EPEC) (7.6%). Diarrheagenic E. coli, Campylobacter and rotavirus were more frequently isolated from infants ≥ 6m. Diffusely adherent E. coli and enterotoxigenic E. coli (ETEC) were more frequently isolated in diarrheal samples than in controls in older infants (p<0.05). Children ≥ 6m infected with ETEC had a 4.56-fold increased risk for diarrhea (95% CI, 1.20 to 17.28). Persistent diarrhea was more frequent in infants < 6m (13.5% vs. 3.6%, p<0.001). Among diarrheagenic E. coli positive samples, co-infections with other pathogens were more common in diarrhea than in controls (40.1% vs. 15.6%, p<0.001). Conclusions Diarrheagenic E. coli were more frequently isolated in older infants. In this setting with high frequency of pathogen exposure and high frequency of breastfeeding, we hypothesize that the major age-related differences result from decreased exposure to milk protective factors and with increased exposure to contaminated food and water. PMID:19857163

Thermostability of the coating, antigen and immunostimulator in an adjuvanted oral capsule vaccine formulation.

PubMed

Longet, Stephanie; Aversa, Vincenzo; O'Donnell, Daire; Tobias, Joshua; Rosa, Monica; Holmgren, Jan; Coulter, Ivan S; Lavelle, Ed C

2017-12-20

Oral vaccines present an attractive alternative to injectable vaccines for enteric diseases due to ease of delivery and the induction of intestinal immunity at the site of infection. However, susceptibility to gastrointestinal proteolysis, limited transepithelial uptake and a lack of clinically acceptable adjuvants present significant challenges. A further challenge to mass vaccination in developing countries is the very expensive requirement to maintain the cold chain. We recently described the effectiveness of a Single Multiple Pill ® (SmPill ® ) adjuvanted capsule approach to enhance the effectiveness of a candidate enterotoxigenic Escherichia coli (ETEC) oral vaccine. Here it was demonstrated that this delivery system maintains the antigenicity of ETEC colonisation factor antigen I (CFA/I) and the immunostimulatory activity of the orally active α-Galactosylceramide (α-GalCer) adjuvant after storage of SmPill ® minispheres under room temperature and extreme storage conditions for several months. In addition, the internal structure of the cores of SmPill ® minispheres and antigen release features at intestinal pH were found to be preserved under all these conditions. However, changes in the surface morphology of SmPill ® minispheres leading to the antigen release at gastric pH were observed after a few weeks of storage under extreme conditions. Those modifications were prevented by the introduction of an Opadry ® White film coating layer between the core of SmPill ® minispheres and the enteric coating. Under these conditions, protection against antigen release at gastric pH was maintained even under high temperature and humidity conditions. These results support the potential of the SmPill ® minisphere approach to maintain the stability of an adjuvanted whole cell killed oral vaccine formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasmid-controlled colonization factor associated with virulence in Esherichia coli enterotoxigenic for humans.

PubMed Central

Evans, D G; Silver, R P; Evans, D J; Chase, D G; Gorbach, S L

1975-01-01

An enterotoxin-producing strain of Escherichia coli isolated from a case of cholera-like diarrhea (E. coli strain H-10407) was found to possess a surface-associated colonization factor. Colonization was manifested as the ability of small inocula (10(5) bacteria) to attain large (10(9)) populations in the infant rabbit intestine with a concomitant diarrheal response. A laboratory-passed derivative of E. coli H-10407, designated H-10407-P, failed to exhibit an increase in population in the infant rabbit and also failed to induce diarrhea. Cell-free culture supernatant fluids of E. coli H-10407 and H-10407-P produced equivalent enterotoxic responses in infant and in adult rabbits. Specific anti-colonization factor antiserum was produced by adsorbing hyperimmune anti-H-10407 serum with both heat-killed and living cells E. coli H-10407-P. This specific adsorbed serum protected infant rabbits from challenge with living E. coli H-10407 although the serum did not possess bactericidal activity. The anti-colonization factor serum did not agglutinate a strain of E. coli K-12 possessing the K88 colonization factor peculiar to E. coli enterotoxigenic for swine. By electron microscopy it was demonstrated that E. coli H-10407, but not H10407-, possessed pilus-like surface structures which agglutinated with the specific adsorbed (anti-colonization factor) antiserum. E. coli H-10407 possessed three species of plasmid deoxyribonucleic acid, measuring 60 X 10(6), 42 X 10(6), and 3.7 X 10(6) daltons, respectively. E. coli H-10407-P possessed only the 42 X 10(6)- and the 3.7 X 10(6)-dalton plasmid species. Spontaneous loss of the specific H-10407 surface-associated antigen was accompanied by loss of the 60 X 10(6)-dalton species of plasmid deoxyribonucleic acid and loss of colonizing ability. Thus, it is concluded that the E. coli colonization factor described here is a virulence factor which may play an important and possibly essential role in naturally occurring E. coli enterotoxic diarrhea in man. Images PMID:1100526

Plasmid-controlled colonization factor associated with virulence in Esherichia coli enterotoxigenic for humans.

PubMed

Evans, D G; Silver, R P; Evans, D J; Chase, D G; Gorbach, S L

1975-09-01

An enterotoxin-producing strain of Escherichia coli isolated from a case of cholera-like diarrhea (E. coli strain H-10407) was found to possess a surface-associated colonization factor. Colonization was manifested as the ability of small inocula (10(5) bacteria) to attain large (10(9)) populations in the infant rabbit intestine with a concomitant diarrheal response. A laboratory-passed derivative of E. coli H-10407, designated H-10407-P, failed to exhibit an increase in population in the infant rabbit and also failed to induce diarrhea. Cell-free culture supernatant fluids of E. coli H-10407 and H-10407-P produced equivalent enterotoxic responses in infant and in adult rabbits. Specific anti-colonization factor antiserum was produced by adsorbing hyperimmune anti-H-10407 serum with both heat-killed and living cells E. coli H-10407-P. This specific adsorbed serum protected infant rabbits from challenge with living E. coli H-10407 although the serum did not possess bactericidal activity. The anti-colonization factor serum did not agglutinate a strain of E. coli K-12 possessing the K88 colonization factor peculiar to E. coli enterotoxigenic for swine. By electron microscopy it was demonstrated that E. coli H-10407, but not H10407-, possessed pilus-like surface structures which agglutinated with the specific adsorbed (anti-colonization factor) antiserum. E. coli H-10407 possessed three species of plasmid deoxyribonucleic acid, measuring 60 X 10(6), 42 X 10(6), and 3.7 X 10(6) daltons, respectively. E. coli H-10407-P possessed only the 42 X 10(6)- and the 3.7 X 10(6)-dalton plasmid species. Spontaneous loss of the specific H-10407 surface-associated antigen was accompanied by loss of the 60 X 10(6)-dalton species of plasmid deoxyribonucleic acid and loss of colonizing ability. Thus, it is concluded that the E. coli colonization factor described here is a virulence factor which may play an important and possibly essential role in naturally occurring E. coli enterotoxic diarrhea in man.

Risk factors and outcomes of organ-space surgical site infections after elective colon and rectal surgery.

PubMed

Gomila, Aina; Carratalà, Jordi; Camprubí, Daniel; Shaw, Evelyn; Badia, Josep Mª; Cruz, Antoni; Aguilar, Francesc; Nicolás, Carmen; Marrón, Anna; Mora, Laura; Perez, Rafel; Martin, Lydia; Vázquez, Rosa; Lopez, Ana Felisa; Limón, Enric; Gudiol, Francesc; Pujol, Miquel

2017-01-01

Organ-space surgical site infections (SSI) are the most serious and costly infections after colorectal surgery. Most previous studies of risk factors for SSI have analysed colon and rectal procedures together. The aim of the study was to determine whether colon and rectal procedures have different risk factors and outcomes for organ-space SSI. A multicentre observational prospective cohort study of adults undergoing elective colon and rectal procedures at 10 Spanish hospitals from 2011 to 2014. Patients were followed up until 30 days post-surgery. Surgical site infection was defined according to the Centers for Disease Control and Prevention criteria. Oral antibiotic prophylaxis (OAP) was considered as the administration of oral antibiotics the day before surgery combined with systemic intravenous antibiotic prophylaxis. Of 3,701 patients, 2,518 (68%) underwent colon surgery and 1,183 (32%) rectal surgery. In colon surgery, the overall SSI rate was 16.4% and the organ-space SSI rate was 7.9%, while in rectal surgery the rates were 21.6% and 11.5% respectively ( p  < 0.001). Independent risk factors for organ-space SSI in colon surgery were male sex (Odds ratio -OR-: 1.57, 95% CI: 1.14-2.15) and ostomy creation (OR: 2.65, 95% CI: 1.8-3.92) while laparoscopy (OR: 0.5, 95% CI: 0.38-0.69) and OAP combined with intravenous antibiotic prophylaxis (OR: 0.7, 95% CI: 0.51-0.97) were protective factors. In rectal surgery, independent risk factors for organ-space SSI were male sex (OR: 2.11, 95% CI: 1.34-3.31) and longer surgery (OR: 1.49, 95% CI: 1.03-2.15), whereas OAP with intravenous antibiotic prophylaxis (OR: 0.49, 95% CI: 0.32-0.73) was a protective factor. Among patients with organ-space SSI, we found a significant difference in the overall 30-day mortality, being higher in colon surgery than in rectal surgery (11.5% vs 5.1%, p  = 0.04). Organ-space SSI in colon and rectal surgery has some differences in terms of incidence, risk factors and outcomes. These differences could be considered for surveillance purposes and for the implementation of preventive strategies. Administration of OAP would be an important measure to reduce the OS-SSI rate in both colon and rectal surgeries.

Colon cancer cells adopt an invasive phenotype without mesenchymal transition in 3-D but not 2-D culture upon combined stimulation with EGF and crypt growth factors.

PubMed

Ludwig, Kirsten; Tse, Edison S; Wang, Jean Yj

2013-05-02

The intestinal crypt homeostasis is maintained by a combination of growth factors including Wnt, R-Spondin1, Noggin and the epidermal growth factor (EGF). In human colorectal cancer, the Wnt pathway is constitutively activated through genetic and epigenetic alterations in as many as 11 genes encoding components of this crypt stem-cell maintenance mechanism. Although the proliferation of colon cancer cells does not require Wnt, it is possible that colon cancer cells can still respond to the crypt growth factors in the colonic microenvironment. A number of studies have shown that epithelial cells behave differently in 3-D versus 2-D cultures. Because the 3-D conditions more closely mimic the in vivo environment, we examined the effects of Wnt and other crypt growth factors on colon cancer cell growth in 3-D culture. Colon cancer cells were grown in 3-D matrigel supplemented with different combinations of crypt growth factors and colonies were examined for morphology and pathways. When colon cancer cells were cultured in 3-D with EGF, they grew as round spheroid colonies. However, colon cancer cells also grew as flat, disc-like colonies when cultured with EGF plus Wnt, R-Spondin1 and Noggin. Disc colonies were found to have comparable levels of E-cadherin as the spheroid colonies, but showed decreased E-cadherin at the cell-matrix contact sites. Disc colonies also elaborated F-actin rich protrusions (FRP) at the cell-matrix edge, reminiscent of an invasive phenotype but without the expression of vimentin. These E-cadherin and F-actin alterations were not induced by the four growth factors in 2-D culture. Formation of the disc colonies was inhibited by the knockdown of β-catenin and by protein kinase inhibitors such as gefitinib, imatinib and MK-2206. Furthermore, withdrawal of the crypt growth factors was able to revert the disc colonies to spheroid growth, showing that the invasive phenotype was reversible dependent on the availability of growth factors. These findings show that colon cancer cells remain responsive to the growth factors in the crypt microenvironment and can be induced to undergo morphological transformation in the more physiologically relevant 3-D culture.

Using Project-Based Learning and Google Docs to Support Diversity

ERIC Educational Resources Information Center

Leh, Amy

2014-01-01

A graduate course, ETEC543 ("Technology and Learning I"), was revised to better serve increasing new student population, international students, in an academic program. Project-based learning, Google Docs, and instructional strategies fostering diversity and critical thinking were incorporated into the course redesign. Observations,…

High susceptibility prevalence for F4+ and F18+Escherichia coli in Flemish pigs.

PubMed

Nguyen, Ut V; Coddens, Annelies; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Poucke, Mario Van; Peelman, Luc; Cox, Eric

2017-04-01

F4 and/or F18 enterotoxigenic Escherichia coli (F4 + /F18 + ETEC) are responsible for diarrhea while F18 + verotoxigenic E. coli (F18 + VTEC) cause edema disease in pigs. Both infections can result in severe economic losses, which are mainly the result of the medication, growth retardation and mortality. The susceptibility of piglets to these pathogens is determined by the presence of F4 and F18 receptors (F4R and F18R). Understanding the composition of the susceptibility phenotypes of pigs is useful for animal health and breeding management. This study aimed to determine the prevalence of the F4 ETEC susceptibility phenotypes and F18 + E. coli susceptibility among Flemish pig breeds by using the in vitro villous adhesion assay. In this study, seven F4 ETEC susceptibility phenotypes were found, namely A (F4 ab R + , ac R + , ad R + ; 59.16%), B (F4 ab R + , ac R + , ad R - ; 6.28%), C (F4 ab R + , ac R - , ad R + ; 2.62%), D (F4 ab R - , ac R - , ad R + ; 6.28%), E (F4 ab R - , ac R - , ad R - ; 24.08%), F (F4 ab R + , ac R - , ad R - ; 1.05%) and G (F4 ab R - , ac R + , ad R - ; 0.52%). F4ab and F4ac E. coli showed a stronger degree of adhesion to the intestinal villi (53.40% and 52.88% strong adhesion, respectively), compared to F4ad E. coli (43.46% strong adhesion). Furthermore, the correlation between F4ac and F4ab adhesion was higher (r=0.78) than between F4ac and F4ad adhesion (r=0.41) and between F4ab and F4ad adhesion (r=0.57). For F18 + E. coli susceptibility, seven out of 82 pigs were F18R negative (8.54%), but only two of these seven pigs (2.44%) were also negative for F4R. As such, the chance to identify a pig that is positive for a F4 ETEC variant or F18 + E. coli is 97.56%. Therefore, significant economic losses will arise due to F4 + and/or F18 + E. coli infections in the Flemish pig population due to the high susceptibility prevalence. Copyright © 2016 Elsevier B.V. All rights reserved.

Isolation and Characterization of Lytic Phage vB_EcoM_JS09 against Clinically Isolated Antibiotic-Resistant Avian Pathogenic Escherichia coli and Enterotoxigenic Escherichia coli.

PubMed

Zhou, Yan; Bao, Hongduo; Zhang, Hui; Wang, Ran

2015-01-01

To characterize the lytic coliphage vB_EcoM_JS09 (phage JS09) isolated from sewage samples of a swine farm in Jiangsu Province, China, which infects antibiotic-resistant avian pathogenic Escherichia coli (APEC) and enterotoxigenic E. coli (ETEC). Transmission electron microscopy revealed that phage JS09 has an isometric icosahedral head (76 nm in diameter) and a long contractile tail (140 nm in length) and features a T-even morphology. Its latent period was 30 min and the average burst size was 79 phage particles per infected cell. It attached to the host cells within 9 min. JS09 could infect 16 clinically isolated APEC and ETEC strains and the laboratory-engineered E. coli K and B strains. Ten of the clinical isolates of E. coli were resistant to antibiotics. At a multiplicity of infection of 10, 3, 1, or 0.3, the phage caused rapid cell lysis within 2 h, resulting in 5- to 10-fold reductions in cell concentration. Sequencing of the JS09 genome revealed a 169.148-kb linear but circularly permuted and terminally redundant dsDNA with 37.98% G+C content. Two hundred seventy-three open reading frames were predicted to be coding sequences, 135 of which were functionally defined and organized in a modular format which includes modules for DNA replication, DNA packaging, structural proteins, and host cell lysis proteins. Phage JS09 is assigned to the Caudovirales order (Myoviridae phage family), and it is considered a T4-like phage based on its morphological, genomic, and growth characteristics. JS09 gp37, a receptor-binding protein (RBP) important for host cell infection, shares little homology with other RBP in the NCBI database, which suggests that the variable regions in gp37 determine the unique host range of phage JS09. Protein sequence comparisons cluster the putative 'RBP' of JS09 much more closely with those of Yersinia phage phiD1, phage TuIa, and phage TuIb. A novel lytic coliphage named JS09 was isolated from sewage samples of a swine farm in Jiangsu Province, China. It could infect antibiotic-resistant APEC and ETEC. The morphological, genomic, and growth characteristics of JS09 were studied, and this will be helpful for phage therapy in controlling diseases caused by APEC and ETEC. © 2015 S. Karger AG, Basel.

Murine Vaginal Colonization Model for Investigating Asymptomatic Mucosal Carriage of Streptococcus pyogenes

PubMed Central

Watson, Michael E.; Nielsen, Hailyn V.; Hultgren, Scott J.

2013-01-01

While many virulence factors promoting Streptococcus pyogenes invasive disease have been described, specific streptococcal factors and host properties influencing asymptomatic mucosal carriage remain uncertain. To address the need for a refined model of prolonged S. pyogenes asymptomatic mucosal colonization, we have adapted a preestrogenized murine vaginal colonization model for S. pyogenes. In this model, derivatives of strains HSC5, SF370, JRS4, NZ131, and MEW123 established a reproducible, asymptomatic colonization of the vaginal mucosa over a period of typically 3 to 4 weeks' duration at a relatively high colonization efficiency. Prior treatment with estradiol prolonged streptococcal colonization and was associated with reduced inflammation in the colonized vaginal epithelium as well as a decreased leukocyte presence in vaginal fluid compared to the levels of inflammation and leukocyte presence in non-estradiol-treated control mice. The utility of our model for investigating S. pyogenes factors contributing to mucosal carriage was verified, as a mutant with a mutation in the transcriptional regulator catabolite control protein A (CcpA) demonstrated significant impairment in vaginal colonization. An assessment of in vivo transcriptional activity in the CcpA− strain for several known CcpA-regulated genes identified significantly elevated transcription of lactate oxidase (lctO) correlating with excessive generation of hydrogen peroxide to self-lethal levels. Deletion of lctO did not impair colonization, but deletion of lctO in a CcpA− strain prolonged carriage, exceeding even that of the wild-type strain. Thus, while LctO is not essential for vaginal colonization, its dysregulation is deleterious, highlighting the critical role of CcpA in promoting mucosal colonization. The vaginal colonization model should prove effective for future analyses of S. pyogenes mucosal colonization. PMID:23460515

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors.

PubMed

Schwarz, Carsten; Brandt, Claudia; Antweiler, Elisabeth; Krannich, Alexander; Staab, Doris; Schmitt-Grohé, Sabina; Fischer, Rainald; Hartl, Dominik; Thronicke, Anja; Tintelnot, Kathrin

2017-01-01

An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Clinical, microbiological and laboratory data of 161 patients aged 6-59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13-32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955-0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009-0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873-98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518-93.0705, p<0.05). Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp.

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors

PubMed Central

Schwarz, Carsten; Brandt, Claudia; Antweiler, Elisabeth; Krannich, Alexander; Staab, Doris; Schmitt-Grohé, Sabina; Fischer, Rainald; Hartl, Dominik

2017-01-01

Background An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Material and methods Clinical, microbiological and laboratory data of 161 patients aged 6–59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Results Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13–32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955–0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009–0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873–98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518–93.0705, p<0.05). Conclusion Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp. PMID:28178337

Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia.

PubMed

Tan, Xiaojiang; Zhu, Song; Yan, Dongxing; Chen, Weiping; Chen, Ruilan; Zou, Jian; Yan, Jingdong; Zhang, Xiangdong; Farmakiotis, Dimitrios; Mylonakis, Eleftherios

2016-08-01

This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for ≥48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for ≥7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23% vs 15%, P=.01 and 34% vs. 15%, P<.001 in propensity score-matched subgroups). Administration of antifungal agents was not associated with A. baumannii VAP (29% vs. 21%, P=.153) but with higher in-hospital mortality (53% vs. 39%, P=.037). Candida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prevalence and risk factors for Staphylococcus aureus colonization in individuals entering maximum-security prisons.

PubMed

Mukherjee, D V; Herzig, C T A; Jeon, C Y; Lee, C J; Apa, Z L; Genovese, M; Gage, D; Koenigsmann, C J; Lowy, F D; Larson, E L

2014-03-01

To assess the prevalence and risk factors for colonization with Staphylococcus aureus in inmates entering two maximum-security prisons in New York State, USA, inmates (N=830) were interviewed and anterior nares and oropharyngeal samples collected. Isolates were characterized using spa typing. Overall, 50·5% of women and 58·3% of men were colonized with S. aureus and 10·6% of women and 5·9% of men were colonized with MRSA at either or both body sites. Of MSSA isolates, the major subtypes were spa type 008 and 002. Overall, risk factors for S. aureus colonization varied by gender and were only found in women and included younger age, fair/poor self-reported general health, and longer length of prior incarceration. Prevalence of MRSA colonization was 8·2%, nearly 10 times greater than in the general population. Control of epidemic S. aureus in prisons should consider the constant introduction of strains by new inmates.

Efficacy and safety of a patch vaccine containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase 3, randomised, double-blind, placebo-controlled field trial in travellers from Europe to Mexico and Guatemala.

PubMed

Behrens, Ronald H; Cramer, Jakob P; Jelinek, Tomas; Shaw, Hilary; von Sonnenburg, Frank; Wilbraham, Darren; Weinke, Thomas; Bell, David J; Asturias, Edwin; Pauwells, Hermann L Enkerlin; Maxwell, Roberto; Paredes-Paredes, Mercedes; Glenn, Gregory M; Dewasthaly, Shailesh; Stablein, Donald M; Jiang, Zhi-Dong; DuPont, Herbert L

2014-03-01

Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the efficacy and safety of a skin-patch vaccine containing the pathogen's heat-labile toxin (LT) in a population of travellers to Mexico and Guatemala. In this phase 3, randomised, double-blind, placebo-controlled field trial, healthy adults (aged 18-64 years) travelling from Germany or the UK to Mexico or Guatemala were assigned in a 1:1 ratio by a dynamic electronic randomisation system to receive transcutaneous immunisation with a patch containing 37.5 μg of ETEC LT or a placebo patch. Participants, site staff, and the investigators who did the analyses were masked to group assignment. Participants were vaccinated before travel, with two patches given 14 days apart. In the destination country, participants tracked stool output in a diary and provided stool samples for pathogen identification if diarrhoea occurred. The primary endpoint was the proportion of participants with at least one episode of moderate-to-severe diarrhoea (defined as four or more unformed stools in a 24 h period) in which either or both ETEC enterotoxins (LT and heat-stable toxin [ST]) were detected. The study is registered at ClinicalTrials.gov, number NCT00993681. 2036 participants were recruited and randomly assigned between Oct 14, 2009, and Aug 13, 2010, with 1016 allocated to receive the LT patch and 1020 the placebo patch. 821 participants in the LT-patch group and 823 in the placebo group received both vaccinations and were analysed in the per-protocol population. 30 (3.7%, 95% CI 2.5-5.2) participants in the LT-patch group and 46 (5.6%, 4.1-7.4) in the placebo group had moderate or severe ETEC diarrhoea (vaccine efficacy 34.6%, -2.2 to 58.9; p=0.0621). 9333 local (ie, patch-site) adverse events (including erythema, rash, pruritus, hyperpigmentation, pain, hypopigmentation, and oedema) occurred in 943 (93%) of 1015 participants in the LT-patch group, compared with 1444 local adverse events in 574 (56%) of 1019 participants in the placebo group (p<0.0001). Serious adverse events occurred in 25 participants (14 in the LT-patch group and 11 in the placebo group), with all regarded as either unrelated or possibly related to treatment. Vaccine-induced hyperpigmentation persisted for at least 180 days after vaccination in 150 (18%) of the 849 participants who received both vaccinations and returned for final assessment in the LT-patch group, compared with none of the 842 participants in the placebo group. The vaccine was immunogenic, with a post-vaccination geometric mean titre of LT-specific serum immunoglobulin G of 3400.29, compared with 315.41 in the placebo group. Although the LT antigen was delivered effectively by the skin patch, the vaccine did not protect travellers against diarrhoea caused by ETEC or other organisms. Future vaccines against travellers' diarrhoea might need to include several antigens against various diarrhoeal pathogens, and might need to be able to generate mucosal and higher systemic immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Morbidity predicting factors of penetrating colon injuries.

PubMed

Mickevicius, A; Valeikaite, G; Tamelis, A; Saladzinskas, Z; Svagzdys, S; Pavalkis, D

2010-01-01

To analyze patients suffering from penetrating colon injuries management, clinical outcomes and factors, which predict higher morbidity and complications rate. this was a retrospective analysis of prospectively collected data from patients with injured colon from 1995 to 2008. Age, time till operation, systolic blood pressure, part of injured colon, fecal contamination, PATI were registered. Monovariate and multivariate logistic regression was performed to determine higher morbidity predictive factors. 61 patients had penetrating colon injuries. Major fecal contamination of the peritoneal cavity and systolic blood pressure lower than 90 mmHg are independent factors determining the fecal diversion operation. Primary repair group analysis establish that major fecal contamination and systolic blood pressure lower than 90 mmHg OR = 4.2 and 0.96 were significant risk factors, which have contributed to the development of postoperative complications. And systolic blood pressure lower than 90 mmHg and PATI 20 predict OR = 0.05 and 2.61 higher morbidity. Fecal contamination of the peritoneal cavity and hypotension were determined to be crucial in choice of performing fecal diversion or primary repair. But the same criteria and PATI predict higher rate of postoperative complications and higher morbidity.

A Nasal Epithelial Receptor for Staphylococcus aureus WTA Governs Adhesion to Epithelial Cells and Modulates Nasal Colonization

PubMed Central

Faulstich, Manuela; Grau, Timo; Severin, Yannik; Unger, Clemens; Hoffmann, Wolfgang H.; Rudel, Thomas; Autenrieth, Ingo B.; Weidenmaier, Christopher

2014-01-01

Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization. PMID:24788600

Colon cancer: personality factors predictive of onset and stage of presentation.

PubMed

Kavan, M G; Engdahl, B E; Kay, S

1995-11-01

This study examined premorbid personality correlates of colon cancer and stage of presentation of colon cancer to health care providers. Sixty-one male veterans who completed the MMPI between 1947 and 1975 and were then diagnosed with colon cancer between 1977 and 1988 were matched with control patients. A 21-factor solution of the MMPI [1] was used to seek potential personality differences between colon cancer cases and their controls in terms of presence of colon cancer and stage of presentation for this disease. A stepwise conditional regression analysis found significant differences between the colon cancer and control groups on the Aggressive Hostility variable (p < 0.018). A multivariate analysis of variance conducted across the stages of colon cancer presentation found that patients who presented later on for colon cancer had higher Phobia scores (p < 0.05). Religious Fundamentalism was also related to presentation (p < 0.05), but in a nonlinear manner. Discussion is related to previous findings regarding the relationship between personality and development of cancer, as well as to implications for patient screening.

Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas

PubMed Central

Sayar, İlyas; Gökçe, Aysun; Demirtas, Levent; Eken, Hüseyin; Çimen, Ferda Keskin; Çimen, Orhan

2017-01-01

Background There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. Material/Methods Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. Results In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. Conclusions Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas. PMID:28561015

Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.

PubMed

Sayar, İlyas; Gökçe, Aysun; Demirtas, Levent; Eken, Hüseyin; Çimen, Ferda Keskin; Çimen, Orhan

2017-05-31

BACKGROUND There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. MATERIAL AND METHODS Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. RESULTS In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. CONCLUSIONS Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas.

Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia.

PubMed

Ford, Clyde D; Lopansri, Bert K; Haydoura, Souha; Snow, Greg; Dascomb, Kristin K; Asch, Julie; Bo Petersen, Finn; Burke, John P

2015-01-01

OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.

Characteristics of right-sided colonic neoplasia and colonoscopy barriers limiting their early detection and prognosis: a review of the literature.

PubMed

Fischbach, Wolfgang; Elsome, Rory; Amlani, Bharat

2018-06-05

Colonoscopy provides less protection from colorectal cancer in the right colon than the left. Areas covered: This review examines patient outcomes and colonoscopy success rates to identify factors that limit the protective effect of colonoscopy in the right colon. The MEDLINE and Embase databases were searched for literature from 2000 onwards, on the long-term outcomes and differences in screening practice between the right and left colon. In total, 12 systematic reviews (including nine meta-analyses) and 44 primary data records were included. Differences in patient outcomes and colonoscopy practice were identified between the right and left colon, suggesting that several factors, many of which disproportionally affect the right colon, impact lesion detection rates. Shorter withdrawal times reduce detection rates, while longer times significantly increase detection; mostly of adenomas in the right colon. Colonoscope attachments often only show a significant improvement in detection rates in the right colon, suggesting detection is more challenging due to visibility of the right colonic mucosa. Higher bowel cleansing grades significantly improve detection rates in the right colon compared to the left. Expert commentary: These findings confirm the need for continued improvement of colonoscopy effectiveness, and obligatory quality assessment, overall and especially in the right colon.

Predictors of Staphylococcus aureus Rectovaginal Colonization in Pregnant Women and Risk for Maternal and Neonatal Infections

PubMed Central

Top, Karina A.; Buet, Amanda; Whittier, Susan; Ratner, Adam J.; Saiman, Lisa

2012-01-01

Background. Staphylococcus aureus infections are increasing among pregnant and postpartum women and neonates, but risk factors for S. aureus colonization in pregnancy and the association between maternal colonization and infant infections are not well defined. We sought to identify risk factors for maternal S. aureus rectovaginal colonization and assess colonization as a risk factor for infections among mothers and infants. Methods. We conducted a retrospective cohort study of pregnant women and their infants. Demographic and clinical data, including S. aureus infections that occurred in mothers from 3 months before to 3 months after delivery and in infants during the first 3 months of life, were extracted from electronic medical records. Predictors for maternal S. aureus rectovaginal colonization were assessed through multivariable logistic regression analysis. Results. The cohort included 2702 women and 2789 infants. The prevalence of maternal rectovaginal colonization with methicillin-susceptible S. aureus and methicillin-resistant S. aureus (MRSA) was 13% and 0.7%. Independent predictors of colonization included multigravidity, human immunodeficiency virus seropositivity, and group B Streptococcus colonization. S. aureus colonization was associated with an increased risk of infection in mothers (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.4–8.8) but not in their infants (OR, 1.9; 95% CI, .6–5.6). The frequency of S. aureus infections was 0.8% in mothers and 0.7% in infants. Conclusions. S. aureus rectovaginal colonization was associated with an increased risk of infections in women but not in their infants. The frequency of MRSA infections was low. These data suggest that routine MRSA screening of pregnant women may not be indicated. PMID:23687569

Prevalence of and risk factors for community-acquired methicillin-resistant and methicillin-sensitive staphylococcus aureus colonization in children seen in a practice-based research network.

PubMed

Fritz, Stephanie A; Garbutt, Jane; Elward, Alexis; Shannon, William; Storch, Gregory A

2008-06-01

We sought to define the prevalence of and risk factors for methicillin-resistant Staphylococcus aureus nasal colonization in the St Louis pediatric population. Children from birth to 18 years of age presenting for sick and well visits were recruited from pediatric practices affiliated with a practice-based research network. Nasal swabs were obtained, and a questionnaire was administered. We enrolled 1300 participants from 11 practices. The prevalence of methicillin-resistant S aureus nasal colonization varied according to practice, from 0% to 9% (mean: 2.6%). The estimated population prevalence of methicillin-resistant S aureus nasal colonization for the 2 main counties of the St Louis metropolitan area was 2.4%. Of the 32 methicillin-resistant S aureus isolates, 9 (28%) were health care-associated types and 21 (66%) were community-acquired types. A significantly greater number of children with community-acquired methicillin-resistant S aureus were black and were enrolled in Medicaid, in comparison with children colonized with health care-associated methicillin-resistant S aureus. Children with both types of methicillin-resistant S aureus colonization had increased contact with health care, compared with children without colonization. Methicillin-sensitive S aureus nasal colonization ranged from 9% to 31% among practices (mean: 24%). The estimated population prevalence of methicillin-sensitive S aureus was 24.6%. Risk factors associated with methicillin-sensitive S aureus colonization included pet ownership, fingernail biting, and sports participation. Methicillin-resistant S aureus colonization is widespread among children in our community and includes strains associated with health care-associated and community-acquired infections.

Risk factors associated with recurrent hemorrhage after the initial improvement of colonic diverticular bleeding.

PubMed

Nishikawa, Hiroki; Maruo, Takanori; Tsumura, Takehiko; Sekikawa, Akira; Kanesaka, Takashi; Osaki, Yukio

2013-03-01

We elucidated risk factors contributing to recurrent hemorrhage after initial improvement of colonic diverticular bleeding. 172 consecutive hospitalized patients diagnosed with colonic diverticular bleeding were analyzed. Recurrent hemorrhage after initial improvement of colonic diverticular bleeding is main outcome measure. We analyzed factors contributing to recurrent hemorrhage risk in univariate and multivariate analyses. The length of the observation period after improvement of colonic diverticular bleeding was 26.4 +/- 14.6 months (range, 1-79 months). The cumulative recurrent hemorrhage rate in all patients at 1 and 2 years was 34.8% and 41.8%, respectively. By univariate analysis, age > 70 years (P = 0.021), BMI > 25 kg/m2 (P = 0.013), the use of anticoagulant drugs (P = 0.034), the use of NSAIDs (P = 0.040), history of hypertension (P = 0.011), history of smoking (P = 0.030) and serum creatinine level > 1.5 mg/dL (P < 0.001) were found to be significant risk factors for recurrent colonic diverticular bleeding. By multivariate analysis, age > 70 years (Hazard ratio (HR), 1.905, 95% confidence interval (CI), 1.067-3.403, P = 0.029), history of hypertension (HR, 0.493, 95% CI, 0.245-0.993, P = 0.048) and serum creatinine level > 1.5 mg/dL (HR, 95% CI, 0.288-0.964, P = 0.044) were shown to be significant independent risk factors. Close observation after the initial improvement of colonic diverticular bleeding is needed, especially in elderly patients or patients with history of hypertension or renal deficiency.

The first 30 years of Shiga toxin-producing Escherichia coli in cattle production: Incidence, preharvest ecology, and management

USDA-ARS?s Scientific Manuscript database

Of the 700 serotypes of Escherichia coli, most are commensal; however, some range from mildly to highly pathogenic and can cause death. The disease-causing enterovirulent E. coli are classified as: Enterotoxigenic E. coli (ETEC), Enteropathogenic E. coli (EPEC), Enteroinvasive E. coli (EIEC), and ...

Medical Surveillance Monthly Report (MSMR). Volume 4, Number 6, September 1998

DTIC Science & Technology

1998-09-01

bacterial pathogens (from both cases and noncases) were Salmonella enteritidis , entero-adherent E. coli (EAEC), entero- toxigenic E. coli (ETEC), and...Isolation rate (% of cultures + for pathogen) No. of cultures + for pathogen Isolation rate (% of cultures + for pathogen) Salmonella enteritidis 32...infections ............. 8 ARD surveillance update .................................................. 13 Foodborne outbreak, Salmonella

Lease of Parcel ED-1 of the Oak Ridge Reservation by the East Tennessee Economic Council

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-04-01

The US Department of Energy (DOE) has completed an environmental assessment (DOE/EA-1113) for the proposed lease of 957.16 acres of the Oak Ridge Reservation (ORR) to the East Tennessee Economic Council (ETEC), a non-profit community organization, for a period of 10 years, with an option for renewal. ETEC proposes to develop an industrial park on the leased site to provide employment opportunities for DOE and contractor employees affected by decreased federal funding. Based on the results of the analysis reported in the EA and implementation of mitigation measures defined in this Finding of No Significant Impact (FONSI), DOE has determinedmore » that the proposed action is not a major Federal action that would significantly affect the quality of the human environment within the context of the National Environmental Policy Act of 1969 (NEPA). Therefore, preparation of an environmental impact statement (EIS) is not necessary, and DOE is issuing this mitigated FONSI. DOE will implement a Mitigation Action Plan for this project and provide annual reports on mitigation and monitoring.« less

Traumatic colon injuries -- factors that influence surgical management.

PubMed

Jinescu, G; Lica, I; Beuran, M

2013-01-01

This study sought to evaluate current trends in surgical management of colon injuries in a level I urban trauma centre, in the light of our increasing confidence in primary repair. Our retrospective study evaluates the results of 116 patients with colon injuries operated at Bucharest Clinical Emergency Hospital, in the light of some of the most commonly cited factors which could influence the surgeon decision-making process towards primary repair or colostomy. Blunt injuries were more common than penetrating injuries (65% vs. 31%). Significant other injuries occurred in 85 (73%) patients. Primary repair was performed in 95 patients (82%). Fecal diversion was used in 21 patients(18%). Multiple factors influence the decision-making process: shock, fecal contamination, associated injuries and higher scores on the Abdominal Trauma Index (ATI) and Colon Injury Scale (CIS). Colon related intra-abdominal complications occurred in 7% of patients in whom the colon injury was closed primarily and in 14% of patients in whom a stoma was created, ATI having a predictive role in their occurrence. The overall mortality rate was 19%. Primary repair of colon injuries, either by primary suture or resection and anastomosis, is a safe method in the management of the majority of colonic injuries. Colostomy is preferred for patients with ATI ≥ 30 and CIS ≥ 4. Surgical judgment remains the final arbiter in decision making. Celsius.

Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneumonia.

PubMed

Ewig, S; Torres, A; El-Ebiary, M; Fábregas, N; Hernández, C; González, J; Nicolás, J M; Soto, L

1999-01-01

We prospectively evaluated the relation of upper airway, lower airway, and gastric colonization patterns with the development of pneumonia and its etiology in 48 patients with surgical (n = 25) and medical (n = 23) head injury. Initial colonization was assessed by cultures of nasal and pharyngeal swabs, tracheobronchial aspirates, gastric juice, and bronchoscopically retrieved protected specimen brush. Follow-up colonization was determined until the end points extubation, suspected ventilator-associated pneumonia (VAP), or death. The initial colonization rate at any site at ICU admission was 39/47 (83%). It mainly accounted for Group I pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae) of the upper and lower airways. At follow-up, colonization rates with Group II pathogens (Gram-negative enteric bacilli and Pseudomonas spp.) increased significantly. The high initial bacterial load with Group I pathogens of the upper airways and trachea decreased during Days 2 to 4, whereas that of Group II pathogens increased. Upper airway colonization was an independent predictor of follow-up tracheobronchial colonization (odds ratio [OR], 9.9; 95% confidence interval [CI], 1.8 to 56.3 for initial colonization with Group I pathogens; OR, 23.9; 95% CI, 3.8 to 153.3 for follow-up colonization with Group II pathogens). Previous (short-term) antibiotics had a protective effect against colonization with Group I pathogens of the lower respiratory tract (OR, 0.2; 95% CI, 0.05 to 0.86), but they were a risk factor for colonization with Group II pathogens (OR, 6.1; 95% CI, 1.3 to 29). Initial tracheobronchial colonization with Group I pathogens was associated with a higher probability of early onset pneumonia (OR, 4. 1; 95% CI, 0.7 to 23.3), whereas prolonged antibiotic treatment (> 24 h) independently predicted late-onset pneumonia (OR, 9.2; 95% CI, 1.7 to 51.3). We conclude that patients with head injury are colonized in the airways mainly by Group I pathogens early in the evolution of illness. The upper airways represent the main reservoir for subsequent lower airway colonization with Group I pathogens. Previous (short-term) antibiotic treatment is protective against initial tracheobronchial colonization with Group I pathogens, but it represents a risk factor for subsequent lower airway colonization by Group II pathogens.

Bacterial Community Profiling of Plastic Litter in the Belgian Part of the North Sea.

PubMed

De Tender, Caroline A; Devriese, Lisa I; Haegeman, Annelies; Maes, Sara; Ruttink, Tom; Dawyndt, Peter

2015-08-18

Bacterial colonization of marine plastic litter (MPL) is known for over four decades. Still, only a few studies on the plastic colonization process and its influencing factors are reported. In this study, seafloor MPL was sampled at different locations across the Belgian part of the North Sea to study bacterial community structure using 16S metabarcoding. These marine plastic bacterial communities were compared with those of sediment and seawater, and resin pellets sampled on the beach, to investigate the origin and uniqueness of plastic bacterial communities. Plastics display great variation of bacterial community composition, while each showed significant differences from those of sediment and seawater, indicating that plastics represent a distinct environmental niche. Various environmental factors correlate with the diversity of MPL bacterial composition across plastics. In addition, intrinsic plastic-related factors such as pigment content may contribute to the differences in bacterial colonization. Furthermore, the differential abundance of known primary and secondary colonizers across the various plastics may indicate different stages of bacterial colonization, and may confound comparisons of free-floating plastics. Our studies provide insights in the factors that shape plastic bacterial colonization and shed light on the possible role of plastic as transport vehicle for bacteria through the aquatic environment.

Performance of five surface energy balance models for estimating daily evapotranspiration in high biomass sorghum

NASA Astrophysics Data System (ADS)

Wagle, Pradeep; Bhattarai, Nishan; Gowda, Prasanna H.; Kakani, Vijaya G.

2017-06-01

Robust evapotranspiration (ET) models are required to predict water usage in a variety of terrestrial ecosystems under different geographical and agrometeorological conditions. As a result, several remote sensing-based surface energy balance (SEB) models have been developed to estimate ET over large regions. However, comparison of the performance of several SEB models at the same site is limited. In addition, none of the SEB models have been evaluated for their ability to predict ET in rain-fed high biomass sorghum grown for biofuel production. In this paper, we evaluated the performance of five widely used single-source SEB models, namely Surface Energy Balance Algorithm for Land (SEBAL), Mapping ET with Internalized Calibration (METRIC), Surface Energy Balance System (SEBS), Simplified Surface Energy Balance Index (S-SEBI), and operational Simplified Surface Energy Balance (SSEBop), for estimating ET over a high biomass sorghum field during the 2012 and 2013 growing seasons. The predicted ET values were compared against eddy covariance (EC) measured ET (ETEC) for 19 cloud-free Landsat image. In general, S-SEBI, SEBAL, and SEBS performed reasonably well for the study period, while METRIC and SSEBop performed poorly. All SEB models substantially overestimated ET under extremely dry conditions as they underestimated sensible heat (H) and overestimated latent heat (LE) fluxes under dry conditions during the partitioning of available energy. METRIC, SEBAL, and SEBS overestimated LE regardless of wet or dry periods. Consequently, predicted seasonal cumulative ET by METRIC, SEBAL, and SEBS were higher than seasonal cumulative ETEC in both seasons. In contrast, S-SEBI and SSEBop substantially underestimated ET under too wet conditions, and predicted seasonal cumulative ET by S-SEBI and SSEBop were lower than seasonal cumulative ETEC in the relatively wetter 2013 growing season. Our results indicate the necessity of inclusion of soil moisture or plant water stress component in SEB models for the improvement of their performance, especially under too dry or wet environments.

Pathotyping of Escherichia coli isolated from community toilet wastewater and stored drinking water in a slum in Bangladesh.

PubMed

Harada, H; Fujimori, Y; Gomi, R; Ahsan, Md N; Fujii, S; Sakai, A; Matsuda, T

2018-06-01

This study investigated the occurrence of Escherichia coli pathotypes in sanitary wastewater and drinking water in a Bangladeshi urban slum and the potential associations between these sources. We examined 621 E. coli isolates from sanitary wastewater and stored drinking water by multiplex PCR and dual-index sequencing, classifying them into eight pathotypes based on 14 virulence genes and additionally evaluating the possession of the human-specific E. coli genetic biomarker H8. The proportions of pathogenic E. coli were significantly different (P < 0·001) between wastewater (18·6%) and drinking water (1·7%). StIb-positive enterotoxigenic E. coli (ETEC) were predominant in wastewater, indicating that people in the site carried ETEC. In contrast, no ETEC was present in drinking water and the proportion of H8-positive isolates was significantly smaller (7·8%) than that in wastewater (16·3%) (P = 0·001). Our findings indicate that sanitary wastewater from the slum was heavily contaminated with pathogenic E. coli, posing a great health risk. Furthermore, E. coli contamination of drinking water could be derived from not only human but also other sources. Sanitary wastewater from an urban slum was heavily contaminated with pathogenic Escherichia coli. It is worth noting a great health risk of accidental exposure to pathogenically contaminated wastewater improperly discharged in and around urban slums. The distinct difference in pathotypes between wastewater and drinking water and the significantly smaller positive proportion of the human-specific E. coli genetic biomarker (H8) in drinking water indicate that drinking water contamination could be derived from not only human but also other sources. This highlights that pathotyping in association with the H8 marker provides an indication of pathogen contamination sources of environmental transmission media. © 2018 The Society for Applied Microbiology.

Characterization of Heat-Stable (STa) Toxoids of Enterotoxigenic Escherichia coli Fused to Double Mutant Heat-Labile Toxin Peptide in Inducing Neutralizing Anti-STa Antibodies

PubMed Central

Ruan, Xiaosai; Robertson, Donald C.; Nataro, James P.; Clements, John D.

2014-01-01

A long-standing challenge in developing vaccines against enterotoxigenic Escherichia coli (ETEC), the most common bacteria causing diarrhea in children of developing countries and travelers to these countries, is to protect against heat-stable toxin type Ib (STa or hSTa). STa and heat-labile toxin (LT) are virulence determinants in ETEC diarrhea. LT antigens are often used in vaccine development, but STa has not been included because of its poor immunogenicity and potent toxicity. Toxic STa is not safe for vaccines, but only STa possessing toxicity is believed to be able to induce neutralizing antibodies. However, recent studies demonstrated that nontoxic STa derivatives (toxoids), after being fused to an LT protein, induced neutralizing antibodies and suggested that different STa toxoids fused to an LT protein might exhibit different STa antigenic propensity. In this study, we selected 14 STa toxoids from a mini-STa toxoid library based on toxicity reduction and reactivity to anti-native STa antibodies, and genetically fused each toxoid to a monomeric double mutant LT (dmLT) peptide for 14 STa-toxoid-dmLT toxoid fusions. These toxoid fusions were used to immunize mice and were characterized for induction of anti-STa antibody response. The results showed that different STa toxoids (in fusions) varied greatly in anti-STa antigenicity. Among them, STaN12S, STaN12T, and STaA14H were the top toxoids in inducing anti-STa antibodies. In vitro neutralization assays indicated that antibodies induced by the 3×STaN12S-dmLT fusion antigen exhibited the greatest neutralizing activity against STa toxin. These results suggested 3×STaN12S-dmLT is a preferred fusion antigen to induce an anti-STa antibody response and provided long-awaited information for effective ETEC vaccine development. PMID:24549325

Presence and correlation of some enteric indicator bacteria, diarrheagenic Escherichia coli pathotypes, and Salmonella serotypes in alfalfa sprouts from local retail markets in Pachuca, Mexico.

PubMed

Rangel-Vargas, Esmeralda; Gómez-Aldapa, Carlos A; Torres-Vitela, M Del Refugio; Villarruel-López, Angélica; Gordillo-Martínez, Alberto J; Castro-Rosas, Javier

2015-03-01

Data on the presence of diarrheagenic Escherichia coli pathotypes (DEPs) in alfalfa sprouts and correlations between the presence of coliform bacteria (CB), fecal coliforms (FC), E. coli, DEPs, and Salmonella in alfalfa sprouts are not available. The presence of and correlations between CB, FC, E. coli, DEPs, and Salmonella in alfalfa sprouts were determined. One hundred sprout samples were collected from retail markets in Pachuca, Hidalgo State, Mexico. The presence of indicator bacteria and Salmonella was determined using conventional culture procedures. DEPs were identified using two multiplex PCR procedures. One hundred percent of samples were positive for CB, 90% for FC, 84% for E. coli, 10% for DEPs, and 4% for Salmonella. The populations of CB ranged from 6.2 up to 8.6 log CFU/g. The FC and E. coli concentrations were between , 3 and 1,100 most probable number (MPN)/g. The DEPs identified included enterotoxigenic E. coli (ETEC; 2%), enteropathogenic E. coli (EPEC; 3%), and Shiga toxin-producing E. coli (STEC; 5%). No E. coli O157:H7 strains were detected in any STEC-positive samples. In samples positive for DEPs, the concentrations ranged from 210 to 240 MPN/g for ETEC, 28 to 1,100 MPN/g for EPEC, and 3.6 to 460 MPN/g for STEC. The Salmonella isolates identified included Salmonella enterica serotype Typhimurium in three samples and Salmonella enterica serotype Enteritidis in one. STEC and Salmonella Typhimurium were identified together in one sample. Positive correlations were observed between FC and E. coli, between FC and DEPs, and between E. coli and DEPs. Negative correlations occurred between CB and DEPs and between CB and Salmonella. Neither FC nor E. coli correlated with Salmonella in the sprout samples. To our knowledge, this is the first report of ETEC, EPEC, and STEC isolated from alfalfa sprouts and the first report of correlations between different indicator groups versus DEPs and Salmonella.

Aspergillus Colonization of the Lung Allograft is a Risk Factor for Bronchiolitis Obliterans Syndrome

PubMed Central

Weigt, S. Samuel; Elashoff, Robert M.; Huang, Cathy; Ardehali, Abbas; Gregson, Aric L.; Kubak, Bernard; Fishbein, Michael C.; Saggar, Rajeev; Keane, Michael P.; Saggar, Rajan; Lynch, Joseph P.; Zisman, David A.; Ross, David J.; Belperio, John A.

2014-01-01

Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between 1/2000 and 6/2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87 to 520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS. PMID:19459819

Specific Behaviors Predict Staphylococcus aureus Colonization and Skin and Soft Tissue Infections Among Human Immunodeficiency Virus-Infected Persons

PubMed Central

Crum-Cianflone, Nancy F.; Wang, Xun; Weintrob, Amy; Lalani, Tahaniyat; Bavaro, Mary; Okulicz, Jason F.; Mende, Katrin; Ellis, Michael; Agan, Brian K.

2015-01-01

Background. Few data exist on the incidence and risk factors of Staphylococcus aureus colonization and skin and soft tissue infections (SSTIs) among patients infected with human immunodeficiency virus (HIV). Methods. Over a 2-year period, we prospectively evaluated adults infected with HIV for incident S aureus colonization at 5 body sites and SSTIs. Cox proportional hazard models using time-updated covariates were performed. Results. Three hundred twenty-two participants had a median age of 42 years (interquartile range, 32–49), an HIV duration of 9.4 years (2.7–17.4), and 58% were on highly active antiretroviral therapy (HAART). Overall, 102 patients (32%) became colonized with S aureus with an incidence rate of 20.6 (95% confidence interval [CI], 16.8–25.0) per 100 person-years [PYs]. Predictors of colonization in the final multivariable model included illicit drug use (hazard ratios [HR], 4.26; 95% CI, 1.33–13.69) and public gym use (HR 1.66, 95% CI, 1.04–2.66), whereas antibacterial soap use was protective (HR, 0.50; 95% CI, 0.32–0.78). In a separate model, perigenital colonization was associated with recent syphilis infection (HR, 4.63; 95% CI, 1.01–21.42). Fifteen percent of participants developed an SSTI (incidence rate of 9.4 cases [95% CI, 6.8–12.7] per 100 PYs). Risk factors for an SSTI included incident S aureus colonization (HR 2.52; 95% CI, 1.35–4.69), public shower use (HR, 2.59; 95% CI, 1.48–4.56), and hospitalization (HR 3.54; 95% CI, 1.67–7.53). The perigenital location for S aureus colonization was predictive of SSTIs. Human immunodeficiency virus-related factors (CD4 count, HIV RNA level, and HAART) were not associated with colonization or SSTIs. Conclusions. Specific behaviors, but not HIV-related factors, are predictors of colonization and SSTIs. Behavioral modifications may be the most important strategies in preventing S aureus colonization and SSTIs among persons infected with HIV. PMID:26380335

Aqueous synthesis of ZnTe/dendrimer nanocomposites and their antimicrobial activity: implications in therapeutics

NASA Astrophysics Data System (ADS)

Ghosh, S.; Ghosh, D.; Bag, P. K.; Bhattacharya, S. C.; Saha, A.

2011-03-01

The present strategy proposes a simple and single step aqueous route for synthesizing stable, fluorescent ZnTe/dendrimer nanocomposites with varying dendrimer terminal groups. In these hybrid materials, the fluorescence of the semiconductor combines with the biomimetic properties of the dendrimer making them suitable for various biomedical applications. The ZnTe nanocomposites thus obtained demonstrate bactericidal activity against enteropathogenic bacteria without having toxic effects on the human erythrocytes. The average size of the ZnTe nanoparticles within the dendrimer matrix was in the range of 2.9-6.0 nm, and they have a good degree of crystallinity with a hexagonal crystal phase. The antibacterial activities of the ZnTe/dendrimer nanocomposites (ZnTe DNCs) as well other semiconductor nanocomposites were evaluated against enteropathogenic bacteria including multi-drug resistant Vibrio cholerae serogroup O1 and enterotoxigenic Escherichia coli (ETEC). ZnTe DNCs had significant antibacterial activity against strains of V. cholerae and ETEC with minimum inhibitory concentrations ranging from 64 to 512 μg ml-1 and minimum bactericidal concentrations ranging from 128 to 1000 μg ml-1. Thus, the observed results suggest that these water-soluble active nanocomposites have potential for the treatment of enteric diseases like diarrhoea and cholera.The present strategy proposes a simple and single step aqueous route for synthesizing stable, fluorescent ZnTe/dendrimer nanocomposites with varying dendrimer terminal groups. In these hybrid materials, the fluorescence of the semiconductor combines with the biomimetic properties of the dendrimer making them suitable for various biomedical applications. The ZnTe nanocomposites thus obtained demonstrate bactericidal activity against enteropathogenic bacteria without having toxic effects on the human erythrocytes. The average size of the ZnTe nanoparticles within the dendrimer matrix was in the range of 2.9-6.0 nm, and they have a good degree of crystallinity with a hexagonal crystal phase. The antibacterial activities of the ZnTe/dendrimer nanocomposites (ZnTe DNCs) as well other semiconductor nanocomposites were evaluated against enteropathogenic bacteria including multi-drug resistant Vibrio cholerae serogroup O1 and enterotoxigenic Escherichia coli (ETEC). ZnTe DNCs had significant antibacterial activity against strains of V. cholerae and ETEC with minimum inhibitory concentrations ranging from 64 to 512 μg ml-1 and minimum bactericidal concentrations ranging from 128 to 1000 μg ml-1. Thus, the observed results suggest that these water-soluble active nanocomposites have potential for the treatment of enteric diseases like diarrhoea and cholera. Electronic supplementary information (ESI) available: Dynamic light scattering, atomic force microscopy and hemolytic activity of the nanocomposites. See DOI: 10.1039/c0nr00610f

Insights into Vibrio cholerae Intestinal Colonization from Monitoring Fluorescently Labeled Bacteria

PubMed Central

Millet, Yves A.; Alvarez, David; Ringgaard, Simon; von Andrian, Ulrich H.; Davis, Brigid M.; Waldor, Matthew K.

2014-01-01

Vibrio cholerae, the agent of cholera, is a motile non-invasive pathogen that colonizes the small intestine (SI). Most of our knowledge of the processes required for V. cholerae intestinal colonization is derived from enumeration of wt and mutant V. cholerae recovered from orogastrically infected infant mice. There is limited knowledge of the distribution of V. cholerae within the SI, particularly its localization along the villous axis, or of the bacterial and host factors that account for this distribution. Here, using confocal and intravital two-photon microscopy to monitor the localization of fluorescently tagged V. cholerae strains, we uncovered unexpected and previously unrecognized features of V. cholerae intestinal colonization. Direct visualization of the pathogen within the intestine revealed that the majority of V. cholerae microcolonies attached to the intestinal epithelium arise from single cells, and that there are notable regiospecific aspects to V. cholerae localization and factors required for colonization. In the proximal SI, V. cholerae reside exclusively within the developing intestinal crypts, but they are not restricted to the crypts in the more distal SI. Unexpectedly, V. cholerae motility proved to be a regiospecific colonization factor that is critical for colonization of the proximal, but not the distal, SI. Furthermore, neither motility nor chemotaxis were required for proper V. cholerae distribution along the villous axis or in crypts, suggesting that yet undefined processes enable the pathogen to find its niches outside the intestinal lumen. Finally, our observations suggest that host mucins are a key factor limiting V. cholerae intestinal colonization, particularly in the proximal SI where there appears to be a more abundant mucus layer. Collectively, our findings demonstrate the potent capacity of direct pathogen visualization during infection to deepen our understanding of host pathogen interactions. PMID:25275396

Risk Factors for the Development of Gastrointestinal Colonization With Fluoroquinolone-Resistant Escherichia coli in Residents of Long-Term Care Facilities

PubMed Central

Han, Jennifer H.; Maslow, Joel; Han, Xiaoyan; Xie, Sharon X.; Tolomeo, Pam; Santana, Evelyn; Carson, Lesley; Lautenbach, Ebbing

2014-01-01

Background. The objective of this study was to assess risk factors for the development of fluoroquinolone (FQ)–resistant Escherichia coli gastrointestinal tract colonization in long-term care facility (LTCF) residents. Methods. A prospective cohort study was conducted from 2006 to 2008 at 3 LTCFs. Residents initially colonized with FQ-susceptible E. coli were followed by means of serial fecal sampling for new FQ-resistant E. coli colonization for up to 12 months or until discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQ-resistant E. coli colonization, with antibiotic and device exposures modeled as time-varying covariates. Results. Fifty-seven (47.5%) of 120 residents became newly colonized with FQ-resistant E. coli, with a median time to colonization of 57 days. Fecal incontinence (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.04–3.06; P = .04) was significantly associated with FQ-resistant E. coli acquisition. Receipt of amoxicillin-clavulanate (HR, 6.48; 95% CI, 1.43–29.4; P = .02) and the presence of a urinary catheter (HR, 3.81; 95% CI, 1.06–13.8; P = .04) during LTCF stay increased the risk of new FQ-resistant E. coli colonization. Conclusions. Acquisition of FQ-resistant E. coli was common, with nearly half of LTCF residents developing new FQ-resistant E. coli colonization. Further studies are needed on interventions to limit the emergence of FQ-resistant E. coli in LTCFs. PMID:23986544

A cross sectional study of animal and human colonization with Methicillin-Resistant Staphylococcus aureus (MRSA) in an Aboriginal community.

PubMed

Daley, Peter; Bajgai, Janak; Penney, Carla; Williams, Karen; Whitney, Hugh; Golding, George R; Weese, Scott

2016-07-19

Methicillin-resistant Staphylococcus aureus (MRSA) infections are common among humans in Aboriginal communities in Canada, for unknown reasons. Cross sectional study of humans and dogs in an Aboriginal community of approximately 1200 persons. Our objectives were to measure community-based prevalence of nasal MRSA colonization among humans, use multivariable logistic regression to analyze risk factors for MRSA colonization, and perform molecular typing of Staphylococci isolated to investigate interspecies transmission. 461 humans were approached for consent and 442 provided complete data. 109/442 (24.7 %, 95 % C.I. = 20.7-28.7 %) of humans were colonized with MRSA. 169/442 (38.2 %) of humans had received antibiotics in the last 12 months. Only number of rooms in the house (OR 0.86, p = 0.023) and recreational dog use (OR 7.7, p = 0.002) were significant risk factors for MRSA colonization. 95/109 (87.1 %) of MRSA strains from humans were of the same spa type (CMRSA10/USA300). 8/157 (5.1 %, 95 % C.I. = 1.7-8.5 %) of dogs were colonized with methicillin-susceptible S. aureus, and no dogs were colonized with MRSA. Human MRSA colonization in this community is very common, and a single clone is predominant, suggesting local transmission. Antibiotic use is also very common. Crowding may partially explain high colonization, but most considered risk factors including animal exposure were not predictive. Very few dogs carried human Staphylococcal strains.

Epidemiology of vancomycin-resistant enterococci in children with acute lymphoblastic leukemia at two referral centers in Tehran, Iran: a descriptive study.

PubMed

Nateghian, A; Robinson, J L; Arjmandi, K; Vosough, P; Karimi, A; Behzad, A; Navidnia, M

2011-05-01

Risk factors for colonization with vancomycin-resistant enterococci (VRE) vary by population and locale. The objective of this study was to determine the prevalence of and risk factors for VRE colonization in children with acute lymphoblastic leukemia (ALL) in Tehran. Stools were collected from children with ALL at the Ali Asghar Children's Hospital and the Mahak Pediatric Oncology Center between March 2007 and October 2008. Demographic features and potential risk factors for VRE colonization, including duration of ALL, presence of severe neutropenia in the preceding month, receipt of antibiotics in the preceding 3 months, concurrent medical problems, days of hospitalization, and the need for intensive care since the time of diagnosis of ALL, were recorded. VRE was identified from stools in 33 of 130 children with ALL (25%). No clear risk factors were identified for VRE colonization in the current study, but there was a trend towards an increased prevalence in children admitted to the intensive care unit since their ALL diagnosis (p=0.07). The VanA genotype was found in 28 of the 33 stools (85%), with all other enterococci being VanB. The prevalence of VRE colonization in children with ALL in Tehran is high. Modifiable risk factors have not been identified. The implementation of routine surveillance for colonization and an increased emphasis on adherence to standard infection control precautions may prevent spread. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Mortality risk factor analysis in colonic perforation: would retroperitoneal contamination increase mortality in colonic perforation?

PubMed

Yoo, Ri Na; Kye, Bong-Hyeon; Kim, Gun; Kim, Hyung Jin; Cho, Hyeon-Min

2017-10-01

Colonic perforation is a lethal condition presenting high morbidity and mortality in spite of urgent surgical treatment. This study investigated the surgical outcome of patients with colonic perforation associated with retroperitoneal contamination. Retrospective analysis was performed for 30 patients diagnosed with colonic perforation caused by either inflammation or ischemia who underwent urgent surgical treatment in our facility from January 2005 to December 2014. Patient characteristics were analyzed to find risk factors correlated with increased postoperative mortality. Using the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) audit system, the mortality and morbidity rates were estimated to verify the surgical outcomes. Patients with retroperitoneal contamination, defined by the presence of retroperitoneal air in the preoperative abdominopelvic CT, were compared to those without retroperitoneal contamination. Eight out of 30 patients (26.7%) with colonic perforation had died after urgent surgical treatment. Factors associated with mortality included age, American Society of Anesthesiologists (ASA) physical status classification, and the ischemic cause of colonic perforation. Three out of 6 patients (50%) who presented retroperitoneal contamination were deceased. Although the patients with retroperitoneal contamination did not show significant increase in the mortality rate, they showed significantly higher ASA physical status classification than those without retroperitoneal contamination. The mortality rate predicted from Portsmouth POSSUM was higher in the patients with retroperitoneal contamination. Patients presenting colonic perforation along with retroperitoneal contamination demonstrated severe comorbidity. However, retroperitoneal contamination was not found to be correlated with the mortality rate.

Citrinin as an accessory establishment factor of P. expansum for the colonization of apples.

PubMed

Touhami, Najim; Soukup, Sebastian T; Schmidt-Heydt, Markus; Kulling, Sabine E; Geisen, Rolf

2018-02-02

Penicillium expansum is the causal agent of blue mold decay of apples. This fungal species can produce the two important mycotoxins patulin and citrinin. It was previously shown that patulin represents a colonization factor for the infection of apples. No definitive information about the importance of citrinin for the colonization of apples is currently available. The pksCT gene of the citrinin cluster codes for the citrinin polyketide synthase. Mutants of P. expansum in which the pksCT was inactivated showed a drastic decrease in the citrinin production. In addition, the pksCT mutants were also reduced in the ability to colonize apples. Externally added citrinin restored the capacity of the mutants to colonize apples roughly to that of the wild type. A kinetic analysis of the expression of the two respective pks genes of patulin (patK) and citrinin (pksCT) revealed that both genes are highly expressed in the first phase during the colonization process. The production of patulin in the apple matrix coincides with the expression of the patK gene. Almost no citrinin could be identified analytically during the first phase but only at a later stage of the colonization. It could be demonstrated that citrinin is degraded in apples and can tightly be bound to pectin. Overall the results suggest that citrinin may have an accessory function for the establishment of the colonization guided by other factors. Copyright © 2017 Elsevier B.V. All rights reserved.

Obesity-related colon cancer: dietary factors and their mechanisms of anticancer action.

PubMed

Zeng, Huawei; Lazarova, Darina L

2012-02-01

Overweight/obesity is an epidemic in the US as well as in other developed countries, affecting two-thirds of Americans and an estimated 2.3 billion people worldwide. Obesity increases the risk for Type 2 diabetes, cardiovascular disease and cancer. For example, epidemiological studies have established a strong association between obesity and colon cancer. It is generally accepted that metabolic changes associated with overweight/obesity, particularly abdominal obesity and changes in adipocyte function, contribute to the increased risk of colon cancer. Understanding the mechanisms underlying this association is important for the development of preventive strategies for colon cancer. Part of these preventive strategies may be based on dietary factors, such as vitamins, minerals (e.g. selenium), fibre, phytochemicals and phenolic compounds. These anticancer nutrients may counteract the molecular changes associated with obesity. The present article reviews the evidence that inflammation and insulin resistance induced by obesity are the molecular mediators of the association between obesity and colon cancer. We also evaluate the evidence for the ability of dietary factors to target the obesity-induced changes and, thus, protect against colon cancer. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

High Cost of Hospitalization for Colonic Diverticular Bleeding Depended on Repeated Bleeding and Blood Transfusion: Analysis with Diagnosis Procedure Combination Data in Japan.

PubMed

Ito, Yoichiro; Sakata, Yasuhisa; Yoshida, Hisako; Nonaka, Sayuri; Fujii, Susumu; Tanaka, Yuichiro; Shirai, Shimpei; Takeshita, Eri; Akutagawa, Takashi; Kawakubo, Hiroharu; Yamamoto, Koji; Tsuruoka, Nanae; Shimoda, Ryo; Iwakiri, Ryuichi; Fujimoto, Kazuma

2017-01-01

Bleeding from a colonic diverticulum is serious in aged patients. The aim of this study was to determine the risk factors for high-cost hospitalization of colonic diverticular bleeding using the diagnosis procedure combination (DPC) data. From January 2009 to December 2015, 78 patients with colonic diverticular bleeding were identified by DPC data in Saga Medical School Hospital. All patients underwent colonic endoscopy within 3 days. The patients were divided into 2 groups: the low-cost group (DPC cost of <500,000 yen) and the high-cost group (DPC cost of >500,000 yen). Univariate analysis revealed that aging, hypertension, rebleeding, a low hemoglobin concentration at admission, and blood transfusion were risk factors for high hospitalization cost. Multivariate analysis revealed that rebleeding (OR 5.3; 95% CI 1.3-21.3; p = 0.017) and blood transfusion (OR 3.8; 95% CI 1.01-14.2; p = 0.048) were definite risk factors for high hospitalization cost. Rebleeding and blood transfusion were related to high hospitalization cost for colonic diverticular bleeding. © 2017 S. Karger AG, Basel.

Prevalence and factors associated with wound colonization by Staphylococcus spp. and Staphylococcus aureus in hospitalized patients in inland northeastern Brazil: a cross-sectional study.

PubMed

Almeida, Gilmara Celli Maia; dos Santos, Marquiony Marques; Lima, Nara Grazieli Martins; Cidral, Thiago André; Melo, Maria Celeste Nunes; Lima, Kenio Costa

2014-06-13

Infections by Staphylococcus spp. are often associated with wounds, especially in hospitalized patients. Wounds may be the source of bacteria causing cross-contamination, and are a risk factor for methicillin-resistant Staphylococcus aureus (MRSA) infection. The aim of this study was to investigate the prevalence of wound colonization by Staphylococcus spp., especially S. aureus and MRSA, in hospitalized patients, and to identify the factors associated with such colonization. This cross-sectional study enrolled patients with wounds who were hospitalized in a remote and underdeveloped inland region of northeastern Brazil with extreme poverty. Samples were collected using sterile swabs with 0.85% saline solution, and coagulase-negative Staphylococcus spp., S. aureus, and MRSA were identified using standard laboratory procedures. Data regarding the sociodemographic characteristics, antibiotic use, and comorbidities of the patients were collected using the medical records and a questionnaire. A total of 125 wounds were analyzed. The patients had a mean age of 63.88 years and a mean 3.84 years of school education. Eighty-one wounds (64.80%) were colonized by Staphylococcus spp. Twenty-five wounds (20%) were colonized by S. aureus, 32% of which were colonized by MRSA. Wound colonization by Staphylococcus spp. was associated with pneumonia or other respiratory disease (p = 0.03). Wound colonization by S. aureus was associated with nasal colonization by S. aureus (p < 0.001), fewer days of prior antibiotic use (p = 0.04), admission to a medical ward (p = 0.02), and age >65 years (p = 0.05). Among patients with wound colonization by MRSA, 37.50% had a history of prior antibiotic use, 75% had two or more comorbidities, 25% had cancer or diabetes, 50% had cardiovascular disease, and 50% died. Wounds can be the source of Staphylococcus spp. infection, and high proportions of wounds are colonized by S. aureus and MRSA. Nasal colonization by S. aureus may be a source for wound colonization by S. aureus, illustrating the importance of preventing cross-contamination in hospital environments, especially among elderly patients. Wounds should be carefully managed to prevent microbial spread, thereby assisting patient recovery and reducing healthcare costs.

The influence of the risk factor on the abdominal complications in colon injury management.

PubMed

Torba, M; Gjata, A; Buci, S; Bushi, G; Zenelaj, A; Kajo, I; Koceku, S; Kagjini, K; Subashi, K

2015-01-01

The management of colon injuries has distinctly evolved over the last three decades. However, trauma surgeons often find themselves in a dilemma, whether to perform a diversion or to perform a primary repair. The purpose of this study is to evaluate risk factors in colon injury management and their influence on abdominal complications. This is a prospective study conducted at a national level I trauma center in Tirana, Albania from January 2009 to December 2012. The data with respect to demographics, physiological risk factors, intraoperative findings, and surgical procedures were collected. Colonic injury-related morbidity and mortality were analyzed. Multivariate logistic regression analysis was performed by assessing the influence of risk factors on abdominal complications. Of the 157 patients treated with colon injury, was performed a primary repair in 107 (68.15%) of the patients and a diversion in the remaining 50 (31.85%). The mean PATI was 18.6, while 37 (23.6%) of patients had PATI greater than 25. The complications and their frequencies according to the surgical technique used (primay repair vs diversion respectively) includes: wound infections (9.3% vs 50%), anastomotic leak (1.8% vs 8.7%), and intra-abdominal abscess (1.8% vs 6.5%). The multivariate analysis identified two independent risk factors for abdominal complications: transfusions of 4 units of blood within the first 24 hours (OR = 1.2 95% CI (1.03 - 1.57) p =0.02), and diversion (OR = 9.6, 95% CI 4.4 - 21.3, p<0.001). Blood transfusions of more than 4 units within the first 24 hours and diversion during the management of destructive colon injuries are both independent risk factors for abdominal complications. The socioeconomic impact and the need for a subsequent operation in colostomy patients are strong reasons to consider primary repair in the management of colon injuries.

The influence of the risk factor on the abdominal complications in colon injury management

PubMed Central

TORBA, M.; GJATA, A.; BUCI, S.; BUSHI, G.; ZENELAJ, A.; KAJO, I.; KOCEKU, S.; KAGJINI, K.; SUBASHI, K.

2015-01-01

Introduction The management of colon injuries has distinctly evolved over the last three decades. However, trauma surgeons often find themselves in a dilemma, whether to perform a diversion or to perform a primary repair. The purpose of this study is to evaluate risk factors in colon injury management and their influence on abdominal complications. Patients and methods This is a prospective study conducted at a national level I trauma center in Tirana, Albania from January 2009 to December 2012. The data with respect to demographics, physiological risk factors, intraoperative findings, and surgical procedures were collected. Colonic injury-related morbidity and mortality were analyzed. Multivariate logistic regression analysis was performed by assessing the influence of risk factors on abdominal complications. Results Of the 157 patients treated with colon injury, was performed a primary repair in 107 (68.15%) of the patients and a diversion in the remaining 50 (31.85%). The mean PATI was 18.6, while 37 (23.6%) of patients had PATI greater than 25. The complications and their frequencies according to the surgical technique used (primay repair vs diversion respectively) includes: wound infections (9.3% vs 50%), anastomotic leak (1.8% vs 8.7%), and intra-abdominal abscess (1.8% vs 6.5%). The multivariate analysis identified two independent risk factors for abdominal complications: transfusions of 4 units of blood within the first 24 hours (OR = 1.2 95% CI (1.03 –1.57) p =0.02), and diversion (OR = 9.6, 95% CI 4.4 – 21.3, p<0.001). Conclusion Blood transfusions of more than 4 units within the first 24 hours and diversion during the management of destructive colon injuries are both independent risk factors for abdominal complications. The socioeconomic impact and the need for a subsequent operation in colostomy patients are strong reasons to consider primary repair in the management of colon injuries. PMID:26017103

Using Bayesian modelling to investigate factors governing antibiotic-induced Candida albicans colonization of the GI tract

PubMed Central

Shankar, Jyoti; Solis, Norma V.; Mounaud, Stephanie; Szpakowski, Sebastian; Liu, Hong; Losada, Liliana; Nierman, William C.; Filler, Scott G.

2015-01-01

Receipt of broad-spectrum antibiotics enhances Candida albicans colonization of the GI tract, a risk factor for haematogenously-disseminated candidiasis. To understand how antibiotics influence C. albicans colonization, we treated mice orally with vancomycin or a combination of penicillin, streptomycin, and gentamicin (PSG) and then inoculated them with C. albicans by gavage. Only PSG treatment resulted in sustained, high-level GI colonization with C. albicans. Furthermore, PSG reduced bacterial diversity in the colon much more than vancomycin. Both antibiotic regimens significantly reduced IL-17A, IL-21, IL-22 and IFN-γ mRNA levels in the terminal ileum but had limited effect on the GI fungal microbiome. Through a series of models that employed Bayesian model averaging, we investigated the associations between antibiotic treatment, GI microbiota, and host immune response and their collective impact on C. albicans colonization. Our analysis revealed that bacterial genera were typically associated with either C. albicans colonization or altered cytokine expression but not with both. The only exception was Veillonella, which was associated with both increased C. albicans colonization and reduced IL-21 expression. Overall, antibiotic-induced changes in the bacterial microbiome were much more consistent determinants of C. albicans colonization than either the GI fungal microbiota or the GI immune response. PMID:25644850

An unusual colon atresia in a calf: at the junction of the distal loop and transverse colon. A brief overview

PubMed Central

Lombardero, Matilde; Yllera, María del Mar

2014-01-01

Congenital defects are those abnormalities present at birth. During embryogenesis, many anomalies can occur. The primitive gut tube lengthens quickly and rotates, allowing the gastrointestinal tract acquire its final position and orientation. Because the colon of large animals is complex, most changes occur in this segment. Thus, in ruminants, colon atresia is the most frequent malformation, affecting mainly ascending colon, at the level of the spiral loop. There are no previous references about a very atypical colon atresia at the junction of distal loop and transverse colon, such we have described in a 5-day-old calf, after a history of abdominal distention and absence of feces at birth, even with a patent anal opening. Atresia coli was detected at distal position of the typical colon atresia, at the junction of distal loop and transverse colon. In addition, the distal blind end was bent into a U-shape supported by the mesocolon. Besides the anatomical findings of this worthwhile atresia coli we discuss its possible etiology, in which local factors, such as a compromised blood supply during embryogenesis, are more consistent than genetic factors. Finding out the causes of atresia coli would help to reduce its incidence, lessen animal suffering and economic loss. PMID:25495264

Marriage is a dependent risk factor for mortality of colon adenocarcinoma without a time-varying effect

PubMed Central

Yu, Wei; Chen, Jie; Xiong, Weibin; Chen, Shuang; Yu, Li

2017-01-01

Background It has been well recognized that the effects of many prognostic factors could change during long-term follow-up. Although marriage has been proven to be a significant prognostic factor for the survival of colon cancer, whether the effect of marriage is constant with time remain unknown. This study analyzed the impact of marital status on the mortality of colon cancer patients with an extended Cox model that allowed for time-varying effects. Methods We identified 71,955 patients who underwent colectomy between 2004 and 2009 to treat colon adenocarcinoma from the Surveilance, Epidemiology and End Results Database. The multivariate extended Cox model was used to evaluate the effect of marital status on all-cause mortality, while the Fine-Gray competing risks model was used for colon cancer-specific mortality, with death from other causes as the competing risk. Results The unmarried patients carried a 1.37-fold increased risk of all-cause mortality compared with the married patients (95%CI: 1.33-1.40; p<0.001), and the hazard ratio remained constant over time. Being unmarried was at a higher risk of death from colon adenocarcinoma as well as death from other causes. Four variables including tumor site, tumor grade, sex and TNM stage were proved to have time-varying effects on survival. Conclusions Marriage is a dependent prognosis factor for survival of surgically treated colon adenocarcinoma patients. Psychological interventions are suggested to improve receipt of treatment among unmarried patients, as their poor survival may be due to the inefficient treatment. PMID:28423614

Marriage is a dependent risk factor for mortality of colon adenocarcinoma without a time-varying effect.

PubMed

Liu, Minling; Li, Lixian; Yu, Wei; Chen, Jie; Xiong, Weibin; Chen, Shuang; Yu, Li

2017-03-21

It has been well recognized that the effects of many prognostic factors could change during long-term follow-up. Although marriage has been proven to be a significant prognostic factor for the survival of colon cancer, whether the effect of marriage is constant with time remain unknown. This study analyzed the impact of marital status on the mortality of colon cancer patients with an extended Cox model that allowed for time-varying effects. We identified 71,955 patients who underwent colectomy between 2004 and 2009 to treat colon adenocarcinoma from the Surveilance, Epidemiology and End Results Database. The multivariate extended Cox model was used to evaluate the effect of marital status on all-cause mortality, while the Fine-Gray competing risks model was used for colon cancer-specific mortality, with death from other causes as the competing risk. The unmarried patients carried a 1.37-fold increased risk of all-cause mortality compared with the married patients (95%CI: 1.33-1.40; p<0.001), and the hazard ratio remained constant over time. Being unmarried was at a higher risk of death from colon adenocarcinoma as well as death from other causes. Four variables including tumor site, tumor grade, sex and TNM stage were proved to have time-varying effects on survival. Marriage is a dependent prognosis factor for survival of surgically treated colon adenocarcinoma patients. Psychological interventions are suggested to improve receipt of treatment among unmarried patients, as their poor survival may be due to the inefficient treatment.

Complications of acromegaly: thyroid and colon.

PubMed

Tirosh, Amit; Shimon, Ilan

2017-02-01

In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon. We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly. This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly. Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.

Oxalobacter formigenes–Derived Bioactive Factors Stimulate Oxalate Transport by Intestinal Epithelial Cells

PubMed Central

Arvans, Donna; Jung, Yong-Chul; Antonopoulos, Dionysios; Koval, Jason; Granja, Ignacio; Bashir, Mohamed; Karrar, Eltayeb; Roy-Chowdhury, Jayanta; Musch, Mark; Asplin, John; Chang, Eugene

2017-01-01

Hyperoxaluria is a major risk factor for kidney stones and has no specific therapy, although Oxalobacter formigenes colonization is associated with reduced stone risk. O. formigenes interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion, via an unknown secretagogue. The difficulties in sustaining O. formigenes colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of O. formigenes culture conditioned medium (CM) on apical 14C-oxalate uptake by human intestinal Caco-2-BBE cells. Compared with control medium, O. formigenes CM significantly stimulated oxalate uptake (>2.4-fold), whereas CM from Lactobacillus acidophilus did not. Treating the O. formigenes CM with heat or pepsin completely abolished this bioactivity, and selective ultrafiltration of the CM revealed that the O. formigenes–derived factors have molecular masses of 10–30 kDa. Treatment with the protein kinase A inhibitor H89 or the anion exchange inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid completely blocked the CM-induced oxalate transport. Knockdown of the oxalate transporter SLC26A6 also significantly restricted the induction of oxalate transport by CM. In a mouse model of primary hyperoxaluria type 1, rectal administration of O. formigenes CM significantly reduced (>32.5%) urinary oxalate excretion and stimulated (>42%) distal colonic oxalate secretion. We conclude that O. formigenes–derived bioactive factors stimulate oxalate transport in intestinal cells through mechanisms including PKA activation. The reduction in urinary oxalate excretion in hyperoxaluric mice treated with O. formigenes CM reflects the in vivo retention of biologic activity and the therapeutic potential of these factors. PMID:27738124

Colonization with third-generation cephalosporin-resistant Enterobacteriaceae on hospital admission: prevalence and risk factors.

PubMed

Hamprecht, A; Rohde, A M; Behnke, M; Feihl, S; Gastmeier, P; Gebhardt, F; Kern, W V; Knobloch, J K; Mischnik, A; Obermann, B; Querbach, C; Peter, S; Schneider, C; Schröder, W; Schwab, F; Tacconelli, E; Wiese-Posselt, M; Wille, T; Willmann, M; Seifert, H; Zweigner, J

2016-10-01

The objectives of this study were to prospectively assess the rectal carriage rate of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) in non-ICU patients on hospital admission and to investigate resistance mechanisms and risk factors for carriage. Adult patients were screened for 3GCREB carriage at six German tertiary care hospitals in 2014 using rectal swabs or stool samples. 3GCREB isolates were characterized by phenotypic and molecular methods. Each patient answered a questionnaire about potential risk factors for colonization with MDR organisms (MDROs). Univariable and multivariable risk factor analyses were performed to identify factors associated with 3GCREB carriage. Of 4376 patients, 416 (9.5%) were 3GCREB carriers. Escherichia coli was the predominant species (79.1%). ESBLs of the CTX-M-1 group (67.3%) and the CTX-M-9 group (16.8%) were the most frequent β-lactamases. Five patients (0.11%) were colonized with carbapenemase-producing Enterobacteriaceae. The following risk factors were significantly associated with 3GCREB colonization in the multivariable analysis (P < 0.05): centre; previous MDRO colonization (OR = 2.12); antibiotic use within the previous 6 months (OR = 2.09); travel outside Europe (OR = 2.24); stay in a long-term care facility (OR = 1.33); and treatment of gastroesophageal reflux disease (GERD) (OR = 1.22). To our knowledge, this is the largest admission prevalence study of 3GCREB in Europe. The observed prevalence of 9.5% 3GCREB carriage was higher than previously reported and differed significantly among centres. In addition to previously identified risk factors, the treatment of GERD proved to be an independent risk factor for 3GCREB colonization. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Biotic interactions affect the colonization behavior of aquatic detritivorous macroinvertebrates in a heterogeneous environment

NASA Astrophysics Data System (ADS)

Verschut, Thomas A.; Meineri, Eric; Basset, Alberto

2015-05-01

It has previously been suggested that macroinvertebrates actively search for suitable patches to colonize. However, it is not well understood how the spatial arrangement of patches can affect colonization rates. In this study, we determined the importance of the environmental factors (distance, connectivity and resource availability) for patch colonization in an experimental system using Gammarus aequicauda (Amphipoda), Lekanesphaera hookeri (Isopoda) and Ecrobia ventrosa (Gastropoda). Furthermore, we also assessed how the relative importance of each of these environmental factors differed in interactions between the three species. The single species experiments showed that distance was the most important factor for G. aequicauda and E. ventrosa. However, while E. ventrosa preferred patches close to the release point, G. aequicauda strongly preferred patches further from the release point. High resource availability was a strong determinant for the patch colonization of G. aequicauda and L. hookeri. Connectivity was only of moderate importance in the study system for L. hookeri and E. ventrosa. The effects of the environmental factors were strongly affected by interspecific interactions in the multispecies experiments. For G. aequicauda, the distance preference was lowered in the presence of E. ventrosa. Moreover, while for L. hookeri the effect of resource availability was ruled out by the species interactions, resource availability gained importance for E. ventrosa in the presence of any of the other species. Our results suggest a strong link between environmental factors and biotic interactions in the colonization of habitat patches and indicate that the effect of biotic interactions is especially important for species sharing similar traits.

Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease.

PubMed

Mattii, Letizia; Ippolito, Chiara; Segnani, Cristina; Battolla, Barbara; Colucci, Rocchina; Dolfi, Amelio; Bassotti, Gabrio; Blandizzi, Corrado; Bernardini, Nunzia

2013-01-01

The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.

Transverse colon volvulus in neurologicaly imparied patient as an emergency surgical condition: A case report.

PubMed

Miličković, Maja; Savić, Đorđe; Stanković, Nikola; Vukadin, Miroslav; Božić, Dejana

2017-01-01

Transverse colon volvulus is an uncommon cause of bowel obstruction in general. Predisposing factors are mental retardation, dysmotility disorders, chronic constipation and congenital megacolon. We presented transverse colon volvulus in a 16-year-old boy with cerebral palsy. Chronic constipation in neurologicaly impaired patient was a risk factor predisposing to volvulus. The patient was admitted to the hospital with enormous abdominal distension and acute respiratory insufficiency. A boy was emergently taken to the operating room for exploratory laparotomy. During the surgery, a 360º clockwise volvulus of the transverse colon was found. After reduction of volvulus, an enormous transverse colon was resected and colostomy was formed. In the postoperative period, despite the good functioning of stoma and intraabdominal normotension, numerous and long lasting respiratory problems developed. The patient was discharged from our institution after 8 months. Though very rare in pediatric group, the possibility of a transverse colon volvulus must be considered in the differential diagnosis of acute large bowel obstruction.

Triclosan Promotes Staphylococcus aureus Nasal Colonization

PubMed Central

Syed, Adnan K.; Ghosh, Sudeshna; Love, Nancy G.; Boles, Blaise R.

2014-01-01

ABSTRACT The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. PMID:24713325

Colonization with extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species in long-term care facility residents.

PubMed

Lautenbach, Ebbing; Han, Jennifer; Santana, Evelyn; Tolomeo, Pam; Bilker, Warren B; Maslow, Joel

2012-03-01

We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EB) in the long-term care facility (LTCF) setting. Colonization prevalence differed significantly across the 3 LTCFs evaluated in the study, with recent use of levofloxacin and fecal incontinence demonstrating borderline significant associations with ESBL-EB colonization.

Colonization with Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella Species in Long-Term Care Facility Residents

PubMed Central

Lautenbach, Ebbing; Han, Jennifer; Santana, Evelyn; Tolomeo, Pam; Bilker, Warren B.; Maslow, Joel

2012-01-01

We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EB) in the long-term care facility (LTCF) setting. Colonization prevalence differed significantly across the 3 LTCFs evaluated in the study, with recent use of levofloxacin and fecal incontinence demonstrating borderline significant associations with ESBL-EB colonization. PMID:22314070

Surveillance of Diarrheagenic Escherichia coli Strains Isolated from Diarrhea Cases from Children, Adults and Elderly at Northwest of Mexico

PubMed Central

Canizalez-Roman, Adrian; Flores-Villaseñor, Héctor M.; Gonzalez-Nuñez, Edgar; Velazquez-Roman, Jorge; Vidal, Jorge E.; Muro-Amador, Secundino; Alapizco-Castro, Gerardo; Díaz-Quiñonez, J. Alberto; León-Sicairos, Nidia

2016-01-01

Diarrheagenic Escherichia coli (DEC) strains are a main cause of gastrointestinal disease in developing countries. In this study we report the epidemiologic surveillance in a 4-year period (January 2011 to December 2014) of DEC strains causing acute diarrhea throughout the Sinaloa State, Mexico. DEC strains were isolated from outpatients of all ages with acute diarrhea (N = 1,037). Specific DEC pathotypes were identified by PCR-amplification of genes encoding virulence factors. The adhesion phenotype and antibiotic resistance were also investigated. DEC strains were detected in 23.3% (242/1037) of cases. The most frequently DEC strain isolated was EAEC [(12.2%), 126/242] followed by EPEC [(5.1%), 53/242], ETEC [(4.3%), 43/242] DAEC [(1.4%), 15/242], STEC [(0.3%), 3/242], and EIEC [(0.2%), 2/242]. EHEC strains were not detected. Overall DEC strains were more prevalent in children ≤2 years of age with EPEC strains the most common of DEC pathotypes. While ∼65% of EAEC strains were classified as typical variant based on the aggregative adherence to in vitro cultures of HEp-2 cells, a high proportion of EPEC strains was classified as atypical strains. EAEC, EPEC, ETEC, and DAEC strains were distributed in the north, central and south regions of Sinaloa state. Among all DEC strains, >90% were resistant to at least one commonly prescribed antibiotic. Strains were commonly resistant to first-line antibiotics such as tetracycline, ampicillin, and sulfamethoxazole-trimethoprim. Furthermore, more than 80% of DEC isolates were multi-drug resistant and EPEC and DAEC were the categories with major proportion of this feature. In conclusion, in nearly one out of four cases of acute diarrhea in Northwestern Mexico a multi-drug resistant DEC strain was isolated, in these cases EAEC was the most prevalent (52%) pathotype. PMID:27965648

Mode of Birth Influences Preterm Infant Intestinal Colonization with Bacteroides Over the Early Neonatal Period

PubMed Central

Gregory, Katherine E.; LaPlante, Rose D.; Shan, Gururaj; Kumar, Deepak Vijaya; Gregas, Matt

2015-01-01

Background Intestinal colonization during infancy is important to short and long term health outcomes. Bacteroides, an early member of the intestinal microbiome, are necessary for breaking down complex molecules within the intestine and function to assist the body’s immune system in fighting against potentially harmful pathogens. Little is known about the colonization pattern of Bacteroides in preterm infants during the early neonatal period. Purpose This study measured Bacteroides colonization during the early neonatal period in a population of preterm infants based on clinical factors including mode of birth, antibiotics, and nutrition. Methods Bacterial DNA was isolated from 144 fecal samples from 29 preterm infants and analyzed using quantitative real time polymerase chain reaction (PCR). Analyses included liner mixed models to determine which clinical factors affect Bacteroides colonization of the infant gut. Results We found that infants born via vaginal canal had a higher rate of increase in Bacteroides than infants born via Cesarean section (p<.001). We did not find significant associations between antibiotic administration and differences in nutritional exposures with Bacteroides colonization. Implications for Practice These findings highlight the significant influence of mode of birth on Bacteroides colonization. While mode of birth is not always modifiable, these study findings may help develop interventions for preterm infants born via Cesarean section aimed at overcoming delayed Bacteroides colonization. Implications for Research Greater study of the intestinal microbiome and the clinical factors relevant to the preterm infant is needed so that interventions may be developed and tested, resulting in optimal microbial and immune health. PMID:26551793

Risk Factors for Pneumococcal Colonization of the Nasopharynx in Alaska Native Adults and Children.

PubMed

Reisman, Jonathan; Rudolph, Karen; Bruden, Dana; Hurlburt, Debby; Bruce, Michael G; Hennessy, Thomas

2014-06-01

Alaska Native children have high invasive pneumococcal disease (IPD) rates, and lack of in-home running water has been shown to have a significant association with infection. Pneumococcal conjugate vaccines reduced IPD; however, this population saw substantial replacement disease and colonization with nonvaccine serotypes. We evaluated risk factors for nasopharyngeal pneumococcal colonization in Alaska Native adults and children. We conducted annual surveys from 2008 through 2011 of residents of all ages in 8 rural Alaskan villages. Interviews were conducted, medical charts were reviewed, and nasopharyngeal swabs were cultured for Streptococcus pneumoniae. Multivariate logistic regression models were developed for 3 age groups (under 10 years, 10-17 years, and 18 years and older) to determine risk factors for colonization. We obtained 12 535 nasopharyngeal swabs from 4980 participants. Our population lived in severely crowded conditions, and 48% of households lacked in-home running water. In children <10 years, colonization was associated with lack of in-home running water, household crowding, and more children in the home. Pneumococcal vaccination status was not associated with colonization. In older children and adults, increased number of persons in the household was associated with pneumococcal colonization. Higher colonization prevalence may partially explain increased IPD rates seen in those lacking in-home water services. Improving availability of sanitation services and reducing household crowding may reduce the burden of IPD in this population. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Study of a Library and Information Science Adademic Program Accredited by State (TEA), Regional (SACS), and National (NCATE) Accrediting Associations.

ERIC Educational Resources Information Center

Correll, Lou P.

Following the substitution of a Learning Resources Specialist's (LRS) certification for the traditional school librarian's certification in Texas and the subsequent merging of the Departments of Library and Information Science (LIS) and Educational Media and Technology (ETEC) at East Texas State University (ETSU), the immediate supervisors of 28…

Ingestion of transgenic carrots expressing the Escherichia coli heat-labile enterotoxin B subunit protects mice against cholera toxin challenge.

PubMed

Rosales-Mendoza, Sergio; Soria-Guerra, Ruth Elena; López-Revilla, Rubén; Moreno-Fierros, Leticia; Alpuche-Solís, Angel Gabriel

2008-01-01

Diarrheal diseases caused by Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are worldwide health problems that might be prevented with vaccines based on edible plants expressing the B subunit from either the cholera toxin (CTB) or the E. coli heat labile toxin (LTB). In this work we analyzed the immunity induced in Balb/c mice by ingestion of three weekly doses of 10 mug of LTB derived from transgenic carrot material. Although the anti-LTB serum immunoglobulin G (IgG) and intestinal IgA antibody responses were higher with 10 mug-doses of pure bacterial recombinant LTB (rLTB), the transgenic carrot material also elicited significant serum and intestinal antibody responses. Serum anti-LTB IgG1 antibodies predominated over IgG2a antibodies, suggesting that mainly Th2 responses were induced. A decrease of intestinal fluid accumulation after cholera toxin challenge was observed in mice immunized with either rLTB or LTB-containing carrot material. These results demonstrate that ingestion of carrot-derived LTB induces antitoxin systemic and intestinal immunity in mice and suggest that transgenic carrots expressing LTB may be used as an effective edible vaccine against cholera and ETEC diarrhea in humans.

A structural mechanism for bacterial autotransporter glycosylation by a dodecameric heptosyltransferase family

PubMed Central

Yao, Qing; Lu, Qiuhe; Wan, Xiaobo; Song, Feng; Xu, Yue; Hu, Mo; Zamyatina, Alla; Liu, Xiaoyun; Huang, Niu; Zhu, Ping; Shao, Feng

2014-01-01

A large group of bacterial virulence autotransporters including AIDA-I from diffusely adhering E. coli (DAEC) and TibA from enterotoxigenic E. coli (ETEC) require hyperglycosylation for functioning. Here we demonstrate that TibC from ETEC harbors a heptosyltransferase activity on TibA and AIDA-I, defining a large family of bacterial autotransporter heptosyltransferases (BAHTs). The crystal structure of TibC reveals a characteristic ring-shape dodecamer. The protomer features an N-terminal β-barrel, a catalytic domain, a β-hairpin thumb, and a unique iron-finger motif. The iron-finger motif contributes to back-to-back dimerization; six dimers form the ring through β-hairpin thumb-mediated hand-in-hand contact. The structure of ADP-D-glycero-β-D-manno-heptose (ADP-D,D-heptose)-bound TibC reveals a sugar transfer mechanism and also the ligand stereoselectivity determinant. Electron-cryomicroscopy analyses uncover a TibC–TibA dodecamer/hexamer assembly with two enzyme molecules binding to one TibA substrate. The complex structure also highlights a high efficient hyperglycosylation of six autotransporter substrates simultaneously by the dodecamer enzyme complex. DOI: http://dx.doi.org/10.7554/eLife.03714.001 PMID:25310236

Operative factors associated with short-term outcome in horses with large colon volvulus: 47 cases from 2006 to 2013

PubMed Central

Gonzalez, L. M.; Fogle, C. A.; Baker, W. T.; Hughes, F. E.; Law, J. M.; Motsinger-Reif, A. A.; Blikslager, A. T.

2014-01-01

Summary Reasons for performing the study There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus. Objectives To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus. Study Design Retrospective cohort study Methods Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson & Smith and Chino Valley Equine Hospitals between 2006–2013 undergoing an exploratory celiotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitial: crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital). Results Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitial: crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be significantly associated with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified haemorrhage area measurement strengthened the association of haemorrhage with non-survival in cases of large colon volvulus. Conclusions Histomorphometric measurements of interstitial: crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study. Accurate quantification of mucosal haemorrhage at the time of surgery may improve veterinary surgeons’ prognostic capabilities in horses with large colon volvulus. PMID:24735170

Operative factors associated with short-term outcome in horses with large colon volvulus: 47 cases from 2006 to 2013.

PubMed

Gonzalez, L M; Fogle, C A; Baker, W T; Hughes, F E; Law, J M; Motsinger-Reif, A A; Blikslager, A T

2015-05-01

There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus. To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus. Retrospective cohort study. Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson and Smith and Chino Valley Equine Hospitals between 2006 and 2013 that underwent an exploratory coeliotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitium-to-crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital). Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitium-to-crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be associated significantly with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified measurement of haemorrhage area strengthened the association of haemorrhage with nonsurvival in cases of large colon volvulus. Histomorphometric measurements of interstitium-to-crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study. Accurate quantification of mucosal haemorrhage at the time of surgery may improve veterinary surgeons' prognostic capabilities in horses with large colon volvulus. © 2014 EVJ Ltd.

Relationship between antenatal group B streptococcal vaginal colonization and premature labour

PubMed Central

Allen, Upton; Nimrod, Carl; MacDonald, Noni; Toye, Baldwin; Stephens, Derek; Marchessault, Victor

1999-01-01

OBJECTIVE: To determine whether a population of pregnant women with group B streptococcal (GBS) vaginal colonization had an increased risk of specific epidemiological and intrapartum risk factors for early onset GBS disease. SETTING: Tertiary university centre in Ottawa, Ontario. DESIGN: Hospital-based retrospective cohort study. METHODS: Pregnant women who gave birth during a four-month period in 1994 were included in the study. Potential GBS risk factors were obtained from a review of medical records. The prevalence of each risk factor in colonized and noncolonized women was examined using χ2 or Fisher’s exact test. Multiple logistic regression was performed. RESULTS: A total of 986 women, including 94 (9.5%) women colonized with GBS, were studied. The proportion of women younger than 20 years of age in the colonized group was 2.1% (two of 94) versus 4.6% (41 of 891) in the noncolonized group (P=0.28). Similar rates of multiple births were observed among the colonized and noncolonized groups (2.1% [two of 94] versus 2.5% [22 of 891], respectively) (P=0.94). Likewise, there were no significant differences in either group in the prevalence of a previous pregnancy affected by GBS or diabetes mellitus (P=0.82 and P=0.79, respectively). Multivariable analyses indicated that women who were colonized with GBS were more than twice as likely to deliver prematurely (below 37 weeks’ gestational age) (odds ratio [OR] 2.43, 95% CI 1.39 to 4.23). Similarly, colonized women were more likely to be febrile during labour (at least 38°C) (OR 5.05, 95% CI 1.70 to 15.02). CONCLUSION: GBS vaginal colonization was associated with premature labour and intrapartum pyrexia in the population studied. According to Canadian and American guidelines, women with GBS vaginal colonization qualify for intrapartum chemoprophylaxis. The study results suggest that the identification of women at risk of premature labour may be one advantage of early prenatal screening for GBS. PMID:20212961

Candida colonization as a risk marker for invasive candidiasis in mixed medical-surgical intensive care units: development and evaluation of a simple, standard protocol.

PubMed

Lau, Anna F; Kabir, Masrura; Chen, Sharon C-A; Playford, E Geoffrey; Marriott, Deborah J; Jones, Michael; Lipman, Jeffrey; McBryde, Emma; Gottlieb, Thomas; Cheung, Winston; Seppelt, Ian; Iredell, Jonathan; Sorrell, Tania C

2015-04-01

Colonization with Candida species is an independent risk factor for invasive candidiasis (IC), but the minimum and most practicable parameters for prediction of IC have not been optimized. We evaluated Candida colonization in a prospective cohort of 6,015 nonneutropenic, critically ill patients. Throat, perineum, and urine were sampled 72 h post-intensive care unit (ICU) admission and twice weekly until discharge or death. Specimens were cultured onto chromogenic agar, and a subset underwent molecular characterization. Sixty-three (86%) patients who developed IC were colonized prior to infection; 61 (97%) tested positive within the first two time points. The median time from colonization to IC was 7 days (range, 0 to 35). Colonization at any site was predictive of IC, with the risk of infection highest for urine colonization (relative risk [RR]=2.25) but with the sensitivity highest (98%) for throat and/or perineum colonization. Colonization of ≥2 sites and heavy colonization of ≥1 site were significant independent risk factors for IC (RR=2.25 and RR=3.7, respectively), increasing specificity to 71% to 74% but decreasing sensitivity to 48% to 58%. Molecular testing would have prompted a resistance-driven decision to switch from fluconazole treatment in only 11% of patients infected with C. glabrata, based upon species-level identification alone. Positive predictive values (PPVs) were low (2% to 4%) and negative predictive values (NPVs) high (99% to 100%) regardless of which parameters were applied. In the Australian ICU setting, culture of throat and perineum within the first two time points after ICU admission captures 84% (61/73 patients) of subsequent IC cases. These optimized parameters, in combination with clinical risk factors, should strengthen development of a setting-specific risk-predictive model for IC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Determinants and Duration of Impact of Early Gut Bacterial Colonization.

PubMed

Edwards, Christine Ann

2017-01-01

An increasing number of studies show low diversity of the gut microbiome in those with chronic diseases such as obesity, inflammatory bowel disease, and allergy. Manipulation of the microbiota may promote health. However, the adult microbiota is stable and may be difficult to change. Understanding the fixed and modifiable factors, which determine colonization in early life, may provide strategies for acquisition of a health-promoting microbiome. Not enough is known about the long-term effects of established determinants of gut colonization, including delivery mode, perinatal antibiotics, and infant diet. It has been suggested that weaning onto solid diet containing non-digestible carbohydrates and cessation of breastfeeding are key stages in the colonization process. In addition, the microbiome of the placenta, amniotic fluid, and breast milk, alongside vaginal and fecal bacteria, may aid the transfer of maternal bacteria to the infant. However, methodological issues such as contamination during collection and/or analysis should be considered. Key Messages: The factors determining early colonization are becoming more evident. However, longitudinal studies of microbiome maturation into late childhood and adulthood are required. The nutrition and health status of the mother before, during, and after birth may be major factors in the early colonization of the infant. © 2017 S. Karger AG, Basel.

Toxigenic Clostridium difficile colonization among hospitalised adults; risk factors and impact on survival.

PubMed

Behar, Laura; Chadwick, David; Dunne, Angela; Jones, Christopher I; Proctor, Claire; Rajkumar, Chakravarthi; Sharratt, Paula; Stanley, Philip; Whiley, Angela; Wilks, Mark; Llewelyn, Martin J

2017-07-01

To establish risk factors for Clostridium difficile colonization among hospitalized patients in England. Patients admitted to elderly medicine wards at three acute hospitals in England were recruited to a prospective observational study. Participants were asked to provide a stool sample as soon as possible after enrolment and then weekly during their hospital stay. Samples were cultured for C. difficile before ribotyping and toxin detection by PCR. A multivariable logistic regression model of risk factors for C. difficile colonization was fitted from univariable risk factors significant at the p < 0.05 level. 410/727 participants submitted ≥1 stool sample and 40 (9.8%) carried toxigenic C. difficile in the first sample taken. Ribotype 106 was identified three times and seven other ribotypes twice. No ribotype 027 strains were identified. Independent predictors of colonization were previous C. difficile infection (OR 4.53 (95% C.I. 1.33-15.48) and malnutrition (MUST score ≥2) (OR 3.29 (95% C.I. 1.47-7.35)). Although C. difficile colonised patients experienced higher 90-day mortality, colonization was not an independent risk for death. In a non-epidemic setting patients who have previously had CDI and have a MUST score of ≥2 are at increased risk of C. difficile colonization and could be targeted for active surveillance to prevent C. difficile transmission. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Risk factors for colonization and infection by Pseudomonas aeruginosa in patients hospitalized in intensive care units in France.

PubMed

Hoang, S; Georget, A; Asselineau, J; Venier, A-G; Leroyer, C; Rogues, A M; Thiébaut, R

2018-01-01

To assess the role of environment, medical care and individual risks factors for P. aeruginosa colonization and infection. A French multicentric prospective study involved ten ICUs for a five months period. Every adult patient newly hospitalized in ICUs with no P. aeruginosa carriage up to 48 hours after admission was included and weekly screened before discharge or death. Screening swabs were either rectal, sputum or oropharyngeal samples. Hydric environment was also sampled each week. Data on patient clinical features, environmental and device exposures, and antibiotics supports were regularly collected. Multivariate analysis was performed with a multistate model. The overall prevalence of P. aeruginosa carriage was 15.3% (201/1314). Risk factors associated with patient colonization were: use of inactive antibiotics against P. aeruginosa (HR = 1.60 [1.15-2.21] p<0.01), tap water contamination at the entry in the room (HR = 1.66 [1.01-2.27] p<0.05) and mechanical invasive ventilation (HR = 4.70 [2.66-8.31] p<0.0001). Active antibiotics prevented from colonization (HR = 0.67 [0.48-0.93] p = 0.02) and from infection (HR = 0.64 [0.41-1.01] p = 0.05). Interaction between hydric environment antibiotics support was not statistically associated with patient colonization. Hydric contamination and antibiotics pressure seem to remain key independent risk factors in P. aeruginosa colonization. These results advocate the need to carry on preventive and targeted interventions toward healthcare associated infections.

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains.

PubMed

Stoesser, Nicole; Eyre, David W; Quan, T Phuong; Godwin, Heather; Pill, Gemma; Mbuvi, Emily; Vaughan, Alison; Griffiths, David; Martin, Jessica; Fawley, Warren; Dingle, Kate E; Oakley, Sarah; Wanelik, Kazimierz; Finney, John M; Kachrimanidou, Melina; Moore, Catrin E; Gorbach, Sherwood; Riley, Thomas V; Crook, Derrick W; Peto, Tim E A; Wilcox, Mark H; Walker, A Sarah

2017-01-01

Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases. 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0-10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%). In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread.

Clostridium difficile colonization and infection in patients with hepatic cirrhosis.

PubMed

Yan, Dong; Chen, Yunbo; Lv, Tao; Huang, Yandi; Yang, Jiezuan; Li, Yongtao; Huang, Jianrong; Li, Lanjuan

2017-10-01

The aim of this study was to investigate the toxigenic Clostridium difficile colonization (CDC, colonization with toxigenic C. difficile but without symptoms) and C. difficile infection (CDI, active C. difficile infection resulting in disease symptoms) in hepatic cirrhosis patients, identify the risk factors of CDC, and determine the correlation between CDC and CDI. The strains of toxigenic C. difficile were isolated from patients with hepatic cirrhosis within 48 h after admission, followed by multilocus sequence typing (MLST). Patients were divided into toxigenic CDC group and noncolonized (NC) group according to the colonization. Logistic regression analysis was performed to analyse the risk factors for the CDC. Besides, the CDI incidence was compared between the two groups. Colonization of toxigenic C. difficile was identified in 104 cases (19.8 %). Eighteen sequence types (STs) were identified, among which ST-3, ST-54, ST-35 and ST-37 were the predominant types. Child-Pugh class C(relative risk, RR, 3.025; 95 % CI: 1.410-6.488), decrease of prothrombin time activity (PTA) (RR 2.180; 95 % CI: 1.368-3.476), decrease of platelet (RR 2.746; 95 % CI: 0.931-8.103) and concurrent hepatic encephalopathy (RR 1.740; 95 % CI: 1.012-2.990) were identified as the risk factors for the hepatic cirrhosis patients with CDC. The CDI incidence in the CDC group was also significantly higher than that of the NC group (26.0 % vs 1.7 %, P<0.001). An carriage rate of 19.8 % was reported in the hepatic cirrhosis patients with C. difficile colonization. Child's class C, decrease of PTA and platelet, and concurrent hepatic encephalopathy were the risk factors for the hepatic cirrhosis patients with C. difficile colonization. Hepatic cirrhosis patients with C. difficile colonization were more susceptible to CDI.

Prevalence and factors associated with wound colonization by Staphylococcus spp. and Staphylococcus aureus in hospitalized patients in inland northeastern Brazil: a cross-sectional study

PubMed Central

2014-01-01

Background Infections by Staphylococcus spp. are often associated with wounds, especially in hospitalized patients. Wounds may be the source of bacteria causing cross-contamination, and are a risk factor for methicillin-resistant Staphylococcus aureus (MRSA) infection. The aim of this study was to investigate the prevalence of wound colonization by Staphylococcus spp., especially S. aureus and MRSA, in hospitalized patients, and to identify the factors associated with such colonization. Methods This cross-sectional study enrolled patients with wounds who were hospitalized in a remote and underdeveloped inland region of northeastern Brazil with extreme poverty. Samples were collected using sterile swabs with 0.85% saline solution, and coagulase-negative Staphylococcus spp., S. aureus, and MRSA were identified using standard laboratory procedures. Data regarding the sociodemographic characteristics, antibiotic use, and comorbidities of the patients were collected using the medical records and a questionnaire. Results A total of 125 wounds were analyzed. The patients had a mean age of 63.88 years and a mean 3.84 years of school education. Eighty-one wounds (64.80%) were colonized by Staphylococcus spp. Twenty-five wounds (20%) were colonized by S. aureus, 32% of which were colonized by MRSA. Wound colonization by Staphylococcus spp. was associated with pneumonia or other respiratory disease (p = 0.03). Wound colonization by S. aureus was associated with nasal colonization by S. aureus (p < 0.001), fewer days of prior antibiotic use (p = 0.04), admission to a medical ward (p = 0.02), and age >65 years (p = 0.05). Among patients with wound colonization by MRSA, 37.50% had a history of prior antibiotic use, 75% had two or more comorbidities, 25% had cancer or diabetes, 50% had cardiovascular disease, and 50% died. Conclusions Wounds can be the source of Staphylococcus spp. infection, and high proportions of wounds are colonized by S. aureus and MRSA. Nasal colonization by S. aureus may be a source for wound colonization by S. aureus, illustrating the importance of preventing cross-contamination in hospital environments, especially among elderly patients. Wounds should be carefully managed to prevent microbial spread, thereby assisting patient recovery and reducing healthcare costs. PMID:24925025

Streptococcus mitis: walking the line between commensalism and pathogenesis.

PubMed

Mitchell, J

2011-04-01

Streptococcus mitis is a viridans streptococcus and a normal commensal of the human oropharynx. However, S. mitis can escape from this niche and cause a variety of infectious complications including infective endocarditis, bacteraemia and septicaemia. It uses a variety of strategies to effectively colonize the human oropharynx. These include expression of adhesins, immunoglobulin A proteases and toxins, and modulation of the host immune system. These various colonization factors allow S. mitis to compete for space and nutrients in the face of its more pathogenic oropharyngeal microbial neighbours. However, it is likely that in vulnerable immune-compromised patients S. mitis will use the same colonization and immune modulation factors as virulence factors promoting its opportunistic pathogenesis. The recent publication of a complete genome sequence for S. mitis strain B6 will allow researchers to thoroughly investigate which genes are involved in S. mitis host colonization and pathogenesis. Moreover, it will help to give insight into where S. mitis fits in the complicated oral microbiome. This review will discuss the current knowledge of S. mitis factors involved in host colonization, their potential role in virulence and what needs to be done to fully understand how a an oral commensal successfully transitions to a virulent pathogen. © 2011 John Wiley & Sons A/S.

Smad4 Inhibits VEGF-A and VEGF-C Expressions via Enhancing Smad3 Phosphorylation in Colon Cancer.

PubMed

Li, Xuemei; Li, Xinlei; Lv, Xiaohong; Xiao, Jianbing; Liu, Baoquan; Zhang, Yafang

2017-09-01

Smad4 is a critical factor in the TGF-β pathway and is involved in tumor progression and metastasis, but the role of Smad4 in colon cancer cells is unclear. The aim of this study is to explore the effect and the underlying mechanism of Smad4 on the growth, migration and apoptosis of colon cancer cells as well as vascular endothelial growth factor (VEGF)-A and VEGF-C secreted by these cells. In this study, we showed that Smad4, VEGF-A, and VEGF-C are independent prognostic factors of colon cancer, and Smad4 expression was negatively correlated with VEGF-A and -C in samples. We found that Smad4 mRNA and protein levels in colon cancer cells, particularly in HCT-116 cells, were significantly lower than those in the human intestinal epithelial cell line (HIEC). Smad4 overexpression promoted tumor cell apoptosis, inhibited VEGF-A and -C expression in vitro and in vivo, but had no effect on cell proliferation and migration. Tail vein injection of the virus inhibited xenograft growth in nude mice. Importantly, we also demonstrated that Smad4 could increase the phosphorylation level of Smad3, but not Smad2, which may be one of the mechanisms underlying these effects of Smad4 in colon cancer. Therefore, Smad4 may be a new target for the treatment of colon cancer. Anat Rec, 300:1560-1569, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The prognosis significance and application value of peritoneal elastic lamina invasion in colon cancer.

PubMed

Lu, Jun; Hu, Xiumei; Meng, Yutong; Zhao, Hongying; Cao, Qing; Jin, Mulan

2018-01-01

The aims of this study were to evaluate the associations between peritoneal elastic lamina invasion (ELI) and the clinicopathological prognostic factors of colon cancer, to evaluate the feasibility of ELI with use of an elastic stain to help diagnose serosal invasion of colon cancer in routine practice, so as to help us to provide a more accurate estimate for prognosis and stage of patients and a marker for postoperative treatment. 254 cases with colon cancer were included in the study. According to the presence of elastic lamina (EL) and elastic lamina invasion (ELI), all cases were divided into four groups: pT3 EL negative (pT3 EL (-)), pT3 ELI positive (pT3 ELI (+)), pT3 ELI negative (pT3 ELI (-)) and pT4a. Statistical analysis was used to analyze the relationship between elastic lamina invasion and other established adverse histologic features. The EL and ELI positive rates were 81.5% and 42.1% respectively. There were significant differences in mph node metastasis, venous invasion and tumor buds between pT3 ELI (-) and pT3 ELI (+), pT3 ELI (-) and pT4a. There was no significant difference in same factors between pT3 ELI (+) and pT4a. In pT3 stage, there were significant differences in lymph node metastasis, perineural invasion and tumor buds between EL (-) and ELI (+). There were no significant differences in same factors between EL (-) and ELI (-). EL was detected less frequently in right-sided tumors compared with left-sided tumors. ELI might be the prognostic factors of colon cancer with II stage and might be the marker of postoperative adjuvant chemotherapy. Patients with pT3 ELI (+) might have similar prognosis to patients with pT4a. For patients with pT3 colon cancer, EL(-) might have similar prognosis as ELI (-) and might take the same therapy. In addition, the right half colon EL positive rate was lower than the left colon. Elastic staining might be a useful tool to help determine the invasive depth and stage of colon cancer.

Induction of long term mucosal immunological memory in humans by an oral inactivated multivalent enterotoxigenic Escherichia coli vaccine.

PubMed

Lundgren, Anna; Jertborn, Marianne; Svennerholm, Ann-Mari

2016-06-08

We have evaluated the capacity of an oral multivalent enterotoxigenic Escherichia coli (ETEC) vaccine (MEV) to induce mucosal immunological memory. MEV consists of four inactivated E. coli strains over-expressing the major colonization factors (CFs) CFA/I, CS3, CS5 and CS6 and the LTB-related toxoid LCTBA. Memory responses were analyzed by comparing the magnitudes and kinetics of intestine-derived antibody-secreting cell responses to a single dose of MEV in three groups of adult Swedish volunteers (n=16-19 subjects per group) in a Phase I trial: non-immunized controls (I) and subjects who in a previous Phase I trial 13-23 months earlier had received two biweekly doses of MEV (II) or MEV+double mutant LT (dmLT) adjuvant (III). Responses against CFs and LTB were analyzed in antibodies in lymphocyte secretions (ALS) of blood mononuclear cells collected before (day 0) and 4/5 and 7 days after immunization. Specific circulating memory B cells present at the time of the single dose vaccination were also studied to determine if such cells may reflect mucosal memory. Considerably higher and significantly more frequent IgA ALS responses against all CFs and LTB were induced by the single vaccine dose in the previously immunized than in non-immunized volunteers. Furthermore, peak IgA ALS responses against all antigens were observed on days 4/5 in most of the previously immunized subjects whereas only a few previously non-vaccinated individuals responded before day 7. Priming with adjuvant did not influence memory responses. Circulating vaccine specific IgA memory B cells were not detected, whereas anti-toxin IgG memory B cells were identified 13-23 months after priming vaccination. We conclude that MEV induces functional mucosal immunological memory which remains at least 1-2 years. Furthermore, our results support that analysis of antibody-secreting cell responses after booster vaccination may be a useful approach to evaluate longstanding mucosal immunological memory in humans. ISRCTN27096290. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Patient Beliefs About Colon Cancer Screening.

PubMed

Ely, John W; Levy, Barcey T; Daly, Jeanette; Xu, Yinghui

2016-03-01

Only about half of eligible individuals undergo colon cancer screening. We have limited knowledge about the patient beliefs that adversely affect screening decisions and about which beliefs might be amenable to change through education. As part of a clinical trial, 641 rural Iowans, aged 52 to 79 years, reported their beliefs about colon cancer screening in response to a mailed questionnaire. Consenting subjects were randomized into four groups, which were distinguished by four levels of increasingly intensive efforts to promote screening. Two of the groups received mailed educational materials and completed a follow-up questionnaire, which allowed us to determine whether their beliefs about screening changed following the education. We also completed a factor analysis to identify underlying (latent) factors that might explain the responses to 33 questions about readiness, attitudes, and perceived barriers related to colon cancer screening. The strongest predictors of a patient's stated readiness to be screened were a physician's recommendation to be screened (1 point difference on 10-point Likert scale, 95 % confidence interval [CI], 0.5 to 1.6 point difference), a family history of colon cancer (0.85-point Likert scale difference, 95 % CI, 0.1 to 1.6), and a belief that health-care decisions should be mostly left to physicians rather than patients (Spearman correlation coefficient 0.21, P < .001). Of the 33 questionnaire items about screening beliefs, 11 (33 %) changed favorably following the educational intervention. In the factor analysis, the 33 items were reduced to 8 underlying factors, such as being too busy to undergo screening and worries about screening procedures. We found a limited number of underlying factors that may help explain patient resistance to colon cancer screening.

Protein kinase C βII and TGFβRII in ω-3 fatty acid–mediated inhibition of colon carcinogenesis

PubMed Central

Murray, Nicole R.; Weems, Capella; Chen, Lu; Leon, Jessica; Yu, Wangsheng; Davidson, Laurie A.; Jamieson, Lee; Chapkin, Robert S.; Thompson, E. Aubrey; Fields, Alan P.

2002-01-01

Încreasing evidence demonstrates that protein kinase C βII (PKCβII) promotes colon carcinogenesis. We previously reported that colonic PKCβII is induced during colon carcinogenesis in rodents and humans, and that elevated expression of PKCβII in the colon of transgenic mice enhances colon carcinogenesis. Here, we demonstrate that PKCβII represses transforming growth factor β receptor type II (TGFβRII) expression and reduces sensitivity to TGF-β–mediated growth inhibition in intestinal epithelial cells. Transgenic PKCβII mice exhibit hyperproliferation, enhanced colon carcinogenesis, and marked repression of TGFβRII expression. Chemopreventive dietary ω-3 fatty acids inhibit colonic PKCβII activity in vivo and block PKCβII-mediated hyperproliferation, enhanced carcinogenesis, and repression of TGFβRII expression in the colonic epithelium of transgenic PKCβII mice. These data indicate that dietary ω-3 fatty acids prevent colon cancer, at least in part, through inhibition of colonic PKCβII signaling and restoration of TGF-β responsiveness. PMID:12058013

Management of Colonic Volvulus

PubMed Central

Gingold, Daniel; Murrell, Zuri

2012-01-01

Colonic volvulus is a common cause of large bowel obstruction worldwide. It can affect all parts of the colon, but most commonly occurs in the sigmoid and cecal areas. This disease has been described for centuries, and was studied by Hippocrates himself. Currently, colonic volvulus is the third most common cause of large bowel obstruction worldwide, and is responsible for ∼15% of large bowel obstructions in the United States. This article will discuss the history of colonic volvulus, and the predisposing factors that lead to this disease. Moreover, the epidemiology and diagnosis of each type of colonic volvulus, along with the various treatment options will be reviewed. PMID:24294126

Staphylococcus aureus clonal dynamics and virulence factors in children with atopic dermatitis.

PubMed

Lomholt, Hans; Andersen, Klaus Ejner; Kilian, Mogens

2005-11-01

A prospective cohort study was undertaken to determine the clonal dynamics of Staphylococcus aureus colonization and infection during 1 y in children with atopic dermatitis, and to correlate specific clones, accessory gene regulator (agr) groups, and production of virulence factors with eczema activity. Eleven children were examined every 6 wk with swaps taken from active eczema, anterior nose, axillae and perineum, and scoring of eczema activity by severity scoring of atopic dermatitis (SCORAD). Individual S. aureus clonal types were identified and examined for production of superantigens, toxins, and were assigned to agr groups. S. aureus colonization patterns ranged from rare colonization over transient colonization to persistent colonization by a single clone or a dynamic exchange of up to five clones. Production of no single virulence factor including superantigens and toxins was significantly associated with exacerbation of eczema. In four children there was a shift between visits in agr group of colonizing clones. These shifts were associated with an increased SCORAD value of 19 (SE = 7, p = 0.009). Change of clones belonging to the same agr group was not associated with a higher SCORAD value. In 11 of 12 cases with two different clones co-colonizing a child the clones belonged to the same agr group. In conclusion, this limited group of children with atopic dermatitis showed highly variable colonization patterns of S. aureus, and communication between strains by use of agr encoded octa peptides appeared to be active in vivo. Increased severity of eczema was related to a change in agr group and may have been because of inflammation triggered by the takeover of an antigenically different clone, as agr groups represent ancient phylogenetic lineages.

Vibrio cholerae Colonization of Soft-Shelled Turtles

PubMed Central

Wang, Jiazheng; Yan, Meiying; Gao, He; Lu, Xin

2017-01-01

ABSTRACT Vibrio cholerae is an important human pathogen and environmental microflora species that can both propagate in the human intestine and proliferate in zooplankton and aquatic organisms. Cholera is transmitted through food and water. In recent years, outbreaks caused by V. cholerae-contaminated soft-shelled turtles, contaminated mainly with toxigenic serogroup O139, have been frequently reported, posing a new foodborne disease public health problem. In this study, the colonization by toxigenic V. cholerae on the body surfaces and intestines of soft-shelled turtles was explored. Preferred colonization sites on the turtle body surfaces, mainly the carapace and calipash of the dorsal side, were observed for the O139 and O1 strains. Intestinal colonization was also found. The colonization factors of V. cholerae played different roles in the colonization of the soft-shelled turtle's body surface and intestine. Mannose-sensitive hemagglutinin (MSHA) of V. cholerae was necessary for body surface colonization, but no roles were found for toxin-coregulated pili (TCP) or N-acetylglucosamine-binding protein A (GBPA). Both TCP and GBPA play important roles for colonization in the intestine, whereas the deletion of MSHA revealed only a minor colonization-promoting role for this factor. Our study demonstrated that V. cholerae can colonize the surfaces and the intestines of soft-shelled turtles and indicated that the soft-shelled turtles played a role in the transmission of cholera. In addition, this study showed that the soft-shelled turtle has potential value as an animal model in studies of the colonization and environmental adaption mechanisms of V. cholerae in aquatic organisms. IMPORTANCE Cholera is transmitted through water and food. Soft-shelled turtles contaminated with Vibrio cholerae (commonly the serogroup O139 strains) have caused many foodborne infections and outbreaks in recent years, and they have become a foodborne disease problem. Except for epidemiological investigations, no experimental studies have demonstrated the colonization by V. cholerae on soft-shelled turtles. The present studies will benefit our understanding of the interaction between V. cholerae and the soft-shelled turtle. We demonstrated the colonization by V. cholerae on the soft-shelled turtle's body surface and in the intestine and revealed the different roles of major V. cholerae factors for colonization on the body surface and in the intestine. Our work provides experimental evidence for the role of soft-shelled turtles in cholera transmission. In addition, this study also shows the possibility for the soft-shelled turtle to serve as a new animal model for studying the interaction between V. cholerae and aquatic hosts. PMID:28600312

Vibrio cholerae Colonization of Soft-Shelled Turtles.

PubMed

Wang, Jiazheng; Yan, Meiying; Gao, He; Lu, Xin; Kan, Biao

2017-07-15

Vibrio cholerae is an important human pathogen and environmental microflora species that can both propagate in the human intestine and proliferate in zooplankton and aquatic organisms. Cholera is transmitted through food and water. In recent years, outbreaks caused by V. cholerae -contaminated soft-shelled turtles, contaminated mainly with toxigenic serogroup O139, have been frequently reported, posing a new foodborne disease public health problem. In this study, the colonization by toxigenic V. cholerae on the body surfaces and intestines of soft-shelled turtles was explored. Preferred colonization sites on the turtle body surfaces, mainly the carapace and calipash of the dorsal side, were observed for the O139 and O1 strains. Intestinal colonization was also found. The colonization factors of V. cholerae played different roles in the colonization of the soft-shelled turtle's body surface and intestine. Mannose-sensitive hemagglutinin (MSHA) of V. cholerae was necessary for body surface colonization, but no roles were found for toxin-coregulated pili (TCP) or N -acetylglucosamine-binding protein A (GBPA). Both TCP and GBPA play important roles for colonization in the intestine, whereas the deletion of MSHA revealed only a minor colonization-promoting role for this factor. Our study demonstrated that V. cholerae can colonize the surfaces and the intestines of soft-shelled turtles and indicated that the soft-shelled turtles played a role in the transmission of cholera. In addition, this study showed that the soft-shelled turtle has potential value as an animal model in studies of the colonization and environmental adaption mechanisms of V. cholerae in aquatic organisms. IMPORTANCE Cholera is transmitted through water and food. Soft-shelled turtles contaminated with Vibrio cholerae (commonly the serogroup O139 strains) have caused many foodborne infections and outbreaks in recent years, and they have become a foodborne disease problem. Except for epidemiological investigations, no experimental studies have demonstrated the colonization by V. cholerae on soft-shelled turtles. The present studies will benefit our understanding of the interaction between V. cholerae and the soft-shelled turtle. We demonstrated the colonization by V. cholerae on the soft-shelled turtle's body surface and in the intestine and revealed the different roles of major V. cholerae factors for colonization on the body surface and in the intestine. Our work provides experimental evidence for the role of soft-shelled turtles in cholera transmission. In addition, this study also shows the possibility for the soft-shelled turtle to serve as a new animal model for studying the interaction between V. cholerae and aquatic hosts. Copyright © 2017 American Society for Microbiology.

Quantum dots targeted to vascular endothelial growth factor receptor 2 as a contrast agent for the detection of colorectal cancer

NASA Astrophysics Data System (ADS)

Carbary-Ganz, Jordan L.; Barton, Jennifer K.; Utzinger, Urs

2014-08-01

We successfully labeled colorectal cancer in vivo using quantum dots targeted to vascular endothelial growth factor receptor 2 (VEGFR2). Quantum dots with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking. The resulting QD655-VEGFR2 contrast agent was applied in vivo to the colon of azoxymethane (AOM) treated mice via lavage and allowed to incubate. The colons were then excised, cut longitudinally, opened to expose the lumen, and imaged en face using a fluorescence stereoscope. The QD655-VEGFR2 contrast agent produced a significant increase in contrast between diseased and undiseased tissues, allowing for fluorescence-based visualization of the diseased areas of the colon. Specificity was assessed by observing insignificant contrast increase when labeling colons of AOM-treated mice with quantum dots bioconjugated to isotype control antibodies, and by labeling the colons of saline-treated control mice. This contrast agent has a great potential for in vivo imaging of the colon through endoscopy.

Temperature-related risk factors associated with the colonization of broiler-chicken flocks with Campylobacter spp. in Iceland, 2001-2004

USDA-ARS?s Scientific Manuscript database

Our objective was to identify temperature-related risk factors associated with the colonization of broiler-chicken flocks with Campylobacter spp. in Iceland, with an underlying assumption that at minimum ambient temperatures, flies (Musca domestica) play a role in the epidemiology and seasonality of...

Rapid genetic typing of diarrheagenic Escherichia coli using a two-tube modified molecular beacon based multiplex real-time PCR assay and its clinical application

PubMed Central

2014-01-01

Background Diarrheagenic Escherichia coli (DEC), including Enterotoxigenic E.coli (ETEC), Enteroaggregative E.coli (EAEC), Enteropathogenic E.coli (EPEC), Enterohemolysin E.coli (EHEC) and Enteroinvasive E.coli (EIEC) causes diarrhea or hemolytic uremic syndromes among infants and travelers around the world. A rapid, reliable and repeatable method is urgent for identifying DEC so as to provide the reference for responding to diarrheal disease outbreak and the treatment of the diarrheal patients associated with DEC. Methods In this study, specific primers and modified molecular beacon probes of nine specific virulence genes, whose 5′end were added with homo tail sequence, were designed; and a two-tube modified molecular beacon based multiplex real–time PCR (rtPCR) assay for the identification of five Escherichia coli pathotypes, including ETEC, EAEC, EPEC, EHEC and EIEC was developed and optimized. Totally 102 bacterial strains, including 52 reference bacterial strains and 50 clinical strains were detected to confirm whether the target genes selected were specific. Then detection limits of the assay were tested. Lastly, the assay was applied to the detection of 11860 clinical samples to evaluate the specificity and sensitivity of the developed assay compared with the conventional PCR. Results The target genes were 100% specific as assessed on 102 bacterial strains since no cross-reactions were observed. The detection limits ranged from 88 CFU/mL (EHEC) to 880 CFU/mL (EPEC). Compared with the conventional PCR, the specificity and sensitivity of the multiplex rtPCR was 100% and over 99%, respectively. The coefficient of variation (CV) for each target gene ranged from 0.45% to 1.53%. 171 positive clinical samples were mostly identified as ETEC (n = 111, 64.9%) and EPEC (n = 38, 22.2%), which were the dominating pathotypes of DEC strains. Conclusion The developed multiplex rtPCR assay for the identification of DEC was high sensitive and specific and could be applied to the rapid identification of DEC in clinical and public health laboratories. PMID:25023669

Immunogenicity of recombinant Lactobacillus casei-expressing F4 (K88) fimbrial adhesin FaeG in conjunction with a heat-labile enterotoxin A (LTAK63) and heat-labile enterotoxin B (LTB) of enterotoxigenic Escherichia coli as an oral adjuvant in mice.

PubMed

Yu, M; Qi, R; Chen, C; Yin, J; Ma, S; Shi, W; Wu, Y; Ge, J; Jiang, Y; Tang, L; Xu, Y; Li, Y

2017-02-01

The aims of this study were to develop an effective oral vaccine against enterotoxigenic Escherichia coli (ETEC) infection and to design new and more versatile mucosal adjuvants. Genetically engineered Lactobacillus casei strains expressing F4 (K88) fimbrial adhesin FaeG (rLpPG-2-FaeG) and either co-expressing heat-labile enterotoxin A (LTA) subunit with an amino acid mutation associated with reduced virulence (LTAK63) and a heat-labile enterotoxin B (LTB) subunit of E. coli (rLpPG-2-LTAK63-co-LTB) or fused-expressing LTAK63 and LTB (rLpPG-2-LTAK63-fu-LTB) were constructed. The immunogenicity of rLpPG-2-FaeG in conjunction with rLpPG-2-LTAK63-co-LTB or rLpPG-2-LTAK63-fu-LTB as an orally administered mucosal adjuvant in mice was evaluated. Results showed that the levels of FaeG-specific serum IgG and mucosal sIgA, as well as the proliferation of lymphocytes, were significantly higher in mice orally co-administered rLpPG-2-FaeG and rLpPG-2-LTAK63-fu-LTB compared with those administered rLpPG-2-FaeG alone, and were lower than those co-administered rLpPG-2-FaeG and rLpPG-2-LTAK63-co-LTB. Moreover, effective protection was observed after challenge with F4+ ETEC strain CVCC 230 in mice co-administered rLpPG-2-FaeG and rLpPG-2-LTAK63-co-LTB or rLpPG-2-FaeG and rLpPG-2-LTAK63-fu-LTB group compared with those that received rLpPG-2-FaeG alone. rLpPG-2-FaeG showed greater immunogenicity in combination with LTAK63 and LTB as molecular adjuvants. Recombinant Lactobacillus provides a promising platform for the development of vaccines against F4+ ETEC infection. © 2016 The Society for Applied Microbiology.

Oxalobacter formigenes Colonization and Oxalate Dynamics in a Mouse Model

PubMed Central

Li, Xingsheng; Ellis, Melissa L.

2015-01-01

Animal and human studies have provided compelling evidence that colonization of the intestine with Oxalobacter formigenes reduces urinary oxalate excretion and lowers the risk of forming calcium oxalate kidney stones. The mechanism providing protection appears to be related to the unique ability of O. formigenes to rely on oxalate as a major source of carbon and energy for growth. However, much is not known about the factors that influence colonization and host-bacterium interactions. We have colonized mice with O. formigenes OxCC13 and systematically investigated the impacts of diets with different levels of calcium and oxalate on O. formigenes intestinal densities and urinary and intestinal oxalate levels. Measurement of intestinal oxalate levels in mice colonized or not colonized with O. formigenes demonstrated the highly efficient degradation of soluble oxalate by O. formigenes relative to other microbiota. The ratio of calcium to oxalate in diets was important in determining colonization densities and conditions where urinary oxalate and fecal oxalate excretion were modified, and the results were consistent with those from studies we have performed with colonized and noncolonized humans. The use of low-oxalate purified diets showed that 80% of animals retained O. formigenes colonization after a 1-week dietary oxalate deprivation. Animals not colonized with O. formigenes excreted two times more oxalate in feces than they had ingested. This nondietary source of oxalate may play an important role in the survival of O. formigenes during periods of dietary oxalate deprivation. These studies suggest that the mouse will be a useful model to further characterize interactions between O. formigenes and the host and factors that impact colonization. PMID:25979889

Prevalence of and Risk Factors for Multidrug-Resistant Acinetobacter baumannii Colonization Among High-Risk Nursing Home Residents

PubMed Central

Mody, Lona; Gibson, Kristen E.; Horcher, Amanda; Prenovost, Katherine; McNamara, Sara E.; Foxman, Betsy; Kaye, Keith S.; Bradley, Suzanne

2015-01-01

OBJECTIVE To characterize the epidemiology of multidrug-resistant (MDR) Acinetobacter baumannii colonization in high-risk nursing home (NH) residents. DESIGN Nested case-control study within a multicenter prospective intervention trial. SETTING Four NHs in Southeast Michigan. PARTICIPANTS Case patients and control subjects were NH residents with an indwelling device (urinary catheter and/or feeding tube) selected from the control arm of the Targeted Infection Prevention study. Cases were residents colonized with MDR (resistant to ≥3 classes of antibiotics) A. baumannii; controls were never colonized with MDR A. baumannii. METHODS For active surveillance cultures, specimens from the nares, oropharynx, groin, perianal area, wounds, and device insertion site(s) were collected upon study enrollment, day 14, and monthly thereafter. A. baumannii strains and their susceptibilities were identified using standard microbiologic methods. RESULTS Of 168 NH residents, 25 (15%) were colonized with MDR A. baumannii. Compared with the 143 controls, cases were more functionally disabled (Physical Self-Maintenance Score >24; odds ratio, 5.1 [95% CI, 1.8–14.9]; P < .004), colonized with Proteus mirabilis (5.8 [1.9–17.9]; P < .003), and diabetic (3.4 [1.2–9.9]; P < .03). Most cases (22 [88%]) were colonized with multiple antibiotic-resistant organisms and 16 (64%) exhibited co-colonization with at least one other resistant gram-negative bacteria. CONCLUSION Functional disability, P. mirabilis colonization, and diabetes mellitus are important risk factors for colonization with MDR A. baumannii in high-risk NH residents. A. baumannii exhibits widespread antibiotic resistance and a preference to colonize with other antibiotic-resistant organisms, meriting enhanced attention and improved infection control practices in these residents. PMID:26072936

Relationship between anthropometric factors, radiation exposure, and colon cancer incidence in the Life Span Study cohort of atomic bomb survivors.

PubMed

Semmens, Erin O; Kopecky, Kenneth J; Grant, Eric; Mathes, Robert W; Nishi, Nobuo; Sugiyama, Hiromi; Moriwaki, Hiroko; Sakata, Ritsu; Soda, Midori; Kasagi, Fumiyoshi; Yamada, Michiko; Fujiwara, Saeko; Akahoshi, Masazumi; Davis, Scott; Kodama, Kazunori; Li, Christopher I

2013-01-01

We examined colon cancer risk in atomic bomb survivors to investigate whether excess body weight after the bombings alters sensitivity to radiation effects. Of the 56,064 Japanese atomic bomb survivors with follow-up through 2002 with self-reported anthropometric data obtained from periodic mail surveys, 1,142 were diagnosed with colon cancer. We evaluated the influence of body mass index (BMI) and height on radiation-associated colon cancer risk using Poisson regression. We observed a similar linear dose-response relationship for the 56,064 subjects included in our analysis and the entire cohort of Japanese atomic bomb survivors [excess relative risk (ERR) per Gray (Gy) = 0.53, 95 % confidence interval (CI) 0.25-0.86]. Elevation in earliest reported BMI, BMI reported closest to colon cancer diagnosis, and time-varying BMI were associated with an elevated risk of colon cancer [relative risk (RR) per 5 kg/m(2) increase in BMI = 1.14, 95 % CI 1.03-1.26; RR = 1.16, 95 % CI 1.05-1.27; and RR = 1.15, 95 % CI 1.04-1.27, respectively]. Height was not significantly related to colon cancer risk. Inclusion of anthropometric variables in models had little impact on radiation risk estimates, and there was no evidence that sensitivity to the effect of radiation on colon cancer risk depended on BMI. Radiation exposure and BMI are both risk factors for colon cancer. BMI at various times after exposure to the atomic bombings does not significantly influence the relationship between radiation dose and colon cancer risk, suggesting that BMI and radiation impact colon cancer risk independently of each other.

Gender Difference and Dietary Supplemental Vitamin B6: Impact on Colon Luminal Environment.

PubMed

Nirmagustina, Dwi Eva; Yang, Yongshou; Kumrungsee, Thanutchaporn; Yanaka, Noriyuki; Kato, Norihisa

2018-01-01

Colon diseases can be affected by several factors such as gender difference and dietary supplemental vitamin B 6 (B 6 ). The nutritional status of B 6 is affected by gender difference, leading us to hypothesize that gender difference affects colon luminal environment, which is dependent on B 6 status. To investigate this hypothesis, we fed male and female rats a diet containing 1 mg, 7 mg, or 35 mg pyridoxine HCl/kg diet for 6 wk. We found significantly higher fecal mucin levels in female rats compared to those in male rats. Supplemental B 6 significantly increased fecal mucins and was particularly profound in the female rats. The abundances of cecal and fecal Akkermansia muciniphila (mucin degrader) were unaffected. The fecal mucin levels were significantly correlated with colonic free threonine and serine and with gene expression of colon MUC16, implying that the combined effect of gender and dietary B 6 on fecal mucins was mediated by the alteration in the levels of such amino acids and MUC16 expression. This study further showed the significant effects of gender difference on colonic free amino acids such as threonine, ornithine, asparagine/aspartate ratio, and glutamine/glutamate ratio, cecal and fecal Lactobacillus spp. levels, and colonic gene expressions of MUC16 and TLR8, the factors relating to colon health and diseases. Therefore, our findings suggest that gender difference and dietary B 6 may have an impact on colon diseases by modulating these parameters.

Risk factors for the development of active methicillin-resistant Staphylococcus aureus (MRSA) infection in patients colonized with MRSA at hospital admission.

PubMed

Cadena, Jose; Thinwa, Josephine; Walter, Elizabeth A; Frei, Christopher R

2016-12-01

Patients who present to Veterans Affairs hospitals are screened for methicillin-resistant Staphylococcus aureus (MRSA) colonization. Those who test positive are isolated during their hospital stay. However, it is unknown which of these patients are most likely to subsequently develop active MRSA infections. This retrospective case-control study characterized risk factors for active MRSA infection among patients colonized with MRSA at hospital admission. Potential demographic and clinical risk factors were identified using electronic queries and manual chart abstraction; data were compared by standard statistical tests, and variables with P ≤ .05 in bivariable analysis were entered into a multivariable logistic regression model. There were 71 cases and 213 controls. Risk factors associated with MRSA infection included diabetes mellitus with or without end organ damage (26% vs 14%, P = .02), hemiplegia (9% vs 2%, P = .01), chronic kidney disease (33% vs 20%, P = .03), postcolonization inpatient admission within 90 days (44% vs 29%, P = .03), surgery (41% vs 9%, P < .01), and dialysis (10% vs 3%, P = .02). On multivariable analysis, surgery during follow-up, dialysis during follow-up, and hemiplegia remained significant. Among patients with MRSA colonization, surgery or dialysis during follow-up and history of hemiplegia were associated with subsequent MRSA infection. Knowledge of these risk factors may allow for future targeted interventions to prevent MRSA infections among colonized patients. Published by Elsevier Inc.

Curcumin synergizes the growth inhibitory properties of Indian toad (Bufo melanostictus Schneider) skin-derived factor (BM-ANF1) in HCT-116 colon cancer cells.

PubMed

Giri, Biplab; Gomes, Antony; Sengupta, Radha; Banerjee, Sanjeev; Nautiyal, Jyoti; Sarkar, Fazlul H; Majumdar, Adhip P N

2009-01-01

Curcumin, an active ingredient of turmeric with no discernable toxicity, inhibits the growth of transformed cells and the development and progression of colon carcinogenesis in experimental animals. Recent data from one of our laboratories demonstrated that a crude skin extract or a purified crystalline compound (Bufo melanostictus-antineoplastic factor 1, BM-ANF1) from Indian common toad (Bufo melanostictus, Schneider) skin inhibits the growth of human leukemic cells. The present investigation was undertaken to determine whether combining BM-ANF1 with curcumin would be a better therapeutic strategy for colon cancer. Colon cancer HCT-116 cells were used. Changes in growth, apoptosis, growth factor receptor signaling and events of the cell cycle were analyzed. Curcumin together with BM-ANF1 produced a greater inhibition of HCT-116 cells growth than either agent alone, attributable to the inhibition of proliferation and stimulation of apoptosis, as evidenced by suppression of proliferating cell nuclear antigen (PCNA) expression, cell cycle arrest at the G2/M-phase and caspase-3 activation. There was also a marked reduction of cyclin-dependent kinase (CDK)2, CDK4 and cyclin B expression and up-regulation of CDK inhibitors (p21, p27) and p53, accompanied by attenuation of Akt signaling and nuclear factor-kappa B (NF-kappaB) activation. BM-ANF1 in combination with curcumin causes a marked inhibition of growth of colon cancer cells and could be an effective therapeutic strategy for colon cancer.

Gene expression patterns and dynamics of the colonization of common bean (Phaseolus vulgaris L.) by highly virulent and weakly virulent strains of Fusarium oxysporum

PubMed Central

Niño-Sánchez, Jonathan; Tello, Vega; Casado-del Castillo, Virginia; Thon, Michael R.; Benito, Ernesto P.; Díaz-Mínguez, José María

2015-01-01

The dynamics of root and hypocotyl colonization, and the gene expression patterns of several fungal virulence factors and plant defense factors have been analyzed and compared in the interaction of two Fusarium oxysporum f. sp. phaseoli strains displaying clear differences in virulence, with a susceptible common bean cultivar. The growth of the two strains on the root surface and the colonization of the root was quantitatively similar although the highly virulent (HV) strain was more efficient reaching the central root cylinder. The main differences between both strains were found in the temporal and spatial dynamics of crown root and hypocotyl colonization. The increase of fungal biomass in the crown root was considerably larger for the HV strain, which, after an initial stage of global colonization of both the vascular cylinder and the parenchymal cells, restricted its growth to the newly differentiated xylem vessels. The weakly virulent (WV) strain was a much slower and less efficient colonizer of the xylem vessels, showing also growth in the intercellular spaces of the parenchyma. Most of the virulence genes analyzed showed similar expression patterns in both strains, except SIX1, SIX6 and the gene encoding the transcription factor FTF1, which were highly upregulated in root crown and hypocotyl. The response induced in the infected plant showed interesting differences for both strains. The WV strain induced an early and strong transcription of the PR1 gene, involved in SAR response, while the HV strain preferentially induced the early expression of the ethylene responsive factor ERF2. PMID:25883592

Development of an Aotus nancymaae Model for Shigella Vaccine Immunogenicity and Efficacy Studies

PubMed Central

Gregory, Michael; Lugo-Roman, Luis A.; Galvez Carrillo, Hugo; Tilley, Drake Hamilton; Baldeviano, Christian; Simons, Mark P.; Reynolds, Nathanael D.; Ranallo, Ryan T.; Suvarnapunya, Akamol E.; Venkatesan, Malabi M.; Oaks, Edwin V.

2014-01-01

Several animal models exist to evaluate the immunogenicity and protective efficacy of candidate Shigella vaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenic Escherichia coli (ETEC) and Campylobacter spp. have been successfully developed with Aotus nancymaae, and the addition of a Shigella-Aotus challenge model would facilitate the testing of combination vaccines. A series of experiments were designed to identify the dose of Shigella flexneri 2a strain 2457T that induces an attack rate of 75% in the Aotus monkey. After primary challenge, the dose required to induce an attack rate of 75% was calculated to be 1 × 1011 CFU. Shigella-specific immune responses were low after primary challenge and subsequently boosted upon rechallenge. However, preexisting immunity derived from the primary challenge was insufficient to protect against the homologous Shigella serotype. A successive study in A. nancymaae evaluated the ability of multiple oral immunizations with live-attenuated Shigella vaccine strain SC602 to protect against challenge. After three oral immunizations, animals were challenged with S. flexneri 2a 2457T. A 70% attack rate was demonstrated in control animals, whereas animals immunized with vaccine strain SC602 were protected from challenge (efficacy of 80%; P = 0.05). The overall study results indicate that the Shigella-Aotus nancymaae challenge model may be a valuable tool for evaluating vaccine efficacy and investigating immune correlates of protection. PMID:24595138

YghJ, the secreted metalloprotease of pathogenic E. coli induces hemorrhagic fluid accumulation in mouse ileal loop.

PubMed

Tapader, Rima; Bose, Dipro; Pal, Amit

2017-04-01

YghJ, also known as SslE (Secreted and surface associated lipoprotein) is a cell surface associated and secreted lipoprotein harbouring M60 metalloprotease domain. Though the gene is known to be conserved among both pathogenic and commensal Escherichia coli isolates, the expression and secretion of YghJ was found to be higher among diverse E. coli pathotypes. YghJ, secreted from intestinal pathogens such as enterotoxigenic E. coli (ETEC) and enteropathogenic E. coli (EPEC) has been demonstrated to possess mucinase activity and hence facilitates colonization of these enteric pathogens to intestinal epithelial cells. Importantly, YghJ is also reported to be secreted from extraintestinal pathogenic E. coli isolates. In our previous study we have shown that YghJ, purified from a neonatal septicemic E. coli isolate could trigger induction of various proinflammatory cytokines in vitro. This led us to investigate the role of YghJ in causing in vivo tissue hemorrhage. In the present study, we validate the earlier in vitro finding and have showed that YghJ can cause extensive tissue damage in mouse ileum and is also able to induce significant fluid accumulation in a dose dependent manner in a mouse ileal loop (MIL) assay. Hence, our present study not only confirms the pathogenic potential of YghJ in sepsis pathophysiology but also indicates the enterotoxic ability of YghJ which makes it an important virulence determinant of intestinal pathogenic E. coli. Copyright © 2017 Elsevier Ltd. All rights reserved.

Colorectal Cancer and Alcohol Consumption—Populations to Molecules

PubMed Central

Rossi, Marco; Usman, Ahmad; Keshavarzian, Ali; Bishehsari, Faraz

2018-01-01

Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the third most common cancer diagnosed in both men and women in the world. Several environmental and habitual factors have been associated with the CRC risk. Alcohol intake, a common and rising habit of modern society, is one of the major risk factors for development of CRC. Here, we will summarize the evidence linking alcohol with colon carcinogenesis and possible underlying mechanisms. Some epidemiologic studies suggest that even moderate drinking increases the CRC risk. Metabolism of alcohol involves ethanol conversion to its metabolites that could exert carcinogenic effects in the colon. Production of ethanol metabolites can be affected by the colon microbiota, another recently recognized mediating factor to colon carcinogenesis. The generation of acetaldehyde and alcohol’s other metabolites leads to activation of cancer promoting cascades, such as DNA-adduct formation, oxidative stress and lipid peroxidation, epigenetic alterations, epithelial barrier dysfunction, and immune modulatory effects. Not only does alcohol induce its toxic effect through carcinogenic metabolites, but alcoholics themselves are predisposed to a poor diet, low in folate and fiber, and circadian disruption, which could further augment alcohol-induced colon carcinogenesis. PMID:29385712

Crystal structure of the Vibrio cholerae colonization factor TcpF and identification of a functional immunogenic site.

PubMed

Megli, Christina J; Yuen, Alex S W; Kolappan, Subramaniapillai; Richardson, Malcolm R; Dharmasena, Madushini N; Krebs, Shelly J; Taylor, Ronald K; Craig, Lisa

2011-06-03

Vibrio cholerae relies on two main virulence factors--toxin-coregulated pilus (TCP) and cholera toxin--to cause the gastrointestinal disease cholera. TCP is a type IV pilus that mediates bacterial autoagglutination and colonization of the intestine. TCP is encoded by the tcp operon, which also encodes TcpF, a protein of unknown function that is secreted by V. cholerae in a TCP-dependent manner. Although TcpF is not required for TCP biogenesis, a tcpF mutant has a colonization defect in the infant mouse cholera model that is as severe as a pilus mutant. Furthermore, TcpF antisera protect against V. cholerae infection. TcpF has no apparent sequence homology to any known protein. Here, we report the de novo X-ray crystal structure of TcpF and the identification of an epitope that is critical for its function as a colonization factor. A monoclonal antibody recognizing this epitope is protective against V. cholerae challenge and adds to the protection provided by an anti-TcpA antibody. These data suggest that TcpF has a novel function in V. cholerae colonization and define a region crucial for this function. Copyright © 2011 Elsevier Ltd. All rights reserved.

Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue-Yamauchi, Akane, E-mail: ainoyama@research.twmu.ac.jp; Oda, Hideaki

2012-04-27

Highlights: Black-Right-Pointing-Pointer DRP1 is required for mitochondrial fission in colon cancer cells. Black-Right-Pointing-Pointer DRP1 participates in inhibition of colon cancer cell apoptosis. Black-Right-Pointing-Pointer DRP1 can inhibit apoptosis through the regulation of cytochrome c release. -- Abstract: Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116more » and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.« less

Prevalence and Risk Factors of Colonization with Staphylococcus aureus in Healthy Pet Cats Kept in the City Households

PubMed Central

Płoneczka-Janeczko, Katarzyna; Rypuła, Krzysztof

2016-01-01

Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a significant pathogen in both human medicine and veterinary medicine. The importance of pets as reservoirs of human infections is still poorly understood. This article provides detailed information of a cross-sectional study of a S. aureus colonization in clinically healthy indoor cats. The study systematically assessed a number of different anatomical locations for the S. aureus colonization and the influence of a range of potential risk factors on the value of the final S. aureus colonization rate. The incidence rates observed for cats with at least one site positive for S. aureus or MRSA were 17.5% and 6.63%, respectively. The following risk factors were identified: one or more owners working in the healthcare industry (human or veterinary); dogs being kept with the cat under investigation; treatment of the cat under investigation with antibiotics or chemotherapeutics during the previous year. In conclusion, this study revealed a higher prevalence of MRSA than what has previously been reported in healthy pets. A combination of anatomical locations from which the samples were collected had a major influence on the final value of the S. aureus colonization rate. PMID:27766257

Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut.

PubMed

Roager, Henrik M; Hansen, Lea B S; Bahl, Martin I; Frandsen, Henrik L; Carvalho, Vera; Gøbel, Rikke J; Dalgaard, Marlene D; Plichta, Damian R; Sparholt, Morten H; Vestergaard, Henrik; Hansen, Torben; Sicheritz-Pontén, Thomas; Nielsen, H Bjørn; Pedersen, Oluf; Lauritzen, Lotte; Kristensen, Mette; Gupta, Ramneek; Licht, Tine R

2016-06-27

Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites. Additionally, shorter colonic transit time correlates with metabolites possibly reflecting increased renewal of the colonic mucosa. Together, this suggests that a high gut microbial richness does not per se imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.

Korean Solar Salt Ameliorates Colon Carcinogenesis in an AOM/DSS-Induced C57BL/6 Mouse Model.

PubMed

Ju, Jaehyun; Kim, Yeung-Ju; Park, Eui Seong; Park, Kun-Young

2017-06-01

The effects of Korean solar salt on an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer C57BL/6 mouse model were studied. Korean solar salt samples (SS-S, solar salt from S salt field; SS-Yb, solar salt from Yb salt field), nine-time-baked bamboo salt (BS-9x, made from SS-Yb), purified salt (PS), and SS-G (solar salt from Guérande, France) were orally administered at a concentration of 1% during AOM/DSS colon cancer induction, and compared for their protective effects during colon carcinogenesis in C57BL/6 mice. SS-S and SS-Yb suppressed colon length shortening and tumor counts in mouse colons. Histological evaluation by hematoxylin and eosin staining also revealed suppression of tumorigenesis by SS-S. Conversely, PS and SS-G did not show a similar suppressive efficacy as Korean solar salt. SS-S and SS-Yb promoted colon mRNA expression of an apoptosis-related factor and cell-cycle-related gene and suppressed pro-inflammatory factor. SS-Yb baked into BS-9x further promoted these anti-carcinogenic efficacies. Taken together, the results indicate that Korean solar salt, especially SS-S and SS-Yb, exhibited anti-cancer activity by modulating apoptosis- and inflammation-related gene expression during colon carcinogenesis in mice, and bamboo salt baked from SS-Yb showed enhanced anti-cancer functionality.

Colon-targeted oral drug delivery systems: design trends and approaches.

PubMed

Amidon, Seth; Brown, Jack E; Dave, Vivek S

2015-08-01

Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

Expression of accessory colonization factor subunit A (ACFA) of Vibrio cholerae and ACFA fused to cholera toxin B subunit in transgenic tomato (Solanum lycopersicum).

PubMed

Sharma, Manoj Kumar; Jani, Dewal; Thungapathra, M; Gautam, J K; Meena, L S; Singh, Yogendra; Ghosh, Amit; Tyagi, Akhilesh Kumar; Sharma, Arun Kumar

2008-05-20

In earlier study from our group, cholera toxin B subunit had been expressed in tomato for developing a plant-based vaccine against cholera. In the present investigation, gene for accessory colonization factor (acf) subunit A, earlier reported to be essential for efficient colonization in the intestine, has been expressed in Escherichia coli as well as tomato plants. Gene encoding for a chimeric protein having a fusion of cholera toxin B subunit and accessory colonization factor A was also expressed in tomato to generate more potent combinatorial antigen. CaMV35S promoter with a duplicated enhancer sequence was used for expression of these genes in tomato. Integration of transgenes into tomato genome was confirmed by PCR and Southern hybridization. Expression of the genes was confirmed at transcript and protein levels. Accessory colonization factor A and cholera toxin B subunit fused to this protein accumulated up to 0.25% and 0.08% of total soluble protein, respectively, in the fruits of transgenic plants. Whereas protein purified from E. coli, in combination with cholera toxin B subunit can be used for development of conventional subunit vaccine, tomato fruits expressing these proteins can be used together with tomato plants expressing cholera toxin B subunit for development of oral vaccine against cholera.

A Murine Model of Group B Streptococcus Vaginal Colonization.

PubMed

Patras, Kathryn A; Doran, Kelly S

2016-11-16

Streptococcus agalactiae (group B Streptococcus, GBS), is a Gram-positive, asymptomatic colonizer of the human gastrointestinal tract and vaginal tract of 10 - 30% of adults. In immune-compromised individuals, including neonates, pregnant women, and the elderly, GBS may switch to an invasive pathogen causing sepsis, arthritis, pneumonia, and meningitis. Because GBS is a leading bacterial pathogen of neonates, current prophylaxis is comprised of late gestation screening for GBS vaginal colonization and subsequent peripartum antibiotic treatment of GBS-positive mothers. Heavy GBS vaginal burden is a risk factor for both neonatal disease and colonization. Unfortunately, little is known about the host and bacterial factors that promote or permit GBS vaginal colonization. This protocol describes a technique for establishing persistent GBS vaginal colonization using a single β-estradiol pre-treatment and daily sampling to determine bacterial load. It further details methods to administer additional therapies or reagents of interest and to collect vaginal lavage fluid and reproductive tract tissues. This mouse model will further the understanding of the GBS-host interaction within the vaginal environment, which will lead to potential therapeutic targets to control maternal vaginal colonization during pregnancy and to prevent transmission to the vulnerable newborn. It will also be of interest to increase our understanding of general bacterial-host interactions in the female vaginal tract.

[Drug related colonic perforation: Case report].

PubMed

Núñez-García, Edgar; Valencia-García, Luis César; Sordo-Mejía, Ricardo; Kajomovitz-Bialostozky, Daniel; Chousleb-Kalach, Alberto

2016-01-01

Acute pseudo-obstruction of the colon is a disorder characterised by an increase in intra-luminal pressure that leads to ischaemia and necrosis of the intestinal wall. The mechanism that produces the lesion is unknown, although it has been associated with: trauma, anaesthesia, or drugs that alter the autonomic nervous system. The pathophysiology of medication induced colon toxicity can progress to a perforated colon and potentially death. Present a case of a colonic pseudo-obstruction in a patient with polypharmacy as the only risk factor and to review the medical literature related to the treatment of this pathology. The case is presented of a 67 year old woman with colonic pseudo-obstruction who presented with diffuse abdominal pain and distension. The pain progressed and reached an intensity of 8/10, and was accompanied by fever and tachycardia. There was evidence of free intraperitoneal air in the radiological studies. The only risk factor was the use of multiple drugs. The colonic pseudo-obstruction progressed to intestinal perforation, requiring surgical treatment, which resolved the problem successfully. It is important to consider drug interaction in patients with multiple diseases, as it may develop complications that can be avoided if detected on time. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Polarization of macrophages in the tumor microenvironment is influenced by EGFR signaling within colon cancer cells

PubMed Central

Zhang, Weina; Chen, Lechuang; Ma, Kai; Zhao, Yahui; Liu, Xianghe; Wang, Yu; Liu, Mei; Liang, Shufang; Zhu, Hongxia; Xu, Ningzhi

2016-01-01

Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4. By contrast, conditioned medium of EGFR knockout colon cancer cells inhibited expression of these M2-related markers and induced macrophage expression of the M1-related markers inducible nitric oxide synthase (iNOS), IL-12, TNF-α and CCR7. EGFR knockout in colon cancer cells inhibited macrophage-induced promotion of xenograft tumor growth. Moreover, colon cancer-derived insulin-like growth factor-1 (IGF-1) increased Arg1 expression, and treatment with the IGF1R inhibitor AG1024 inhibited that increase. These results suggest that inhibition of EGFR signaling in colon cancer cells modulates cytokine secretion (e.g. IGF-1) and prevents M1-to-M2 macrophage polarization, thereby inhibiting cancer cell growth. PMID:27683110

Beliefs about causes of colon cancer by English-as-a-Second-Language Chinese immigrant women to Canada.

PubMed

McWhirter, Jennifer Elizabeth; Todd, Laura E; Hoffman-Goetz, Laurie

2011-12-01

Colon cancer is the second leading cause of cancer death for Canadians. Immigrants underutilize screening and may be at greater risk of late stage diagnosis and death from the disease. This mixed-methods study investigated the self-reported causes of colon cancer by 66 English-as-a-Second-Language Chinese immigrant women to Canada after reading a fact sheet which listed two causes of colon cancer (polyps and cause unknown) and six ways to help prevent colon cancer (lifestyle, diet, weight, smoking, alcohol, and screening). Women correctly named or described both causes (6.1%) or one cause (22.7%), could not name or describe either cause (19.7%), or named or described causes not included on the fact sheet (54.5%). The most common causes reported by participants were "risk factors": diet (53.0%), family history (28.8%), and lifestyle (22.7%). Women confused cause with risk factor and infrequently mentioned screening. Possible reasons for their reported beliefs are discussed.

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains

PubMed Central

Godwin, Heather; Pill, Gemma; Mbuvi, Emily; Vaughan, Alison; Griffiths, David; Martin, Jessica; Fawley, Warren; Dingle, Kate E.; Oakley, Sarah; Wanelik, Kazimierz; Finney, John M.; Kachrimanidou, Melina; Moore, Catrin E.; Gorbach, Sherwood; Riley, Thomas V.; Crook, Derrick W.; Peto, Tim E. A.; Wilcox, Mark H.; Walker, A. Sarah

2017-01-01

Background Approximately 30–40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. Methods Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases. Results 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0–10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%). Conclusions In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread. PMID:28813461

Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor

PubMed Central

Wang, Lihong; Liu, Liping; Shi, Yan; Cao, Hanwei; Chaturvedi, Rupesh; Calcutt, M. Wade; Hu, Tianhui; Ren, Xiubao; Wilson, Keith T.; Polk, D. Brent; Yan, Fang

2012-01-01

Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the mouse immorto-Min colonic epithelial (IMCE) cells carrying the Apc min mutation, and of normal colon epithelial cells, namely young adult mouse colonic epithelium (YAMC) cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF) release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth. PMID:22574158

Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

PubMed Central

2011-01-01

Background Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent. PMID:21864401

ICU Acquisition Rate, Risk Factors, and Clinical Significance of Digestive Tract Colonization With Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis.

PubMed

Detsis, Marios; Karanika, Styliani; Mylonakis, Eleftherios

2017-04-01

To evaluate the acquisition rate, identify risk factors, and estimate the risk for subsequent infection, associated with the colonization of the digestive tract with extended-spectrum beta-lactamase-producing Enterobacteriaceae during ICU-hospitalization. PubMed, EMBASE, and reference lists of all eligible articles. Included studies provided data on ICU-acquired colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae in previously noncolonized and noninfected patients and used the double disk synergy test for extended-spectrum beta-lactamase-producing Enterobacteriaceae phenotypic confirmation. Studies reporting extended-spectrum beta-lactamase-producing Enterobacteriaceae outbreaks or data on pediatric population were excluded. Two authors independently assessed study eligibility and performed data extraction. Thirteen studies (with 15,045 ICUs-patients) were evaluated using a random-effect model and a meta-regression analysis. The acquisition rate of digestive tract colonization during ICU stay was 7% (95% CI, 5-10) and it varies from 3% (95% CI, 2-4) and 4% (95% CI, 2-6) in the Americas and Europe to 21% (95% CI, 9-35) in the Western Pacific region. Previous hospitalization (risk ratio, 1.57 [95% CI, 1.07-2.31]) or antibiotic use (risk ratio, 1.65 [95% CI, 1.15-2.37]) and exposure to beta-lactams/beta-lactamase inhibitors (risk ratio, 1.78 [95% CI, 1.24-2.56]) and carbapenems (risk ratio, 2.13 [95% CI, 1.49-3.06]) during the ICU stay were independent risk factors for ICU-acquired colonization. Importantly, colonized patients were more likely to develop an extended-spectrum beta-lactamase-producing Enterobacteriaceae infection (risk ratio, 49.62 [95% CI, 20.42-120.58]). The sensitivity and specificity of prior colonization to predict subsequent extended-spectrum beta-lactamase-producing Enterobacteriaceae infection were 95.1% (95% CI, 54.7-99.7) and 89.2% (95% CI, 77.2-95.3), respectively. The ICU acquisition rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae ranged from 5% to 10%. Previous use of beta-lactam/beta-lactamase or carbapenems and recent hospitalization were independent risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae colonization, and colonization was associated with significantly higher frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae subsequent infection and increased mortality.

Genotypic and Phenotypic Characterization of Enterotoxigenic Escherichia coli Strains Isolated from Peruvian Children

DTIC Science & Technology

2010-09-01

Organization (WHO), ETEC is the second most common cause of diarrhea after rotavirus in children less than 5 years of age and is therefore an...pathogens (Shigella, Salmonella. Vibrio, Campylo/Jacter, Gi- ardia Iamblia, Cryptosporidium, and rotavirus ) by conventional methods. Five lactose...DAEC (2% and 3%, respec- tively), Campylobacter (20% and 6%, respectively), and Shi- gella (2% and 0%, respectively). Rotavirus was found in 10% ( 4

Unsealed Tubewells Lead to Increased Fecal Contamination of Drinking Water

PubMed Central

Knappett, Peter S. K.; McKay, Larry D.; Layton, Alice; Williams, Daniel E.; Alam, Md. J.; Mailloux, Brian J.; Ferguson, Andrew S.; Culligan, Patricia J.; Serre, Marc L.; Emch, Michael; Ahmed, Kazi M.; Sayler, Gary S.; van Geen, Alexander

2013-01-01

Bangladesh is underlain by shallow aquifers in which millions of drinking water wells are emplaced without annular seals. Fecal contamination has been widely detected in private tubewells. To evaluate the impact of well construction on microbial water quality 35 private tubewells (11 with intact cement platforms, 19 without) and 17 monitoring wells (11 with the annulus sealed with cement, 6 unsealed) were monitored for cultured E. coli over 18 months. Additionally, two “snap shot” sampling events were performed on a subset of wells during late-dry and early-wet seasons, wherein the fecal indicator bacteria (FIB) E. coli, Bacteroidales and the pathogenicity genes eltA (ETEC E. coli), ipaH (Shigella) and 40/41 hexon (adenovirus) were detected using qPCR. No difference in E. coli detection frequency was found between tubewells with and without platforms. Unsealed private wells, however, contained cultured E. coli more frequently and higher concentrations of FIB than sealed monitoring wells (p<0.05), suggestive of rapid downward flow along unsealed annuli. As a group the pathogens ETEC, Shigella and adenovirus were detected more frequently (10/22) during the wet season than the dry season (2/20). This suggests proper sealing of private tubewell annuli may lead to substantial improvements in microbial drinking water quality. PMID:23165714

DNA sequence analysis of the composite plasmid pTC conferring virulence and antimicrobial resistance for porcine enterotoxigenic Escherichia coli.

PubMed

Fekete, Péter Z; Brzuszkiewicz, Elzbieta; Blum-Oehler, Gabriele; Olasz, Ferenc; Szabó, Mónika; Gottschalk, Gerhard; Hacker, Jörg; Nagy, Béla

2012-01-01

In this study the plasmid pTC, a 90 kb self-conjugative virulence plasmid of the porcine enterotoxigenic Escherichia coli (ETEC) strain EC2173 encoding the STa and STb heat-stable enterotoxins and tetracycline resistance, has been sequenced in two steps. As a result we identified five main distinct regions of pTC: (i) the maintenance region responsible for the extreme stability of the plasmid, (ii) the TSL (toxin-specific locus comprising the estA and estB genes) which is unique and characteristic for pTC, (iii) a Tn10 transposon, encoding tetracycline resistance, (iv) the tra (plasmid transfer) region, and (v) the colE1-like origin of replication. It is concluded that pTC is a self-transmissible composite plasmid harbouring antibiotic resistance and virulence genes. pTC belongs to a group of large conjugative E. coli plasmids represented by NR1 with a widespread tra backbone which might have evolved from a common ancestor. This is the first report of a completely sequenced animal ETEC virulence plasmid containing an antimicrobial resistance locus, thereby representing a selection advantage for spread of pathogenicity in the presence of antimicrobials leading to increased disease potential. Copyright © 2011. Published by Elsevier GmbH.

[Efficacy of disinfection treatments using essential oils and ultrasound on tomato fruits inoculated with Escherichia coli and impact on antioxidant activity].

PubMed

Luna Guevara, María L; Luna Guevara, Juan J; Ruiz Espinosa, Héctor; Leyva Abascal, Lucero; Díaz González, Carolina B

2015-01-01

Fresh produce often harbors a great number of microorganisms; hence, its growing demand may constitute a risk for consumers. The aim of this study was to evaluate the efficacy of several disinfection procedures against enterotoxigenic Escherichia coli (ETEC) inoculated on tomato fruits and the conservation of the antioxidant properties of these disinfected fruits. Fruits were immersed for 5 or 10min in oregano or thyme essential oil dispersions (5, 10ppm), with or without ultrasound treatment. Antioxidant activity of disinfected fruits was determined as the ability to scavenge 2,2-diphenyl-1-pricrylhydrazyl (DPPH) radicals and was reported as percentage of inhibition (%I). The most efficient disinfectant treatments showing significant differences (p≤.05) between the reductions log10 CFU/g (S) of ETEC were those using 10ppm oregano for 10min, with S=3.05 in individual treatments and S=4.03 in mixed treatments. The highest %I was obtained with individual sonication treatments (69.52 and 72.48), while in combined treatments the %I values increased with thyme oil 5ppm and ultrasound for 5min (51.27%) and 10min (53.31%). Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

The discovery of cholera - like enterotoxins produced by Escherichia coli causing secretory diarrhoea in humans

PubMed Central

Sack, R. Bradley

2011-01-01

Non-vibrio cholera has been recognized as a clinical entity for as long as cholera was known to be caused by Vibrio cholerae. Until 1968, the aetiologic agent of this syndrome was not known. Following a series of studies in patients with non-vibrio cholera it was found that these patients had large concentrations of Escherichia coli in the small bowel and stools which produced cholera toxin-like enterotoxins, and had fluid and electrolyte transport abnormalities in the small bowel similar to patients with documented cholera. Furthermore, these patients developed antibodies to the cholera-like enterotoxin. Later studies showed that these strains, when fed to volunteers produced a cholera-like disease and that two enterotoxins were found to be produced by these organisms: a heat-labile enterotoxin (LT) which is nearly identical to cholera toxin, and a heat-stable enterotoxin (ST), a small molecular weight polypeptide. E. coli that produced one or both of these enterotoxins were designated enterotoxigenic E. coli (ETEC). ETEC are now known not only to cause a severe cholera-like illness, but to be the most common bacterial cause of acute diarrhoea in children in the developing world, and to be the most common cause of travellers’ diarrhoea in persons who visit the developing world. PMID:21415491

Unsealed tubewells lead to increased fecal contamination of drinking water.

PubMed

Knappett, Peter S K; McKay, Larry D; Layton, Alice; Williams, Daniel E; Alam, Md J; Mailloux, Brian J; Ferguson, Andrew S; Culligan, Patricia J; Serre, Marc L; Emch, Michael; Ahmed, Kazi M; Sayler, Gary S; van Geen, Alexander

2012-12-01

Bangladesh is underlain by shallow aquifers in which millions of drinking water wells are emplaced without annular seals. Fecal contamination has been widely detected in private tubewells. To evaluate the impact of well construction on microbial water quality 35 private tubewells (11 with intact cement platforms, 19 without) and 17 monitoring wells (11 with the annulus sealed with cement, six unsealed) were monitored for culturable Escherichia coli over 18 months. Additionally, two 'snapshot' sampling events were performed on a subset of wells during late-dry and early-wet seasons, wherein the fecal indicator bacteria (FIB) E. coli, Bacteroidales and the pathogenicity genes eltA (enterotoxigenic E. coli; ETEC), ipaH (Shigella) and 40/41 hexon (adenovirus) were detected using quantitative polymerase chain reaction (qPCR). No difference in E. coli detection frequency was found between tubewells with and without platforms. Unsealed private wells, however, contained culturable E. coli more frequently and higher concentrations of FIB than sealed monitoring wells (p < 0.05), suggestive of rapid downward flow along unsealed annuli. As a group the pathogens ETEC, Shigella and adenovirus were detected more frequently (10/22) during the wet season than the dry season (2/20). This suggests proper sealing of private tubewell annuli may lead to substantial improvements in microbial drinking water quality.

Pathogenic bacteria induce colonic PepT1 expression: an implication in host defense response

PubMed Central

Nguyen, Hang Thi Thu; Dalmasso, Guillaume; Powell, Kimberly R.; Yan, Yutao; Bhatt, Shantanu; Kalman, Daniel; Sitaraman, Shanthi; Merlin, Didier

2009-01-01

Background & Aims Expression of the di/tripeptide transporter PepT1 has been observed in the colon under inflammatory conditions, however, the inducing factors and underlying mechanisms remain unknown. Here, we address the effects of pathogenic bacteria on colonic PepT1 expression together with its functional consequences. Methods Human colonic HT29-Cl.19A cells were infected with the attaching and effacing (A/E) enteropathogenic E. coli (EPEC). Wild-type and PepT1 transgenic mice or cultured colonic tissues derived from these mice were infected with Citrobacter rodentium, a murine A/E pathogen related to EPEC. Results EPEC induced PepT1 expression and activity in HT29-Cl.19A cells by intimately attaching to host cells through lipid rafts. Induction of PepT1 expression by EPEC required the transcription factor Cdx2. PepT1 expression reduced binding of EPEC to lipid rafts, as well as activation of NF-κB and MAP kinase and production of IL-8. Accordingly, ex vivo and in vivo experiments revealed that C. rodentium induced colonic PepT1 expression and that, compared to their wild-type counterparts, PepT1 transgenic mice infected with C. rodentium exhibited decreased bacterial colonization, production of pro-inflammatory cytokines, and neutrophil infiltration into the colon. Conclusions Our findings demonstrate a molecular mechanism underlying the regulation of colonic PepT1 expression under pathological conditions and reveal a novel role for PepT1 in host defense via its capacity to modulate bacterial-epithelial interactions and intestinal inflammation. PMID:19549526

Is it worth screening for vancomycin-resistant Enterococcus faecium colonization?: Financial burden of screening in a developing country.

PubMed

Ulu-Kilic, Aysegul; Özhan, Esra; Altun, Dilek; Perçin, Duygu; Güneş, Tamer; Alp, Emine

2016-04-01

The screening of critically ill patients at high risk of vancomycin resistant enterococci (VRE) colonization, to detect and isolate colonized patients, is recommended to prevent and control the transmission of VRE. Screening asymptomatic carriers brings financial burden for institutions. In this study, we performed risk analysis for VRE colonization and determined the financial burden of screening in a middle-income country, Turkey. We retrospectively analyzed the VRE surveillance data from a pediatric hospital between 2010 and 2014. A case-control study was conducted to identify the risk factors of colonization. Total cost of VRE screening and additional costs for a VRE colonized patient (including active surveillance cultures and contact isolation) were calculated. During the 4-year period, 6,372 patients were screened for perirectal VRE colonization. The rate of culture-positive specimens among all patients screened was 239 (3.75%). The rate of VRE infection was 0.04% (n = 3) among all patients screened. Length of hospital stay, malignancy, and being transferred from another institution were independently associated risk factors for colonization. Annual estimated costs for the laboratory were projected as $19,074 (76,295/4) for all patients screened. Cost of contact isolation for each patient colonized in a ward and an intensive care unit was $270 and $718, respectively. In developing countries, institutions should identify their own high-risk patients; screening priorities should be based on prevalence of infection and hospital financial resources. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Applicability of an established management algorithm for destructive colon injuries after abbreviated laparotomy: a 17-year experience.

PubMed

Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Shahan, Charles P; Cullinan, Darren R; Marino, Katy A; Fabian, Timothy C; Croce, Martin A

2014-04-01

For more than a decade, operative decisions (resection plus anastomosis vs diversion) for colon injuries, at our institution, have followed a defined management algorithm based on established risk factors (pre- or intraoperative transfusion requirements of more than 6 units packed RBCs and/or presence of significant comorbid diseases). However, this management algorithm was originally developed for patients managed with a single laparotomy. The purpose of this study was to evaluate the applicability of this algorithm to destructive colon injuries after abbreviated laparotomy (AL) and to determine whether additional risk factors should be considered. Consecutive patients over a 17-year period with colon injuries after AL were identified. Nondestructive injuries were managed with primary repair. Destructive wounds were resected at the initial laparotomy followed by either a staged diversion (SD) or a delayed anastomosis (DA) at the subsequent exploration. Outcomes were evaluated to identify additional risk factors in the setting of AL. We identified 149 patients: 33 (22%) patients underwent primary repair at initial exploration, 42 (28%) underwent DA, and 72 (49%) had SD. Two (1%) patients died before re-exploration. Of those undergoing DA, 23 (55%) patients were managed according to the algorithm and 19 (45%) were not. Adherence to the algorithm resulted in lower rates of suture line failure (4% vs 32%, p = 0.03) and colon-related morbidity (22% vs 58%, p = 0.03) for patients undergoing DA. No additional specific risk factors for suture line failure after DA were identified. Adherence to an established algorithm, originally defined for destructive colon injuries after single laparotomy, is likewise efficacious for the management of these injuries in the setting of AL. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion.

PubMed

Belo, Angelica; Cheng, Kunrong; Chahdi, Ahmed; Shant, Jasleen; Xie, Guofeng; Khurana, Sandeep; Raufman, Jean-Pierre

2011-05-01

Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion.

Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion

PubMed Central

Belo, Angelica; Cheng, Kunrong; Chahdi, Ahmed; Shant, Jasleen; Xie, Guofeng; Khurana, Sandeep

2011-01-01

Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion. PMID:21273532

Active case finding for carbapenemase-producing Enterobacteriaceae in a teaching hospital: prevalence and risk factors for colonization.

PubMed

Poole, K; George, R; Decraene, V; Shankar, K; Cawthorne, J; Savage, N; Welfare, W; Dodgson, A

2016-10-01

Over the past decade, the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) has increased. Whilst basic infection prevention and control practices reduce the risk of transmission, cases of unrecognized carriage pose a potential risk of transmission. To estimate the prevalence of CPE and explore risk factors associated with colonization within a large teaching hospital with an established CPE outbreak. All inpatients that had not previously tested positive for CPE were offered testing. Demographic and hospital episode data were also collected, together with antibiotic and proton pump inhibitor (PPI) use in the preceding 24h. This study identified 70 CPE-positive cases (26 newly identified and 44 previously known) and 592 CPE-negative cases, giving a combined prevalence of 11% [95% confidence interval (CI) 8-13]. Medication (antibiotic and PPI use), previous admission, ethnicity and length of stay were assessed as risk factors for colonization, and none were found to be independently associated with CPE colonization. Using logistic regression, age [odds ratio (OR) 1.03, 95% CI 1.01-1.07] and antibiotic use (OR 2.55, 95% CI 1.08-6.03) were the only risk factors significantly associated with CPE colonization. This study has added to the evidence base by estimating the prevalence of CPE among inpatients in an acute hospital with an established CPE outbreak. A case-finding exercise was feasible and identified a number of new cases. Despite a small sample size, increasing age and prescription of an antibiotic on the day of testing were significantly associated with CPE colonization. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

The mother as most important risk factor for colonization of very low birth weight (VLBW) infants with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E).

PubMed

Denkel, Luisa A; Schwab, Frank; Kola, Axel; Leistner, Rasmus; Garten, Lars; von Weizsäcker, Katharina; Geffers, Christine; Gastmeier, Petra; Piening, Brar

2014-08-01

This study aimed to determine the prevalence of and risk factors for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and methicillin-resistant Staphylococcus aureus (MRSA) in very low birth weight (VLBW; <1500 g) infants and their mothers. This investigation was conducted in the perinatal centre at the Charité Berlin between May 2012 and June 2013. VLBW infants and their mothers were screened for colonization with ESBL-E and MRSA. Demographic and clinical data were obtained from the German nationwide surveillance system for nosocomial infections in VLBW infants (NEO-KISS) and used to perform univariate and multivariate analyses. Of 209 VLBW infants, 12 (5.7%) were colonized with ESBL-E. Eighteen of 209 (8.6%) ESBL-E-tested neonates were related to an ESBL-E-positive mother. Univariate analysis, strain typing and multivariate analysis (OR 7.4, 95% CI 2.1-26.7, P = 0.002) identified an ESBL-E-positive mother and maternal-neonatal transmission as a main source of colonization. The prevalence of MRSA was 2.3% (5 of 221) among VLBW infants. One of the 221 (0.5%) MRSA-tested neonates was related to an MRSA-positive mother. No risk factors for transmission of MRSA could be detected in this study. Our study demonstrated that maternal-neonatal transmission of ESBL-E from mother to child is an important risk factor for colonization of VLBW infants. As a consequence, routine ESBL-E screening of neonates and mothers should be considered as a means of reducing neonatal morbidity and mortality. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Patients hospitalized abroad as importers of multiresistant bacteria-a cross-sectional study.

PubMed

Khawaja, T; Kirveskari, J; Johansson, S; Väisänen, J; Djupsjöbacka, A; Nevalainen, A; Kantele, A

2017-09-01

The pandemic spread of multidrug-resistant (MDR) bacteria poses a threat to healthcare worldwide, with highest prevalence in indigent regions of the (sub)tropics. As hospitalization constitutes a major risk factor for colonization, infection control management in low-prevalence countries urgently needs background data on patients hospitalized abroad. We collected data on 1122 patients who, after hospitalization abroad, were treated at the Helsinki University Hospital between 2010 and 2013. They were screened for methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), vancomycin-resistant enterococci, carbapenemase-producing Enterobacteriaceae (CPE), multiresistant Pseudomonas aeruginosa and multiresistant Acinetobacter baumannii. Risk factors for colonization were explored by multivariate analysis. MDR colonization rates were higher for those hospitalized in the (sub)tropics (55%; 208/377) compared with temperate zones (17%; 125/745). For ESBL-PE the percentages were 50% (190/377) versus 12% (92/745), CPE 3.2% (12/377) versus 0.4% (3/745) and MRSA 6.6% (25/377) versus 2.4% (18/745). Colonization rates proved highest in those returning from South Asia (77.6%; 38/49), followed by those having visited Latin America (60%; 9/16), Africa (60%; 15/25) and East and Southeast Asia (52.5%; 94/179). Destination, interhospital transfer, short time interval to hospitalization, young age, surgical intervention, residence abroad, visiting friends and relatives, and antimicrobial use proved independent risk factors for colonization. Post-hospitalization colonization rates proved higher in the (sub)tropics than elsewhere; 11% (38/333) of carriers developed an MDR infection. We identified several independent risk factors for contracting MDR bacteria. The data provide a basis for infection control guidelines in low-prevalence countries. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Lucky number seven: RNase 7 can prevent Staphylococcus aureus skin colonization.

PubMed

Cho, John S; Xuan, Caiyun; Miller, Lloyd S

2010-12-01

Staphylococcus aureus colonization is a major risk factor for infection. In this issue, Simanski et al. demonstrate that the antimicrobial peptide RNase 7 is essential for preventing S. aureus colonization in human skin. These findings suggest that therapeutic interventions aimed at targeting RNase 7 production in the skin may be a novel strategy to protect against S. aureus infections.

Predisposing factors for colonic torsion/volvulus in dogs: a retrospective study of six cases (1992-2010).

PubMed

Gagnon, Dominique; Brisson, Brigitte

2013-01-01

The purposes of this retrospective study were to review cases of colonic torsion/volvulus between July 1992 and August 2010 and to determine if any predisposing factors exist for the development of this condition. Six dogs were diagnosed with colonic torsion/volvulus during the study period. Four dogs had a history of previous gastric dilation-volvulus (GDV) with prophylactic gastropexy. Three of six dogs diagnosed with colonic torsion/volvulus had large intestinal entrapment and strangulation around the gastropexy site at the time of surgery. The history, clinical signs, physical examination, and radiologic findings were not specific for colonic torsion/volvulus in any dog. Early exploratory laparotomy was indicated to confirm the diagnosis and perform surgical correction of the affected bowel segments. Three of five dogs that underwent surgery had a left abdominal wall colopexy performed. All five dogs that underwent surgery in this study survived postoperatively. One patient was euthanized without surgical intervention. Results suggest that colonic torsion/volvulus should be considered in any large-breed dog with nonspecific gastrointestinal clinical signs and a history of previous gastropexy. Early recognition and prompt treatment of this condition may result in a good outcome.

Linking extinction-colonization dynamics to genetic structure in a salamander metapopulation.

PubMed

Cosentino, Bradley J; Phillips, Christopher A; Schooley, Robert L; Lowe, Winsor H; Douglas, Marlis R

2012-04-22

Theory predicts that founder effects have a primary role in determining metapopulation genetic structure. However, ecological factors that affect extinction-colonization dynamics may also create spatial variation in the strength of genetic drift and migration. We tested the hypothesis that ecological factors underlying extinction-colonization dynamics influenced the genetic structure of a tiger salamander (Ambystoma tigrinum) metapopulation. We used empirical data on metapopulation dynamics to make a priori predictions about the effects of population age and ecological factors on genetic diversity and divergence among 41 populations. Metapopulation dynamics of A. tigrinum depended on wetland area, connectivity and presence of predatory fish. We found that newly colonized populations were more genetically differentiated than established populations, suggesting that founder effects influenced genetic structure. However, ecological drivers of metapopulation dynamics were more important than age in predicting genetic structure. Consistent with demographic predictions from metapopulation theory, genetic diversity and divergence depended on wetland area and connectivity. Divergence was greatest in small, isolated wetlands where genetic diversity was low. Our results show that ecological factors underlying metapopulation dynamics can be key determinants of spatial genetic structure, and that habitat area and isolation may mediate the contributions of drift and migration to divergence and evolution in local populations.

Indications for and outcome of primary repair compared with faecal diversion in the management of traumatic colon injury.

PubMed

Fouda, E; Emile, S; Elfeki, H; Youssef, M; Ghanem, A; Fikry, A A; Elshobaky, A; Omar, W; Khafagy, W; Morshed, M

2016-08-01

Injuries of the colon are a serious sequel of abdominal trauma owing to the associated morbidity and mortality. This study aims to assess postoperative outcome and complications of faecal diversion and primary repair of colon injuries when applied according to established guidelines for the management of colon injuries. This retrospective study was conducted on 110 patients with colon injuries. Guided by estimation of risk factors, patients were managed either by primary repair alone, repair with proximal diversion or diversion alone. There were 102 (92.7%) male patients and 8 (7.3%) female patients of median age 38 years. Thirty-seven were managed by primary repair and 73 by faecal diversion. Colon injuries were caused by penetrating abdominal trauma in 65 and blunt trauma in 45 patients. Forty-three patients were in shock on admission, and were all managed by faecal diversion. Forty patients developed 84 complications after surgery. Primary repair had a significantly lower complication rate than faecal diversion (P = 0.037). Wound infection was the commonest complication. The overall mortality rate was 3.6%. Primary repair, when employed properly, resulted in a significantly lower complication rate than faecal diversion. Significant predictive factors associated with a higher complication rate were faecal diversion, severe faecal contamination, multiple colon injuries, an interval of more than 12 h after colon injury and shock. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Candidal colonization, strain diversity, and antifungal susceptibility among adult diabetic patients.

PubMed

Al-Attas, Safia A; Amro, Soliman O

2010-01-01

Candidal colonization in diabetics is a matter of debate. The aim of this study is to investigate oral candidal colonization, strain diversity, antifungal susceptibility, and the influence of local and systemic host factors on candidal colonization in adult diabetics. We conducted a case-control study that compared 150 diabetics (49 type 1, 101 type 2) with 50 healthy controls. Two salivary samples were collected, using the oral rinse sampling method: one for salivary flow rate and pH determination, and the other for candidal colonization assessment. The candidal isolates were identified and tested in vitro for antifungal susceptibility using the commercial kit, Candifast. The relationship between specific host factors and candidal colonization was also investigated. Diabetics had a higher candidal carriage rate compared to controls, but not density. Candida albicans was the most frequently isolated species, but diabetics had a variety of other candidal species present. None of the control samples were resistant to any tested antifungal, while the diabetic samples had differing resistances to azole antifungals. Although there was a significant positive correlation between glycemic control and candidal colonization in type 2 diabetics, there was a negative correlation between salivary pH and candidal carriage in the controls versus density in type 2 diabetics. Diabetic patients not only had a higher candidal carriage rate, but also a variety of candidal species that were resistant to azole antifungals. Oral candidal colonization was significantly associated with glycemic control, type of diabetes, and salivary pH.

Association of healthcare exposure with acquisition of different Clostridium difficile strain types in patients with recurrent infection or colonization after clinical resolution of initial infection.

PubMed

Thabit, A K; Housman, S T; Burnham, C D; Nicolau, D P

2016-02-01

Following the resolution of an episode of Clostridium difficile infection (CDI), the factors associated with acquisition of different C. difficile strain types in patients with recurrent infection or persistent colonization have not been evaluated. To explore factors with potential correlation with acquisition of different C. difficile strain types in patients clinically cured of CDI through long-term follow-up across the continuum of care. Polymerase chain reaction ribotyping was performed on C. difficile isolates recovered at baseline and follow-up (days 19-38) from stool samples of patients successfully treated for CDI, and those who had recurrence and/or colonization following symptom resolution. Chart review was conducted to determine factors associated with acquisition of a different C. difficile ribotype. Of 25 patients initially cured of CDI, five had a recurrence and eight were colonized at follow-up. Patients did not differ with regard to age, sex, and whether the initial infection was with the BI/NAP1/027 strain. Ribotyping revealed that two out of five patients had recurrence attributed to a different strain type. Three of the colonized patients demonstrated strain switching compared with five patients who carried the same baseline strain. All patients (both infected and colonized) with different C. difficile ribotypes were exposed to the healthcare system. Exposure to antibiotics and proton pump inhibitors were not related to strain switching. Exposure to healthcare, but not to antibiotics or proton pump inhibitors, was consistently associated with recurrence or colonization with a different C. difficile ribotype. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Meta-analysis of racial disparities in survival in association with socioeconomic status among men and women with colon cancer.

PubMed

Du, Xianglin L; Meyer, Tamra E; Franzini, Luisa

2007-06-01

Few studies have addressed racial disparities in survival for colon cancer by adequately incorporating both treatment and socioeconomic factors, and the findings from those studies have been inconsistent. The objectives of the current study were to systematically review the existing literature and provide a more stable estimate of the measures of association between socioeconomic status and racial disparities in survival for colon cancer by undertaking a meta-analysis. For this meta-analysis, the authors searched the MEDLINE database to identify articles published in English from 1966 to August 2006 that met the following inclusion criteria: original research articles that addressed the association between race/ethnicity and survival in patients with colon or colorectal cancer after adjusting for socioeconomic status. In total, 66 full articles were reviewed, and 56 of those articles were excluded, which left 10 studies for the final analysis. The pooled hazard ratio (HR) for African Americans compared with Caucasians was 1.14 (95% confidence interval [95% CI], 1.00-1.29) for all-cause mortality and 1.13 (95% CI, 1.01-1.28) for colon cancer-specific mortality. The test for homogeneity of the HR was statistically significant across the studies for all-cause mortality (Q=31.69; P<.001) but was not significant across the studies for colon cancer-specific mortality (Q=7.45; P=.114). Racial disparities in survival for colon cancer between African Americans and Caucasians were only marginally significant after adjusting for socioeconomic factors and treatment. Attempts to modify treatment and socioeconomic factors with the objective of reducing racial disparities in health outcomes may have important clinical and public health implications. (c) 2007 American Cancer Society.

RegA, an AraC-like protein, is a global transcriptional regulator that controls virulence gene expression in Citrobacter rodentium.

PubMed

Hart, Emily; Yang, Ji; Tauschek, Marija; Kelly, Michelle; Wakefield, Matthew J; Frankel, Gad; Hartland, Elizabeth L; Robins-Browne, Roy M

2008-11-01

Citrobacter rodentium is an attaching and effacing pathogen which causes transmissible colonic hyperplasia in mice. Infection with C. rodentium serves as a model for infection of humans with enteropathogenic and enterohemorrhagic Escherichia coli. To identify novel colonization factors of C. rodentium, we screened a signature-tagged mutant library of C. rodentium in mice. One noncolonizing mutant had a single transposon insertion in an open reading frame (ORF) which we designated regA because of its homology to genes encoding members of the AraC family of transcriptional regulators. Deletion of regA in C. rodentium resulted in markedly reduced colonization of the mouse intestine. Examination of lacZ transcriptional fusions using promoter regions of known and putative virulence-associated genes of C. rodentium revealed that RegA strongly stimulated transcription of two newly identified genes located close to regA, which we designated adcA and kfcC. The cloned adcA gene conferred autoaggregation and adherence to mammalian cells to E. coli strain DH5alpha, and a kfc mutation led to a reduction in the duration of intestinal colonization, but the kfc mutant was far less attenuated than the regA mutant. These results indicated that other genes of C. rodentium whose expression required activation by RegA were required for colonization. Microarray analysis revealed a number of RegA-regulated ORFs encoding proteins homologous to known colonization factors. Transcription of these putative virulence determinants was activated by RegA only in the presence of sodium bicarbonate. Taken together, these results show that RegA is a global regulator of virulence in C. rodentium which activates factors that are required for intestinal colonization.

RegA, an AraC-Like Protein, Is a Global Transcriptional Regulator That Controls Virulence Gene Expression in Citrobacter rodentium▿

PubMed Central

Hart, Emily; Yang, Ji; Tauschek, Marija; Kelly, Michelle; Wakefield, Matthew J.; Frankel, Gad; Hartland, Elizabeth L.; Robins-Browne, Roy M.

2008-01-01

Citrobacter rodentium is an attaching and effacing pathogen which causes transmissible colonic hyperplasia in mice. Infection with C. rodentium serves as a model for infection of humans with enteropathogenic and enterohemorrhagic Escherichia coli. To identify novel colonization factors of C. rodentium, we screened a signature-tagged mutant library of C. rodentium in mice. One noncolonizing mutant had a single transposon insertion in an open reading frame (ORF) which we designated regA because of its homology to genes encoding members of the AraC family of transcriptional regulators. Deletion of regA in C. rodentium resulted in markedly reduced colonization of the mouse intestine. Examination of lacZ transcriptional fusions using promoter regions of known and putative virulence-associated genes of C. rodentium revealed that RegA strongly stimulated transcription of two newly identified genes located close to regA, which we designated adcA and kfcC. The cloned adcA gene conferred autoaggregation and adherence to mammalian cells to E. coli strain DH5α, and a kfc mutation led to a reduction in the duration of intestinal colonization, but the kfc mutant was far less attenuated than the regA mutant. These results indicated that other genes of C. rodentium whose expression required activation by RegA were required for colonization. Microarray analysis revealed a number of RegA-regulated ORFs encoding proteins homologous to known colonization factors. Transcription of these putative virulence determinants was activated by RegA only in the presence of sodium bicarbonate. Taken together, these results show that RegA is a global regulator of virulence in C. rodentium which activates factors that are required for intestinal colonization. PMID:18765720

Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: Implications for obesity-associated colon carcinogenesis.

PubMed

Song, Na-Young; Lee, Yeon-Hwa; Na, Hye-Kyung; Baek, Jeong-Heum; Surh, Young-Joon

2018-07-01

Leptin, a representative adipokine secreted from the white adipose tissue, is considered as a potential linker between obesity and cancer. SIRT1 is an NAD + -dependent histone/protein deacetylase speculated to function as an oncogene. In the present study, we found that leptin signaling-defective ob/ob and db/db mice had lower colonic expression of SIRT1 compared with leptin signaling-intact C57BL/6J mice, implying that leptin signaling is crucial for SIRT1 expression in vivo. Moreover, leptin induced up-regulation of SIRT1 in human colon cancer (HCT-116) cells. Leptin stimulated migration and invasion of cultured HCT-116 cells and tumor growth in the xenograft assay, and these effects were abrogated by a SIRT1 inhibitor sirtinol, suggesting that SIRT1 plays a role in leptin-induced colon carcinogenesis. Leptin-induced SIRT1 expression was regulated by the redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2). Leptin stimulated nuclear accumulation of Nrf2 as well as its binding to the antioxidant response elements located in the SIRT1 promoter. Moreover, siRNA knockdown of Nrf2 abrogated the leptin-induced SIRT1 expression. Notably, SIRT1 was significantly reduced in colon tissues of Nrf2-null mice, lending further support to Nrf2-dependent SIRT1 expression. Expression of leptin, Nrf2 and SIRT1 was coordinately increased in human colon tumor tissues. In conclusion, leptin might play a role in colon carcinogenesis by inducing Nrf2-dependent SIRT1 overexpression. Copyright © 2018 Elsevier Inc. All rights reserved.

[Risk factors for Pseudomonas aeruginosa infections, resistant to carbapenem].

PubMed

Ghibu, Laura; Miftode, Egidia; Teodor, Andra; Bejan, Codrina; Dorobăţ, Carmen Mihaela

2010-01-01

Since their introduction in clinical practice,carbapenems have been among the most powerful antibiotics for treating serious infections cased by Gram-negative nosocomial pathogens, including Pseudomonas aeruginosa. The emergence of betalactamases with carbapenem-hydrolyzing activity is of major clinical concern. Pseudomonas aeruginosa is a leading cause of nosocomial infection. Risk factors for colonization with carbapenems-resistant Pseudomonas in hospital are: history of P. aeruginosa infection or colonization within the previous year, (length of hospital stay, being bedridden or in the ICU, mechanical ventilation, malignant disease, and history of chronic obstructive pulmonary disease have all been identified as independent risk factors for MDR P. aeruginosa infection. Long-term-care facilities are also reservoirs of resistant bacteria. Risk factors for colonization of LTCF residents with resistant bacteria included age > 86 years, antibiotic treatment in the previous 3 months, indwelling devices, chronic obstructive pulmonary disease, physical disability, and the particular LTCF unit.

Risk factors for colonization and infection by Pseudomonas aeruginosa in patients hospitalized in intensive care units in France

PubMed Central

Hoang, S.; Georget, A.; Asselineau, J.; Venier, A-G.; Leroyer, C.; Rogues, A. M.; Thiébaut, R.

2018-01-01

Pseudomonas aeruginosa (P.aeruginosa) remains a prominent nosocomial pathogen responsible for high morbi-mortality in intensive care units (ICUs). P.aeruginosa transmission is known to be partly endogenous and exogenous. Main factors have been highlighted but the precise role of environment in regard to antibiotics use remained unclear. Objective To assess the role of environment, medical care and individual risks factors for P. aeruginosa colonization and infection. Study design and setting A French multicentric prospective study involved ten ICUs for a five months period. Every adult patient newly hospitalized in ICUs with no P. aeruginosa carriage up to 48 hours after admission was included and weekly screened before discharge or death. Screening swabs were either rectal, sputum or oropharyngeal samples. Hydric environment was also sampled each week. Data on patient clinical features, environmental and device exposures, and antibiotics supports were regularly collected. Multivariate analysis was performed with a multistate model. Results The overall prevalence of P. aeruginosa carriage was 15.3% (201/1314). Risk factors associated with patient colonization were: use of inactive antibiotics against P. aeruginosa (HR = 1.60 [1.15–2.21] p<0.01), tap water contamination at the entry in the room (HR = 1.66 [1.01–2.27] p<0.05) and mechanical invasive ventilation (HR = 4.70 [2.66–8.31] p<0.0001). Active antibiotics prevented from colonization (HR = 0.67 [0.48–0.93] p = 0.02) and from infection (HR = 0.64 [0.41–1.01] p = 0.05). Interaction between hydric environment antibiotics support was not statistically associated with patient colonization. Conclusion Hydric contamination and antibiotics pressure seem to remain key independent risk factors in P. aeruginosa colonization. These results advocate the need to carry on preventive and targeted interventions toward healthcare associated infections. PMID:29522559

Oxidative balance and colon and rectal cancer: interaction of lifestyle factors and genes.

PubMed

Slattery, Martha L; Lundgreen, Abbie; Welbourn, Bill; Wolff, Roger K; Corcoran, Christopher

2012-06-01

Pro-oxidant and anti-oxidant genetic and lifestyle factors can contribute to an individual's level of oxidative stress. We hypothesize that diet, lifestyle and genetic factors work together to influence colon and rectal cancer through an oxidative balance mechanism. We evaluated nine markers for eosinophil peroxidase (EPX), two for myeloperoxidase (MPO), four for hypoxia-inducible factor-1A (HIFIA), and 16 for inducible nitric oxide synthase (NOS2A) in conjunction with dietary antioxidants, aspirin/NSAID use, and cigarette smoking. We used data from population-based case-control studies (colon cancer n=1555 cases, 1956 controls; rectal cancer n=754 cases, 959 controls). Only NOS2A rs2297518 was associated with colon cancer (OR 0.86 95% CI 0.74, 0.99) and EPX rs2302313 and MPO rs2243828 were associated with rectal cancer (OR 0.75 95% CI 0.59, 0.96; OR 0.81 95% CI 0.67, 0.99 respectively) for main effects. However, after adjustment for multiple comparisons we observed the following significant interactions for colon cancer: NOS2A and lutein, EPX and aspirin/NSAID use, and NOS2A (4 SNPs) and cigarette smoking. For rectal cancer we observed the following interactions after adjustment for multiple comparisons: HIF1A and vitamin E, NOS2A (3SNPs) with calcium; MPO with lutein; HIF1A with lycopene; NOS2A with selenium; EPX and NOS2A with aspirin/NSAID use; HIF1A, MPO, and NOS2A (3 SNPs) with cigarette smoking. We observed significant interaction between a composite oxidative balance score and a polygenic model for both colon (p interaction 0.0008) and rectal cancer (p=0.0018). These results suggest the need to comprehensively evaluate interactions to assess the contribution of risk from both environmental and genetic factors. Copyright © 2012 Elsevier B.V. All rights reserved.

Transcriptional regulation of defence genes and involvement of the WRKY transcription factor in arbuscular mycorrhizal potato root colonization.

PubMed

Gallou, Adrien; Declerck, Stéphane; Cranenbrouck, Sylvie

2012-03-01

The establishment of arbuscular mycorrhizal associations causes major changes in plant roots and affects significantly the host in term of plant nutrition and resistance against biotic and abiotic stresses. As a consequence, major changes in root transcriptome, especially in plant genes related to biotic stresses, are expected. Potato microarray analysis, followed by real-time quantitative PCR, was performed to detect the wide transcriptome changes induced during the pre-, early and late stages of potato root colonization by Glomus sp. MUCL 41833. The microarray analysis revealed 526 up-regulated and 132 down-regulated genes during the pre-stage, 272 up-regulated and 109 down-regulated genes during the early stage and 734 up-regulated and 122 down-regulated genes during the late stage of root colonization. The most important class of regulated genes was associated to plant stress and in particular to the WRKY transcription factors genes during the pre-stage of root colonization. The expression profiling clearly demonstrated a wide transcriptional change during the pre-, early and late stages of root colonization. It further suggested that the WRKY transcription factor genes are involved in the mechanisms controlling the arbuscular mycorrhizal establishment by the regulation of plant defence genes.

An outbreak of vancomycin-resistant Enterococcus faecium in an acute care pediatric hospital: Lessons from environmental screening and a case-control study

PubMed Central

Drews, Steven J; Richardson, Susan E; Wray, Rick; Freeman, Renee; Goldman, Carol; Streitenberger, Laurie; Stevens, Derek; Goia, Cristina; Kovach, Danuta; Brophy, Jason; Matlow, Anne G

2008-01-01

BACKGROUND The present study describes a vancomycin-resistant enterococci (VRE) outbreak investigation and a case-control study to identify risk factors for VRE acquisition in a tertiary care pediatric hospital. OBJECTIVE To report an outbreak investigation and a case-control study to identify risk factors for VRE colonization or infection in hospitalized children. METHODS Screening for VRE cases was performed by culture or polymerase chain reaction. A case-control study of VRE-colonized patients was undertaken. Environmental screening was performed using standard culture and susceptibility methods, with pulsed-field gel electrophoresis to determine relationships between VRE isolates. Statistical analysis was performed using SAS version 9.0 (SAS Institute Inc, USA). RESULTS Thirty-four VRE-positive cases were identified on 10 wards between February 28, 2005, and May 27, 2005. Pulsed-field gel electrophoresis analysis confirmed a single outbreak strain that was also isolated from a video game found on one affected ward. Multivariate analysis identified cephalosporin use as the major risk factor for VRE colonization. CONCLUSIONS In the present study outbreak, VRE colonization was significantly associated with cephalosporin use. Because shared recreational items and environmental surfaces may be colonized by VRE, they warrant particular attention in housekeeping protocols, particularly in pediatric institutions. PMID:19412380

Risk Factors for Colonization of E. coli in Atlantic Bottlenose Dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida

PubMed Central

Schaefer, Adam M.; Bossart, Gregory D.; Mazzoil, Marilyn; Fair, Patricia A.; Reif, John S.

2011-01-01

Opportunistic pathogens related to degradation in water quality are of concern to both wildlife and public health. The objective of this study was to identify spatial, temporal, and environmental risk factors for E. coli colonization among Atlantic bottlenose dolphins (Tursiops truncatus) inhabiting the Indian River Lagoon (IRL), FL between 2003 and 2007. Age, gender, capture location, coastal human population density, proximity of sewage treatment plants, number of septic tanks, cumulative precipitation 48 hrs and 30 days prior to capture, salinity, and water temperature were analyzed as potential risk factors. Highest E. coli colonization rates occurred in the northern segments of the IRL. The risk of E. coli colonization was the highest among the youngest individuals, in counties with the highest cumulative rainfall 48 hrs and in counties with the highest number of septic systems during the year of capture. The prevalence of colonization was the highest during 2004, a year during which multiple hurricanes hit the coast of Florida. Septic tanks, in combination with weather-related events suggest a possible pathway for introduction of fecal coliforms into estuarine ecosystems. The ability of E. coli and related bacteria to act as primary pathogens or cause opportunistic infections adds importance of these findings. PMID:21977048

Risk factors for colonization of E. coli in Atlantic Bottlenose Dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida.

PubMed

Schaefer, Adam M; Bossart, Gregory D; Mazzoil, Marilyn; Fair, Patricia A; Reif, John S

2011-01-01

Opportunistic pathogens related to degradation in water quality are of concern to both wildlife and public health. The objective of this study was to identify spatial, temporal, and environmental risk factors for E. coli colonization among Atlantic bottlenose dolphins (Tursiops truncatus) inhabiting the Indian River Lagoon (IRL), FL between 2003 and 2007. Age, gender, capture location, coastal human population density, proximity of sewage treatment plants, number of septic tanks, cumulative precipitation 48 hrs and 30 days prior to capture, salinity, and water temperature were analyzed as potential risk factors. Highest E. coli colonization rates occurred in the northern segments of the IRL. The risk of E. coli colonization was the highest among the youngest individuals, in counties with the highest cumulative rainfall 48 hrs and in counties with the highest number of septic systems during the year of capture. The prevalence of colonization was the highest during 2004, a year during which multiple hurricanes hit the coast of Florida. Septic tanks, in combination with weather-related events suggest a possible pathway for introduction of fecal coliforms into estuarine ecosystems. The ability of E. coli and related bacteria to act as primary pathogens or cause opportunistic infections adds importance of these findings.

Pro-apoptotic activities of polyphenolics from açai (Euterpe oleracea Martius) in human SW-480 colon cancer cells.

PubMed

Dias, Manoela Maciel dos Santos; Noratto, Giuliana; Martino, Hercia Stampini Duarte; Arbizu, Shirley; Peluzio, Maria do Carmo Gouveia; Talcott, Stephen; Ramos, Afonso Mota; Mertens-Talcott, Susanne U

2014-01-01

This study aimed to evaluate the cell growth inhibition activity of açai (Euterpe oleracea Mart.) polyphenolic extract against colon cancer HT-29 and SW-480 cells and the nonmalignant CCD-18Co colon fibroblast cells. Results showed that açai polyphenolic extract (5-20 mg/L) inhibited preferentially the growth of SW-480 cells with no toxicity in CCD-18Co cells, and this was accompanied by reduction of H2O2-induced reactive oxygen species (ROS) generation. The mechanisms involved in SW-480 cell growth-inhibition by açai polyphenolic extract included the downregulation of NF-κB proinflammatory transcription factor and the nuclear factor-kappa B targets intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, prooncogenic specificity proteins (Sp) were downregulated as well as Sp-targets Bcl-2, vascular endothelial growth factor, and survivin. This was accompanied by activation of mitochondrial proapoptotic pathway involving increase of cytochrome c, cleavage of caspase-3, and decrease of PARP-1. Results strongly suggest that açai polyphenolic extract has antiinflammatory and cytotoxic activities in colon cancer cells and can be effective as natural colon cancer chemopreventive agents.

Pneumoperitoneum after virtual colonoscopy: causes, risk factors, and management.

PubMed

Baccaro, Leopoldo M; Markelov, Alexey; Wilhelm, Jakub; Bloch, Robert

2014-06-01

Computed tomographic virtual colonoscopy (CTVC) is a safe and minimally invasive modality when compared with fiberoptic colonoscopy for evaluating the colon and rectum. We have reviewed the risks for colonic perforation by investigating the relevant literature. The objectives of this study were to assess the risk of colonic perforation during CTVC, describe risk factors, evaluate ways to reduce the incidence complications, and to review management and treatment options. A formal search of indexed publications was performed through PubMed. Search queries using keywords "CT colonography," "CT virtual colonoscopy," "virtual colonoscopy," and "perforation" yielded a total of 133 articles. A total of eight case reports and four review articles were selected. Combining case reports and review articles, a total of 25 cases of colonic perforation after CTVC have been reported. Causes include, but are not limited to, diverticular disease, irritable bowel diseases, obstructive processes, malignancies, and iatrogenic injury. Both operative and nonoperative management has been described. Nonoperative management has been proven safe and successful in minimally symptomatic and stable patients. Colonic perforation after CTVC is a rare complication and very few cases have been reported. Several risk factors are recurrent in the literature and must be acknowledged at the time of the study. Management options vary and should be tailored to each individual patient.

Battery Electric Vehicle Driving and Charging Behavior Observed Early in The EV Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

John Smart; Stephen Schey

2012-04-01

As concern about society's dependence on petroleum-based transportation fuels increases, many see plug-in electric vehicles (PEV) as enablers to diversifying transportation energy sources. These vehicles, which include plug-in hybrid electric vehicles (PHEV), range-extended electric vehicles (EREV), and battery electric vehicles (BEV), draw some or all of their power from electricity stored in batteries, which are charged by the electric grid. In order for PEVs to be accepted by the mass market, electric charging infrastructure must also be deployed. Charging infrastructure must be safe, convenient, and financially sustainable. Additionally, electric utilities must be able to manage PEV charging demand on themore » electric grid. In the Fall of 2009, a large scale PEV infrastructure demonstration was launched to deploy an unprecedented number of PEVs and charging infrastructure. This demonstration, called The EV Project, is led by Electric Transportation Engineering Corporation (eTec) and funded by the U.S. Department of Energy. eTec is partnering with Nissan North America to deploy up to 4,700 Nissan Leaf BEVs and 11,210 charging units in five market areas in Arizona, California, Oregon, Tennessee, and Washington. With the assistance of the Idaho National Laboratory, eTec will collect and analyze data to characterize vehicle consumer driving and charging behavior, evaluate the effectiveness of charging infrastructure, and understand the impact of PEV charging on the electric grid. Trials of various revenue systems for commercial and public charging infrastructure will also be conducted. The ultimate goal of The EV Project is to capture lessons learned to enable the mass deployment of PEVs. This paper is the first in a series of papers documenting the progress and findings of The EV Project. This paper describes key research objectives of The EV Project and establishes the project background, including lessons learned from previous infrastructure deployment and PEV demonstrations. One such previous study was a PHEV demonstration conducted by the U.S. Department of Energy's Advanced Vehicle Testing Activity (AVTA), led by the Idaho National Laboratory (INL). AVTA's PHEV demonstration involved over 250 vehicles in the United States, Canada, and Finland. This paper summarizes driving and charging behavior observed in that demonstration, including the distribution of distance driven between charging events, charging frequency, and resulting proportion of operation charge depleting mode. Charging demand relative to time of day and day of the week will also be shown. Conclusions from the PHEV demonstration will be given which highlight the need for expanded analysis in The EV Project. For example, the AVTA PHEV demonstration showed that in the absence of controlled charging by the vehicle owner or electric utility, the majority of vehicles were charged in the evening hours, coincident with typical utility peak demand. Given this baseline, The EV Project will demonstrate the effects of consumer charge control and grid-side charge management on electricity demand. This paper will outline further analyses which will be performed by eTec and INL to documenting driving and charging behavior of vehicles operated in a infrastructure-rich environment.« less

Risk factors associated with the community-acquired colonization of extended-spectrum beta-lactamase (ESBL) positive Escherichia Coli. an exploratory case-control study.

PubMed

Leistner, Rasmus; Meyer, Elisabeth; Gastmeier, Petra; Pfeifer, Yvonne; Eller, Christoph; Dem, Petra; Schwab, Frank

2013-01-01

The number of extended-spectrum beta-lactamase (ESBL) positive (+) Escherichia coli is increasing worldwide. In contrast with many other multidrug-resistant bacteria, it is suspected that they predominantly spread within the community. The objective of this study was to assess factors associated with community-acquired colonization of ESBL (+) E. coli. We performed a matched case-control study at the Charité University Hospital Berlin between May 2011 and January 2012. Cases were defined as patients colonized with community-acquired ESBL (+) E. coli identified <72 h after hospital admission. Controls were patients that carried no ESBL-positive bacteria but an ESBL-negative E.coli identified <72 h after hospital admission. Two controls per case were chosen from potential controls according to admission date. Case and control patients completed a questionnaire assessing nutritional habits, travel habits, household situation and language most commonly spoken at home (mother tongue). An additional rectal swab was obtained together with the questionnaire to verify colonization status. Genotypes of ESBL (+) E. coli strains were determined by PCR and sequencing. Risk factors associated with ESBL (+) E. coli colonization were analyzed by a multivariable conditional logistic regression analysis. We analyzed 85 cases and 170 controls, respectively. In the multivariable analysis, speaking an Asian language most commonly at home (OR = 13.4, CI 95% 3.3-53.8; p<0.001) and frequently eating pork (≥ 3 meals per week) showed to be independently associated with ESBL colonization (OR = 3.5, CI 95% 1.8-6.6; p<0.001). The most common ESBL genotypes were CTX-M-1 with 44% (n = 37), CTX-M-15 with 28% (n = 24) and CTX-M-14 with 13% (n = 11). An Asian mother tongue and frequently consuming certain types of meat like pork can be independently associated with the colonization of ESBL-positive bacteria. We found neither frequent consumption of poultry nor previous use of antibiotics to be associated with ESBL colonization.

A ten-year study of penetrating injuries of the colon.

PubMed

Adesanya, Adedoyin A; Ekanem, Ekanem E

2004-12-01

Colon injury has been associated with a high risk of septic complications and mortality. We prospectively studied the pattern, management, outcome, and prognostic factors in patients who sustained penetrating colon injuries. Sixty patients who presented to our hospital with penetrating colon injuries over a ten-year period (1992 to 2001) were studied. Colon wounds were caused by gunshots in 55 (91.7 percent) patients and knife stabs in 5 (8.3 percent). There was a delay of more than 12 hours before laparotomy in 30 (50 percent) patients. Moderate or major fecal contamination of the peritoneal cavity occurred in 58 (96.7 percent) patients. The average penetrating abdominal trauma index score was 25.9 and 20 (33.3 percent) patients sustained Flint Grade 3 colon injury. Associated intra-abdominal injuries occurred in the small bowel (73.3 percent), liver (25 percent), stomach (23.3 percent), and mesentery (16.7 percent). Right colon wounds (35) were managed by primary repair in 24 (68.6 percent) patients and proximal diverting colostomy in 11 (31.4 percent), whereas left colon wounds (25) were managed by diverting colostomy in 22 (88.0 percent) patients and primary repair in 3 (12.0 percent) patients. Common complications included wound infection (56.7 percent), septicemia (31.7 percent), and enterocutaneous fistula (16.7 percent). The overall mortality rate was 33.3 percent and colon injury-related mortality was 21.7 percent. Presence of destructive colon injury was associated with a greater than fourfold increased incidence of death. Other significant risk factors included shock on admission, major fecal contamination, duration of operation more than four hours, penetrating abdominal trauma index score >25, and more than two postoperative complications. There was no difference in outcome between patients who had primary repair and those undergoing diverting colostomy. Colostomy closure-related morbidity was 21 percent and mortality was 5.3 percent. A more liberal use of primary repair is required in our patients with penetrating injuries of the colon.

Effects of modified Sanhuang decoction () enema on serum tumor necrosis factor-α and colonic mucosa interleukin-1β, interleukin-6 levels in ulcerative colitis rats.

PubMed

Wang, Shuai; Zhou, Tao; Zhai, Jun-Peng; Wang, Li-Hua; Chen, Jing

2014-11-01

To investigate the effects of Modified Sanhuang Decoction (, MSD) enema on the serum tumor necrosis factor alpha (TNF-α) and colonic mucosa interleukin-1β (IL-1β), interleukin-6 (IL-6) levels in experimental ulcerative colitis (UC) rats. Forty-five male Wistar rats were randomly divided into 4 groups: normal group (n=12), model group (n=11), salazosulfapyridine (SASP) group (n=11) and MSD group (n=11). The UC model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Rats in the normal group and model group were clystered with 0.9% normal saline, while in the SASP group and MSD group were clystered with SASP and MSD enema, respectively. After drug administration (10 mL/kg body weight, for 7 days), colonic gross changes and colonic mucosa histology were observed, serum TNF-α and colonic mucosa IL-1β, IL-6 levels were tested by enzyme linked immunosorbent assay and radioimmunoassay, respectively. As compared with the normal group, the experimental UC rats, the colonic mucosal damage index scores (CMDIs), histopathological scores (HS) and the serum TNF-α and colonic mucosa IL-1β, IL-6 levels significantly increased (P<0.05 or P<0.01). In the MSD and SASP groups, the ulcer area significantly reduced, and edema disappeared. The CMDIs, HS, the serum TNF-α and colonic mucosa IL-1β, IL-6 levels in the MSD and SASP groups significantly decreased (P<0.05 or P<0.01) compared with the model group. The CMDIs in the MSD group were lower than that in the SASP group (P<0.05), but there were no significant differences in HS, serum TNF-α or colonic mucosa IL-1β, IL-6 levels between the MSD and SASP groups. MSD enema can improve colonic mucosa impairment and decrease serum TNF-α and colonic mucosa IL-1β, IL-6 levels in experimental UC.

Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Zehua; Cui, Feifei; Yu, Fudong

2014-06-27

Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) wasmore » significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.« less

Aging and chronic alcohol consumption are determinants of p16 gene expression, genomic DNA methylation and p16 promoter methylation in the mouse colon

USDA-ARS?s Scientific Manuscript database

Elder age and chronic alcohol consumption are important risk factors for the development of colon cancer. Each factor can alter genomic and gene-specific DNA methylation. This study examined the effects of aging and chronic alcohol consumption on genomic and p16-specific methylation, and p16 express...

Ageing, chronic alcohol consumption and folate are determinants of genomic DNA methylation, p16 promoter methylation and the expression of p16 in the mouse colon

USDA-ARS?s Scientific Manuscript database

Elder age and chronic alcohol consumption are important risk factors for the development of colon cancer. Each factor can alter genomic and gene-specific DNA methylation. This study examined the effects of aging and chronic alcohol consumption on genomic and p16-specific methylation, and p16 express...

Pathophysiology of diverticular disease.

PubMed

Schieffer, Kathleen M; Kline, Bryan P; Yochum, Gregory S; Koltun, Walter A

2018-06-07

Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

Evaluation of prevalence and risk factors for methicillin-resistant Staphylococcus aureus colonization in veterinary personnel attending an international equine veterinary conference.

PubMed

Anderson, Maureen E C; Lefebvre, Sandra L; Weese, J Scott

2008-06-22

Infection and colonization with methicillin-resistant Staphylococcus aureus (MRSA) are now increasingly being reported in animals and people who work with animals, including horses and horse personnel. The objectives of this study were to evaluate the prevalence of MRSA colonization in veterinary personnel attending an international equine veterinary conference, and to identify risk factors for MRSA colonization in this group. Volunteers were recruited at the conference to provide a single nasal swab and complete a questionnaire regarding contact with the human health care system, contact with horses, and personal hand hygiene. Colonization with MRSA was found in 26/257 (10.1%) of study participants. Multivariable analysis showed an increased risk of MRSA colonization associated with having been diagnosed with or having treated a patient diagnosed with MRSA colonization or infection in the last year (odds ratio [OR] 8.41, 95% confidence interval [CI] 1.51-49.92, P=0.015; OR 3.27, 95% CI 1.05-10.11, P=0.039, respectively), whereas hand washing between infectious cases (OR 0.27, 95% CI 0.11-0.72, P=0.009) and hand washing between farms (OR 0.35, 95% CI 0.14-0.98, P=0.047) were protective. The prevalence of MRSA colonization among equine veterinary personnel found in this study was high compared to that of other studies of the general population. These data support previous suggestions that equine veterinary personnel are at increased risk of colonization with MRSA. This is the first study to demonstrate a statistically significant association between hand hygiene practices and a measurable clinical outcome in veterinary medicine.

Brain-Derived Neurotrophic Factor Contributes to Colonic Hypermotility in a Chronic Stress Rat Model.

PubMed

Quan, Xiaojing; Luo, Hesheng; Fan, Han; Tang, Qincai; Chen, Wei; Cui, Ning; Yu, Guang; Xia, Hong

2015-08-01

Brain-derived neurotrophic factor (BDNF) has prokinetic effects on gut motility and is increased in the colonic mucosa of irritable bowel syndrome. We aimed to investigate the possible involvement of BDNF in stress-induced colonic hypermotility. Male Wistar rats were exposed to daily 1-h water avoidance stress (WAS) or sham WAS for 10 consecutive days. The presence of BDNF and substance P (SP) in the colonic mucosa was determined using enzyme immunoassay kits. Immunohistochemistry and western blotting were performed to assess the expression of BDNF and its receptor, TrkB. The contractions of muscle strips were studied in an organ bath system. Repeated WAS increased the fecal pellet expulsion and spontaneous contractile activities of the colonic muscle strips. Both BDNF and SP in the colonic mucosa were elevated following WAS. Immunohistochemistry revealed the presence of BDNF and TrkB in the mucosa and myenteric plexus. BDNF and TrkB were both up-regulated in colon devoid of mucosa and submucosa from the stressed rats compared with the control. BDNF pretreatment caused an enhancement of the SP-induced contraction of the circular muscle (CM) strips. TrkB antibody significantly inhibited the contraction of the colonic muscle strips and attenuated the excitatory effects of SP on contractions of the CM strips. Repeated WAS increased the contractile activities of the CM strips induced by SP after BDNF pretreatment, and this effect was reversed by TrkB antibody. The colonic hypermotility induced by repeated WAS may be associated with the increased expression of endogenous BDNF and TrkB. BDNF may have potential clinical therapeutic use in modulating gut motility.

High prevalence of Staphylococcus aureus and methicillin-resistant S. aureus colonization among healthy children attending public daycare centers in informal settlements in a large urban center in Brazil.

PubMed

Braga, Eneida Dias Vianna; Aguiar-Alves, Fábio; de Freitas, Maria de Fátima Nogueira; de e Silva, Monique Oliveira; Correa, Thami Valadares; Snyder, Robert E; de Araújo, Verônica Afonso; Marlow, Mariel Asbury; Riley, Lee W; Setúbal, Sérgio; Silva, Licínio Esmeraldo; Araújo Cardoso, Claudete Aparecida

2014-10-06

In the past decade methicillin-resistant Staphylococcus aureus (MRSA) has become increasingly prevalent in community settings. Attending a daycare center (DCC) is a known risk factor for colonization with MRSA. Brazil operates free, public DCCs for low-income families, some of which are located in census tracts defined by the Brazilian Census Bureau as informal settlements (aglomerados subnormais, AGSN). Physical and demographic characteristics of AGSNs suggest that S. aureus colonization prevalence would be higher, but little is known about the prevalence of MRSA in these settings. We conducted a cross-sectional study to assess risk factors for S. aureus and MRSA colonization among children attending DCCs located in AGSN vs non-AGSN. Nasal swabs were collected from children aged three months to six years in 23 public DCCs in Niterói, Brazil between August 2011 and October 2012. Of 500 children enrolled in the study, 240 (48%) were colonized with S. aureus and 31 (6.2%) were colonized with MRSA. Children attending DCCs in AGSNs were 2.32 times more likely to be colonized with S. aureus (95% CI: 1.32, 4.08), and 3.27 times more likely to be colonized with MRSA than children attending non-AGSN DCCs (95% CI: 1.52, 7.01), adjusted for confounding variables. S. aureus and MRSA colonization prevalence among children attending DCCs in informal settlement census tracts was higher than previously reported in healthy pre-school children in Latin America. Our data suggest that transmission may occur more frequently in DCCs rather than at home, highlighting the importance of DCCs in AGSNs as potential MRSA reservoirs. This finding underscores the importance of local epidemiologic surveillance in vulnerable AGSN communities.

Molecular mechanism of TGF-β signaling pathway in colon carcinogenesis and status of curcumin as chemopreventive strategy.

PubMed

Ramamoorthi, Ganesan; Sivalingam, Nageswaran

2014-08-01

Colon cancer is one of the third most common cancer in man, the second most common cancer in women worldwide, and the second leading cause of mortality in the USA. There are a number of molecular pathways that have been implicated in colon carcinogenesis, including TGF-β/Smad signaling pathway. TGF-β (transforming growth factor-beta) signaling pathway has the potential to regulate various biological processes including cell growth, differentiation, apoptosis, extracellular matrix modeling, and immune response. TGF-β signaling pathway acts as a tumor suppressor, but alterations in TGF-β signaling pathway promotes colon cancer cell growth, migration, invasion, angiogenesis, and metastasis. Here we review the role of TGF-β signaling cascade in colon carcinogenesis and multiple molecular targets of curcumin in colon carcinogenesis. Elucidation of the molecular mechanism of curcumin on TGF-β signaling pathway-induced colon carcinogenesis may ultimately lead to novel and more effective treatments for colon cancer.

Prevalence and risk factors of infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae.

PubMed

Nakai, Hazuki; Hagihara, Mao; Kato, Hideo; Hirai, Jun; Nishiyama, Naoya; Koizumi, Yusuke; Sakanashi, Daisuke; Suematsu, Hiroyuki; Yamagishi, Yuka; Mikamo, Hiroshige

2016-05-01

To study the clinical characteristics and associated risk factors of infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. A case-control study at a large university hospital in Japan, comparing patients who were infected or colonized with ESBL-producing Enterobacteriaceae (n = 212) and non-ESBL-producing Enterobacteriaceae (n = 2089) in 2010-2013. Data were collected from medical charts, retrospectively. Multivariate logistic regression analysis was used to explore risk factors of ESBL-producing Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis) infection or colonization for each pathogen, respectively. ESBL-producing Enterobacteriaceae [E. coli (n = 113), K. oxytoca (n = 46), K. pneumoniae (n = 41), P. mirabilis (n = 12)] were taken from patients were identified in 1409 outpatient and 892 inpatients. Infection or colonization caused by ESBL-producing Enterobacteriaceae was considered to be hospital-acquired, healthcare-associated and community-acquired in 60.4%, 17.9% and 21.7% patients, respectively. Independent risk factors for ESBL-producing Enterobacteriaceae infection or colonization were male sex, cerebrovascular disease, intubation/tracheostomy, major surgery within 60 days (p < 0.001). Moreover, antimicrobial usage (more than 4 days) during preceding 60 days, especially aminoglycoside, oxazolidinone, tetracycline, fluoroquinolone, trimethoprim/sulfamethoxazole, and second- and fourth-generation cephalosporin were risk factors (p < 0.001). However, acquisition location of infection (hospital-acquired and community-onset) was not a risk factor (p > 0.05). The problem of ESBL production is no longer limited to hospital-acquired infections. The presence of chronic illness, such as cerebrovascular disease, and recent antimicrobial use were independent risk factors for ESBL-producing Enterobacteriaceae infection or colonization. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Quality indicators for colorectal cancer surgery and care according to patient-, tumor-, and hospital-related factors.

PubMed

Mathoulin-Pélissier, Simone; Bécouarn, Yves; Belleannée, Geneviève; Pinon, Elodie; Jaffré, Anne; Coureau, Gaëlle; Auby, Dominique; Renaud-Salis, Jean-Louis; Rullier, Eric

2012-07-19

Colorectal cancer (CRC) care has improved considerably, particularly since the implementation of a quality of care program centered on national evidence-based guidelines. Formal quality assessment is however still needed. The aim of this research was to identify factors associated with practice variation in CRC patient care. CRC patients identified from all cancer centers in South-West France were included. We investigated variations in practices (from diagnosis to surgery), and compliance with recommended guidelines for colon and rectal cancer. We identified factors associated with three colon cancer practice variations potentially linked to better survival: examination of ≥ 12 lymph nodes (LN), non-use and use of adjuvant chemotherapy for stage II and stage III patients, respectively. We included 1,206 patients, 825 (68%) with colon and 381 (32%) with rectal cancer, from 53 hospitals. Compliance was high for resection, pathology report, LN examination, and chemotherapy use for stage III patients. In colon cancer, 26% of stage II patients received adjuvant chemotherapy and 71% of stage III patients. 84% of stage US T3T4 rectal cancer patients received pre-operative radiotherapy. In colon cancer, factors associated with examination of ≥ 12 LNs were: lower ECOG score, advanced stage and larger hospital volume; factors negatively associated were: left sided tumor location and one hospital district. Use of chemotherapy in stage II patients was associated with younger age, advanced stage, emergency setting and care structure (private and location); whereas under-use in stage III patients was associated with advanced age, presence of comorbidities and private hospitals. Although some changes in practices may have occurred since this observational study, these findings represent the most recent report on practices in CRC in this region, and offer a useful methodological approach for assessing quality of care. Guideline compliance was high, although some organizational factors such as hospital size or location influence practice variation. These factors should be the focus of any future guideline implementation.

Analysis of 162 colon injuries in patients with penetrating abdominal trauma: concomitant stomach injury results in a higher rate of infection.

PubMed

O'Neill, Patricia A; Kirton, Orlando C; Dresner, Lisa S; Tortella, Bartholomew; Kestner, Mark M

2004-02-01

Fecal contamination from colon injury has been thought to be the most significant factor for the development of surgical site infection (SSI) after trauma. However, there are increasing data to suggest that other factors may play a role in the development of postinjury infection in patients after colon injury. The purpose of this study was to determine the impact of gastric wounding on the development of SSI and nonsurgical site infection (NSSI) in patients with colon injury. Post hoc analysis was performed on data prospectively collected for 317 patients presenting with penetrating hollow viscus injury. One hundred sixty-two patients with colon injury were subdivided into one of three groups: patients with isolated colon wounds (C), patients with colon and stomach wounds with or without other organ injury (C+S), and patients with colon and other organ injury but no stomach injury (C-S) and assessed for the development of SSI and NSSI. Infection rates were also determined for patients who sustained isolated gastric injury (S) and gastric injury in combination with other injuries other than colon (S-C). Penetrating Abdominal Trauma Index, operative times, and transfusion were assessed. Discrete variables were analyzed by Cochran-Mantel-Haenszel chi2 test and Fisher's exact test. Risk factor analysis was performed by multivariate logistic regression. C+S patients had a higher rate of SSI infection (31%) than C patients (3.6%) (p=0.008) and C-S patients (13%) (p=0.021). Similarly, the incidence of NSSI was also significantly greater in the C+S group (37%) compared with the C patients (7.5%) (p=0.07) and the C-S patients (17%) (p=0.019). There was no difference in the rate of SSI or NSSI between the C and C-S groups (p=0.3 and p=0.24, respectively). The rate of SSI was significantly greater in the C+S patients when compared with the S-C patients (31% vs. 10%, p=0.008), but there was no statistical difference in the rate of NSSI in the C+S group and the S-C group (37% vs. 24%, p=0.15). The addition of a gastric injury to a colon injury has a synergistic effect on the rate of postoperative infection.

Seasonality of vesicular-arbuscular mycorrhizae in sedges in a semi-arid tropical grassland

NASA Astrophysics Data System (ADS)

Muthukumar, T.; Udaiyan, K.

2002-10-01

Vesicular-arbuscular mycorrhizal (VAM) colonization and spore numbers in the rhizosphere of Cyperus iria L. and C. rotundus L., growing in a semi-arid tropical grassland, was studied during the 1993 and 1994 monsoons. In addition, climatic and chemical properties of the soils were determined in order to investigate their influence on mycorrhizal variables. VAM fungal association in the sedges was confirmed by plant- and root-trap culture techniques. The soil nutrients exhibited seasonal variations, but were highly variable between years. Intercellular hyphae and vesicles with occasional intraradical spores characterized mycorrhizal association in sedges. Dark septate fungi also colonized roots of sedges. Temporal variations in mycorrhizal colonization and spore numbers occurred, indicating seasonality. However, the patterns of mycorrhizal colonization and spore numbers were different during both the years. The VAM fungal structures observed were intercellular hyphae and vesicles. Changes in the proportion of root length with VAM structures, total colonization levels and spore numbers were related to climatic and edaphic factors. However, the intensity of influence of climatic and soil factors on VAM tended to vary with sedge species.

High-Throughput Sequencing of Campylobacter jejuni Insertion Mutant Libraries Reveals mapA as a Fitness Factor for Chicken Colonization

PubMed Central

Johnson, Jeremiah G.; Livny, Jonathan

2014-01-01

Campylobacter jejuni is a leading cause of gastrointestinal infections worldwide, due primarily to its ability to asymptomatically colonize the gastrointestinal tracts of agriculturally relevant animals, including chickens. Infection often occurs following consumption of meat that was contaminated by C. jejuni during harvest. Because of this, much interest lies in understanding the mechanisms that allow C. jejuni to colonize the chicken gastrointestinal tract. To address this, we generated a C. jejuni transposon mutant library that is amenable to insertion sequencing and introduced this mutant pool into day-of-hatch chicks. Following deep sequencing of C. jejuni mutants in the cecal outputs, several novel factors required for efficient colonization of the chicken gastrointestinal tract were identified, including the predicted outer membrane protein MapA. A mutant strain lacking mapA was constructed and found to be significantly reduced for chicken colonization in both competitive infections and monoinfections. Further, we found that mapA is required for in vitro competition with wild-type C. jejuni but is dispensable for growth in monoculture. PMID:24633877

High-throughput sequencing of Campylobacter jejuni insertion mutant libraries reveals mapA as a fitness factor for chicken colonization.

PubMed

Johnson, Jeremiah G; Livny, Jonathan; Dirita, Victor J

2014-06-01

Campylobacter jejuni is a leading cause of gastrointestinal infections worldwide, due primarily to its ability to asymptomatically colonize the gastrointestinal tracts of agriculturally relevant animals, including chickens. Infection often occurs following consumption of meat that was contaminated by C. jejuni during harvest. Because of this, much interest lies in understanding the mechanisms that allow C. jejuni to colonize the chicken gastrointestinal tract. To address this, we generated a C. jejuni transposon mutant library that is amenable to insertion sequencing and introduced this mutant pool into day-of-hatch chicks. Following deep sequencing of C. jejuni mutants in the cecal outputs, several novel factors required for efficient colonization of the chicken gastrointestinal tract were identified, including the predicted outer membrane protein MapA. A mutant strain lacking mapA was constructed and found to be significantly reduced for chicken colonization in both competitive infections and monoinfections. Further, we found that mapA is required for in vitro competition with wild-type C. jejuni but is dispensable for growth in monoculture.

Novel anti-angiogenic effects of formononetin in human colon cancer cells and tumor xenograft.

PubMed

Auyeung, Kathy Ka-Wai; Law, Pui-Ching; Ko, Joshua Ka-Shun

2012-12-01

Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus, a medicinal plant that possesses antitumorigenic properties. Our previous findings demonstrated that formononetin initiates growth-inhibitory and pro-apoptotic activities in human colon cancer cells. In the present study, we aimed to further examine the potential of formononetin in controlling angiogenesis and tumor cell invasiveness in human colon cancer cells and tumor xenografts. The results showed that formononetin downregulated the expression of the key pro-angiogenic factors, including vascular endothelial growth factor (VEGF) and matrix metalloproteinases. We also discovered that the invasiveness of metastatic colon cancer cells was alleviated following drug treatment. The potential anti-angiogenic effect of formononetin was examined in nude mouse xenografts. The tumor size and the number of proliferating cells were reduced in the tumor tissues obtained from the formononetin-treated group. The serum VEGF level was also reduced in the drug-treated animals when compared to the controls. These findings suggest that formononetin inhibits angiogenesis and tumor cell invasion, and thus support its use in the treatment of advanced and metastatic colon cancers.

Methicillin-resistant Staphylococcus aureus colonization, behavioral risk factors, and skin and soft-tissue infection at an ambulatory clinic serving a large population of HIV-infected men who have sex with men.

PubMed

Szumowski, John D; Wener, Kenneth M; Gold, Howard S; Wong, Michael; Venkataraman, Lata; Runde, Carrie A; Cohen, Daniel E; Mayer, Kenneth H; Wright, Sharon B

2009-07-01

We conducted a prospective cohort study of 795 outpatients, many of whom were human immunodeficiency virus-infected men who have sex with men, to characterize risk of skin and soft-tissue infection (SSTI) associated with methicillin-resistant Staphylococcus aureus (MRSA) nares and perianal colonization. Multivariate analysis revealed that perianal colonization, drug use, and prior SSTIs were strongly associated with development of an SSTI. Of the patients who were colonized with MRSA at study entry, 36.7% developed an SSTI during the ensuing 12 months, compared with 8.1% of persons who were not colonized with MRSA.

Group B Streptococci Colonization in Pregnant Guatemalan Women: Prevalence, Risk Factors, and Vaginal Microbiome.

PubMed

Rick, Anne-Marie; Aguilar, Angie; Cortes, Rosita; Gordillo, Remei; Melgar, Mario; Samayoa-Reyes, Gabriela; Frank, Daniel N; Asturias, Edwin J

2017-01-01

Infection causes 1 of every 5 neonatal deaths globally. Group B Streptococcus (GBS) is the most significant pathogen, although little is known about its epidemiology and risk in low-income countries. A cross-sectional study in 2015 at a public hospital in Guatemala City enrolled women ≥35 weeks' gestation. Vaginal and rectal swabs were processed using Lim broth and GBS CHROMagar then agglutination testing. Risk factors were assessed using multivariate analysis. Vaginal microbiota were profiled by 16S ribosomal ribonucleic acid sequencing in a subset of 94 women. Of 896 pregnant women, 155 (17.3%; 95% confidence interval [CI], 14.9-19.9) were GBS colonized. Colonization was associated with history of previous infant with poor outcome (odds ratio [OR], 1.94; 95% CI, 1.15-3.27) and increasing maternal age (OR, 1.05; 95% CI, 1.02-1.09). Multiparity was protective (OR, .39; 95% CI, .21-.72). Four (6%) GBS-exposed infants had early-onset neonatal sepsis. Vaginal microbiome composition was associated with previous antibiotic exposure ( P = .003) and previous low birth weight infant ( P = .03), but not GBS colonization ( P = .72). Several individual taxa differed in abundance between colonized and noncolonized women. Group B Streptococcus is prevalent in pregnant women from Guatemala with different risk factors than previously described. Although the vaginal microbiome was not altered significantly in GBS-colonized women, use of antibiotics had an effect on its composition. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Type 1 fimbriae contribute to catheter-associated urinary tract infections caused by Escherichia coli.

PubMed

Reisner, Andreas; Maierl, Mario; Jörger, Michael; Krause, Robert; Berger, Daniela; Haid, Andrea; Tesic, Dijana; Zechner, Ellen L

2014-03-01

Biofilm formation on catheters is thought to contribute to persistence of catheter-associated urinary tract infections (CAUTI), which represent the most frequent nosocomial infections. Knowledge of genetic factors for catheter colonization is limited, since their role has not been assessed using physicochemical conditions prevailing in a catheterized human bladder. The current study aimed to combine data from a dynamic catheterized bladder model in vitro with in vivo expression analysis for understanding molecular factors relevant for CAUTI caused by Escherichia coli. By application of the in vitro model that mirrors the physicochemical environment during human infection, we found that an E. coli K-12 mutant defective in type 1 fimbriae, but not isogenic mutants lacking flagella or antigen 43, was outcompeted by the wild-type strain during prolonged catheter colonization. The importance of type 1 fimbriae for catheter colonization was verified using a fimA mutant of uropathogenic E. coli strain CFT073 with human and artificial urine. Orientation of the invertible element (IE) controlling type 1 fimbrial expression in bacterial populations harvested from the colonized catheterized bladder in vitro suggested that the vast majority of catheter-colonizing cells (up to 88%) express type 1 fimbriae. Analysis of IE orientation in E. coli populations harvested from patient catheters revealed that a median level of ∼73% of cells from nine samples have switched on type 1 fimbrial expression. This study supports the utility of the dynamic catheterized bladder model for analyzing catheter colonization factors and highlights a role for type 1 fimbriae during CAUTI.

Monoclonal antibodies against colonization factor antigen I pili from enterotoxigenic Escherichia coli.

PubMed

Worobec, E A; Shastry, P; Smart, W; Bradley, R; Singh, B; Paranchych, W

1983-09-01

Hybridomas secreting monoclonal antibodies directed against intact colonization factor antigen I pili have been produced by the fusion of spleen cells from immunized BALB/c mice with NS1/SP2 myeloma cells. The four monoclones with the highest antibody titer, as detected by enzyme-linked immunosorbant assay (ELISA), were chosen for antibody amplification by production of mouse ascitic fluid. These four were examined for antibody specificity by ELISA and immunoblot assays, using six different pilus types. Three of the four monoclonal isolates were specific for only colonization factor antigen I pili in both assays, whereas the remaining isolate showed a distinct cross-reactivity with K99 pili in the ELISA assay but not in immunoblot analysis. These results indicate that this monoclone may be recognizing a common structural element between the two adhesive pilus types.

Monoclonal antibodies against colonization factor antigen I pili from enterotoxigenic Escherichia coli.

PubMed Central

Worobec, E A; Shastry, P; Smart, W; Bradley, R; Singh, B; Paranchych, W

1983-01-01

Hybridomas secreting monoclonal antibodies directed against intact colonization factor antigen I pili have been produced by the fusion of spleen cells from immunized BALB/c mice with NS1/SP2 myeloma cells. The four monoclones with the highest antibody titer, as detected by enzyme-linked immunosorbant assay (ELISA), were chosen for antibody amplification by production of mouse ascitic fluid. These four were examined for antibody specificity by ELISA and immunoblot assays, using six different pilus types. Three of the four monoclonal isolates were specific for only colonization factor antigen I pili in both assays, whereas the remaining isolate showed a distinct cross-reactivity with K99 pili in the ELISA assay but not in immunoblot analysis. These results indicate that this monoclone may be recognizing a common structural element between the two adhesive pilus types. Images PMID:6136463

Primary repair vs. colostomy in colon injuries.

PubMed

Robles-Castillo, Javier; Murillo-Zolezzi, Adrián; Murakami, Pablo Daniel; Silva-Velasco, Jorge

2009-01-01

Colon trauma is frequent and its prevalence is difficult to establish because of the different factors that intervene in its origin. In Mexico, traumatic colon injuries, albeit stab wounds or gunshot wounds, are on the rise. Our objective was to evaluate the most appropriate management for traumatic colon injuries. We conducted a retrospective study of 178 case files of patients with abdominal trauma and colon lesions during a 5-year period from January 2003 to June 2008 from the General Hospital of Balbuena, Mexico City. The study compared the use of primary closure vs. colostomy, analyzing variables such as sex, age, type of wound, severity of lesion and mortality. There were a total of 178 patients; 156 were male (87.6%) and 22 were female (12.4%). The most affected age group was between 21 and 30 years; 74 patients (41.6%) had stab wounds and 104 patients (58.4%) had gunshot wounds. Management consisted mainly of primary closure in 92 cases (51.7%) vs. colostomy in 86 patients (48.3%). However, 64% of gunshot wounds were treated with colostomy. Reported mortality was 9.55% and this was due to different factors such as multiple organ injury. Treatment of traumatic colon injury should be case specific, taking into account the mechanism of the lesion, its severity and associated injuries.

Ursolic acid protects against ulcerative colitis via anti-inflammatory and antioxidant effects in mice.

PubMed

Liu, Baohai; Piao, Xuehua; Guo, Lianyi; Liu, Shanshan; Chai, Fang; Gao, Leming

2016-06-01

Ursolic acid (UA) has been reported to have a protective effect in colitis. However, the underlying mechanisms remain to be elucidated. In the present study, experimental ulcerative colitis was induced in male BALB/c mice by the administration of 5% dextran sulfate sodium (DSS) for 7 days, followed by treatment with UA for another 7 days. Hematoxylin & eosin staining was performed to evaluate colon tissue damage, and enzyme assays were used to measure malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in colon homogenate. In addition, serum levels of interleukin (IL)‑1β and tumor necrosis factor (TNF)‑α were measured using an ELISA, and the level of nuclear factor (NF)‑κB p65 in the colonic tissues was assessed by western blotting. The 7‑day DSS administration induced marked colon damage, increased the serum levels of IL‑1β and TNF‑α, increased MDA content and decreased SOD activity in the colon homogenate. These changes were significantly improved by treatment with UA. UA also reduced the DSS‑stimulated high nuclear level of NF‑κB p65 in the colon tissues. These results demonstrate a protective role of UA in ulcerative colitis, and suggest that anti-inflammatory and antioxidant activities are involved in the underlying mechanisms.

Travel-acquired ESBL-producing Enterobacteriaceae: impact of colonization at individual and community level.

PubMed

Woerther, Paul-Louis; Andremont, Antoine; Kantele, Anu

2017-04-01

Antibiotic resistance is a rapidly increasing global emergency that calls for action from all of society. Intestinal multidrugresistant (MDR) bacteria have spread worldwide with extended-spectrum beta-lactamase (ESBL) -producing Enterobacteriaceae (ESBL-PE) as the most prevalent type. The millions of travelers annually visiting regions with poor hygiene contribute substantially to this spread. Our review explores the underlying data and discusses the consequences of the colonization. PubMed was searched for relevant literature between January 2010 and August 2016. We focused on articles reporting (1) the rate of ESBL-PE acquisition in a group of travelers recruited before/after international travel, (2) fecal carriage of ESBL-PE as explored by culture and, for part of the studies, (3) analysis of factors predisposing to colonization. We reviewed a total of 16 studies focusing on travel-acquired ESBL-PE. The acquisition rates reveal that 2070% of visitors to (sub)tropical regions get colonized by ESBL-PE. The main risk factors predisposing to colonization during travel are destination, travelers diarrhea, and antibiotic use. While most of those colonized remain asymptomatic, acquisition of ESBL-PE may have consequences both at individual and community level. We discuss current efforts to restrict the spread. © International Society of Travel Medicine, 2017. Published by Oxford University Press.

Travel-acquired ESBL-producing Enterobacteriaceae: impact of colonization at individual and community level

PubMed Central

Woerther, Paul-Louis; Andremont, Antoine

2017-01-01

Abstract Background: Antibiotic resistance is a rapidly increasing global emergency that calls for action from all of society. Intestinal multidrugresistant (MDR) bacteria have spread worldwide with extended-spectrum beta-lactamase (ESBL) -producing Enterobacteriaceae (ESBL-PE) as the most prevalent type. The millions of travelers annually visiting regions with poor hygiene contribute substantially to this spread. Our review explores the underlying data and discusses the consequences of the colonization. Methods: PubMed was searched for relevant literature between January 2010 and August 2016. We focused on articles reporting (1) the rate of ESBL-PE acquisition in a group of travelers recruited before/after international travel, (2) fecal carriage of ESBL-PE as explored by culture and, for part of the studies, (3) analysis of factors predisposing to colonization. Results: We reviewed a total of 16 studies focusing on travel-acquired ESBL-PE. The acquisition rates reveal that 2070% of visitors to (sub)tropical regions get colonized by ESBL-PE. The main risk factors predisposing to colonization during travel are destination, travelers diarrhea, and antibiotic use. Conclusions: While most of those colonized remain asymptomatic, acquisition of ESBL-PE may have consequences both at individual and community level. We discuss current efforts to restrict the spread. PMID:28520999

Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

PubMed Central

Brown, Aisling F.; Leech, John M.; Rogers, Thomas R.; McLoughlin, Rachel M.

2014-01-01

In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity. PMID:24409186

Rheumatoid-like arthritis associated with a colonic carcinoma.

PubMed

Simon, R D; Ford, L E

1980-05-01

A 76-year-old woman with rapidly progressive athritis associated with a rising rheumatoid factor, acute joint effusion, and fever had remission of her symptoms and return of her laboratory values to normal following removal of a colonic carcinoma.

Targeting of Escherichia coli F4 fimbriae to Fcgamma receptors enhances the maturation of porcine dendritic cells.

PubMed

Devriendt, Bert; Verdonck, Frank; Summerfield, Artur; Goddeeris, Bruno M; Cox, Eric

2010-06-15

F4(+) enterotoxigenic Escherichia coli (ETEC) infections are an important cause of postweaning diarrhoea in piglets and an oral immunization of piglets with purified F4 fimbriae protects them from a subsequent F4(+) ETEC infection. However, oral immunization of suckling piglets is hampered due to the immature status of their immune system. Targeting of antigens to Fcgamma receptors (FcgammaR) on human and murine dendritic cells (DC) has been shown to enhance DC maturation and both humoral and cellular immune responses. To investigate the effect of F4 fimbriae incorporated in immune complexes (F4-IC) on porcine DC, we used porcine monocytic-derived DC (MoDC) as a model system. The results in this study demonstrate that FcgammaRI, II and III mRNA is expressed by porcine MoDC. Furthermore, we show that FcgammaRII and III are expressed on the cell surface and that F4-IC are internalized by MoDC via FcgammaR. This FcgammaR ligation induced a significantly enhanced expression of Major Histocompatibility complex (MHCII) class II and the costimulatory molecules CD80/86 and CD40 by MoDC compared with immature MoDC. Furthermore, the phagocytic capacity of F4-IC stimulated MoDC was reduced as evidenced by a reduced uptake of DQ-ovalbumin and FITC-dextran. In an allogenic and autologous mixed lymphocyte reaction, these F4-IC-activated MoDC showed an improved T cell stimulatory capacity in comparison with immature MoDC. The F4-IC induced DC maturation correlated with significant higher expression levels of several pro-inflammatory cytokines such as interleukine (IL) 1beta, IL-6 and Tumor necrosis factor alpha, the chemokine IL-8 and IL-12p40 in comparison with immature MoDC. Altogether, these results clearly demonstrate that FcgammaR engagement enhances the maturation of porcine MoDC, which may suggest that antigen targeting to FcgammaR on DC could improve vaccine design against infections. Copyright 2009 Elsevier B.V. All rights reserved.

What causes female bias in the secondary sex ratios of the dioecious woody shrub Salix sitchensis colonizing a primary successional landscape?

Treesearch

C. Che-Castaldo; C. M. Crisafulli; J. G. Bishop; W. F. Fagan

2015-01-01

PREMISE OF THE STUDY: Females often outnumber males in Salix populations, although the mechanisms behind female bias are not well understood and could be caused by both genetic and ecological factors. We investigated several ecological factors that could bias secondary sex ratios of Salix sitchensis colonizing Mount St. Helens after the 1980 eruption.M ETHODS...

Predictors for gut colonization of carbapenem-resistant Enterobacteriaceae in neonates in a neonatal intensive care unit.

PubMed

Singh, Narendra Pal; Choudhury, Debapriya Das; Gupta, Kavita; Rai, Sumit; Batra, Prerna; Manchanda, Vikas; Saha, Rituparna; Kaur, I R

2018-06-01

With the emergence of carbapenem-resistant isolates, the therapeutic alternatives have become limited. Various factors are responsible for carbapenem-resistant Enterobacteriaceae (CRE) gut colonization. This study was conducted to determine predictors for CRE gut colonization in neonates who were hospital delivered and admitted in a neonatal intensive care unit (NICU). Three rectal swabs were collected from 300 hospital-delivered and NICU-admitted neonates (likely to stay for >3 days). The data collected for the possible risk factors for CRE gut colonization were namely mode of delivery, prolonged rupture of membrane >18 hours, period of gestation, birth weight, meconium-stained liquor, ventilation, intravenous catheter, nasogastric (NG) tube, NG feeding, breastfeeding, katori spoon feeding, top feeding, expressed breastmilk, antibiotics administration, and duration of hospitalization. P < .05 was considered as statistically significant. A total of 26 cases of CRE were isolated from 300 neonates. Statistically significant risk factors were found to be NG tube, breastfeeding, NG feeding, top feeding, expressed breastmilk, ventilation, antibiotic administration, and duration of hospitalization. Top feeding and antibiotics administration were identified as 2 independent risk factors by multiple logistic regression. Active surveillance of cultures from hospitalized patients and implementation of preventive efforts can reduce the risk of CRE. Copyright © 2018. Published by Elsevier Inc.

The Increasing Challenge of Multidrug-Resistant Gram-Negative Bacilli

PubMed Central

Giuffrè, Mario; Geraci, Daniela M.; Bonura, Celestino; Saporito, Laura; Graziano, Giorgio; Insinga, Vincenzo; Aleo, Aurora; Vecchio, Davide; Mammina, Caterina

2016-01-01

Abstract Colonization and infection by multidrug-resistant gram-negative bacilli (MDR GNB) in neonatal intensive care units (NICUs) are increasingly reported. We conducted a 5-year prospective cohort surveillance study in a tertiary NICU of the hospital “Paolo Giaccone,” Palermo, Italy. Our objectives were to describe incidence and trends of MDR GNB colonization and the characteristics of the most prevalent organisms and to identify the risk factors for colonization. Demographic, clinical, and microbiological data were prospectively collected. Active surveillance cultures (ASCs) were obtained weekly. Clusters of colonization by extended spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae were analyzed by conventional and molecular epidemiological tools. During the study period, 1152 infants were enrolled in the study. Prevalences of colonization by MDR GNB, ESBL-producing GNB and multiple species/genera averaged, respectively, 28.8%, 11.7%, and 3.7%. Prevalence and incidence density of colonization by MDR GNB and ESBL-producing GNB showed an upward trend through the surveillance period. Rates of ESBL-producing E coli and K pneumoniae colonization showed wide fluctuations peaking over the last 2 years. The only independent variables associated with colonization by MDR GNB and ESBL-producing organisms and multiple colonization were, respectively, the days of NICU stay (odds ratio [OR] 1.041), the days of exposure to ampicillin–sulbactam (OR 1.040), and the days of formula feeding (OR 1.031). Most clusters of E coli and K pneumoniae colonization were associated with different lineages. Ten out of 12 clusters had an outborn infant as their index case. Our study confirms that MDR GNB are an increasing challenge to NICUs. The universal once-a-week approach allowed us to understand the epidemiology of MDR GNB, to timely detect new clones and institute contact precautions, and to assess risk factors. Collection of these data can be an important tool to optimize antimicrobials use and control the emergence and dissemination of resistances in NICU. PMID:26962817

Evaluation of intermittent preventive treatment of malaria against group B Streptococcus colonization in pregnant women: a nested analysis of a randomized controlled clinical trial of sulfadoxine/pyrimethamine versus mefloquine.

PubMed

Capan-Melser, Mesküre; Mombo Ngoma, Ghyslain; Akerey-Diop, Daisy; Basra, Arti; Würbel, Heike; Groger, Mirjam; Mackanga, Jean R; Zoleko-Manego, Rella; Schipulle, Ulla; Schwing, Julia; Lötsch, Felix; Rehman, Khalid; Matsiegui, Pierre-Blaise; Agnandji, Selidji T; Adegnika, Ayôla A; Bélard, Sabine; González, Raquel; Kremsner, Peter G; Menendez, Clara; Ramharter, Michael

2015-01-01

Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Africa. Sulfadoxine/pyrimethamine-the current intermittent preventive treatment of malaria in pregnancy (IPTp)-has proven in vitro activity against group B Streptococcus (GBS). Because of specific drug resistance to sulfadoxine/pyrimethamine, mefloquine-an antimalarial without in vitro activity against GBS-was evaluated as a potential alternative. This study assessed the potential of sulfadoxine/pyrimethamine-IPTp to reduce the prevalence of GBS colonization in pregnant women in Gabon when compared with the inactive control mefloquine-IPTp. Pregnant women participating in a randomized controlled clinical trial evaluating mefloquine-IPTp versus sulfadoxine/pyrimethamine-IPTp were invited to participate and recto-vaginal swabs were collected at delivery for detection of GBS colonization. Prevalence of recto-vaginal GBS colonization was compared between IPTp regimens and risk factor and birth outcome analyses were computed. Among 549 participants, 106 were positive for GBS colonization at delivery (19%; 95% CI = 16%-23%). Prevalence of maternal GBS colonization showed no significant difference between the two IPTp regimens (mefloquine-IPTp: 67 of 366 women = 18%; 95% CI = 14%-22%; sulfadoxine/pyrimethamine-IPTp: 39 of 183 women = 21%; 95% CI = 15%-27%). Risk factor analysis for GBS colonization demonstrated a significant association with illiteracy (adjusted OR = 2.03; 95% CI = 1.25-3.30). GBS colonization had no impact on birth outcome, anaemia at delivery, gestational age and birth weight. Sulfadoxine/pyrimethamine did not reduce colonization rates when used as the IPTp drug during pregnancy. Illiteracy was associated with GBS colonization. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Identification of Population Bottlenecks and Colonization Factors during Assembly of Bacterial Communities within the Zebrafish Intestine

PubMed Central

Wiles, Travis J.; Martinez, Emily S.; Jemielita, Matthew; Burns, Adam R.; Parthasarathy, Raghuveer; Bohannan, Brendan J. M.

2015-01-01

ABSTRACT The zebrafish, Danio rerio, is a powerful model for studying bacterial colonization of the vertebrate intestine, but the genes required by commensal bacteria to colonize the zebrafish gut have not yet been interrogated on a genome-wide level. Here we apply a high-throughput transposon mutagenesis screen to Aeromonas veronii Hm21 and Vibrio sp. strain ZWU0020 during their colonization of the zebrafish intestine alone and in competition with each other, as well as in different colonization orders. We use these transposon-tagged libraries to track bacterial population sizes in different colonization regimes and to identify gene functions required during these processes. We show that intraspecific, but not interspecific, competition with a previously established bacterial population greatly reduces the ability of these two bacterial species to colonize. Further, using a simple binomial sampling model, we show that under conditions of interspecific competition, genes required for colonization cannot be identified because of the population bottleneck experienced by the second colonizer. When bacteria colonize the intestine alone or at the same time as the other species, we find shared suites of functional requirements for colonization by the two species, including a prominent role for chemotaxis and motility, regardless of the presence of another species. PMID:26507229

Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation on Tumor-Associated Endothelial Cells Leads to Treatment of Orthotopic Human Colon Cancer in Nude Mice1

PubMed Central

Sasaki, Takamitsu; Kitadai, Yasuhiko; Nakamura, Toru; Kim, Jang-Seong; Tsan, Rachel Z; Kuwai, Toshio; Langley, Robert R; Fan, Dominic; Kim, Sun-Jin; Fidler, Isaiah J

2007-01-01

The purpose of our study was to determine whether the dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways in tumor-associated endothelial cells can inhibit the progressive growth of human colon carcinoma in the cecum of nude mice. SW620CE2 human colon cancer cells growing in culture and orthotopically in the cecum of nude mice expressed a high level of transforming growth factor alpha (TGF-α) and vascular endothelial growth factor (VEGF) but were negative for EGFR, human epidermal growth factor receptor 2 (HER2), and VEGFR. Double immunofluorescence staining revealed that tumor-associated endothelial cells expressed EGFR, VEGFR2, phosphorylated EGFR (pEGFR), and phosphorylated VEGFR (pVEGFR). Treatment of mice with either 7H-pyrrolo [2,3-d]-pyrimidine lead scaffold (AEE788; an inhibitor of EGFR and VEGFR tyrosine kinase) or CPT-11 as single agents significantly inhibited the growth of cecal tumors (P < .01); this decrease was even more pronounced with AEE788 combined with CPT-11 (P < .001). AEE788 alone or combined with CPT-11 also inhibited the expression of pEGFR and pVEGFR on tumor-associated endothelial cells, significantly decreased vascularization and tumor cell proliferation, and increased the level of apoptosis in both tumor-associated endothelial cells and tumor cells. These data demonstrate that targeting EGFR and VEGFR signaling on tumor-associated endothelial cells provides a viable approach for the treatment of colon cancer. PMID:18084614

Location in the right hemi-colon is an independent risk factor for delayed post-polypectomy hemorrhage: a multi-center case-control study.

PubMed

Buddingh, K Tim; Herngreen, Thomas; Haringsma, Jelle; van der Zwet, Wil C; Vleggaar, Frank P; Breumelhof, Ronald; Ter Borg, Frank

2011-06-01

Delayed hemorrhage is an infrequent, but serious complication of colonoscopic polypectomy. Large size is the only polyp-related factor that has been unequivocally proven to increase the risk of delayed bleeding. It has been suggested that location in the right hemi-colon is also a risk factor. The objective of this study was to determine whether polyp location is an independent risk factor for delayed post-polypectomy hemorrhage. A retrospective case-control study was conducted in two university hospitals and two community hospitals. Thirty-nine cases and 117 controls were identified. In multivariate analysis, size and location were found to be independent polyp-related risk factors for delayed type hemorrhage. The risk increased by 13% for every 1 mm increase in polyp diameter (odds ratio (OR) 1.13, 95% confidence interval (CI) 1.05-1.20, P<0.001). Polyps located in the right hemi-colon had an OR of 4.67 (1.88-11.61, P=0.001) for delayed hemorrhage. Polyps in the cecum seemed to be especially at high risk in univariate analysis (OR 13.82, 95% CI 2.66-71.73), but this could not be assessed in multivariate analysis as the number of cases was too small. Polyp type (sessile or pedunculated) was not a risk factor. Polyp location in the right hemi-colon seems to be an independent and substantial risk factor for delayed post-polypectomy hemorrhage. A low threshold for preventive hemostatic measures is advised when removing polyps from this region.

Impact of urban contamination of the La Paz River basin on thermotolerant coliform density and occurrence of multiple antibiotic resistant enteric pathogens in river water, irrigated soil and fresh vegetables.

PubMed

Poma, Violeta; Mamani, Nataniel; Iñiguez, Volga

2016-01-01

La Paz River in Andean highlands is heavily polluted with urban run-off and further contaminates agricultural lowlands and downstream waters at the Amazon watershed. Agricultural produce at this region is the main source of vegetables for the major Andean cities of La Paz and El Alto. We conducted a 1 year study, to evaluate microbial quality parameters and occurrence of multiple enteropathogenic bacteria (Enterohemorrhagic E. coli-EHEC, Enteroinvasive E. coli or Shigella-EIEC/Shigella, Enteroaggregative E. coli-EAEC, Enteropathogenic E. coli-EPEC Enterotoxigenic E. coli-ETEC and Salmonella) and its resistance to 11 antibiotics. Four sampling locations were selected: a fresh mountain water reservoir (un-impacted, site 1) and downstream sites receiving wastewater discharges (impacted, sites 2-4). River water (sites 1-4, N = 48), and soil and vegetable samples (site 3, N = 24) were collected during dry (April-September) and rainy seasons (October-March). Throughout the study, thermotolerant coliform density values at impacted sites greatly exceeded the guidelines for recreational and agricultural water uses. Seasonal differences were found for thermotolerant coliform density during dry season in water samples nearby a populated and hospital compound area. In contrast to the un-impacted site, where none of the tested enteropathogens were found, 100 % of surface water, 83 % of soil and 67 % of vegetable samples at impacted sites, were contaminated with at least one enteropathogen, being ETEC and Salmonella the most frequently found. ETEC isolates displayed different patterns of toxin genes among sites. The occurrence of enteropathogens was associated with the thermotolerant coliform density. At impacted sites, multiple enteropathogens were frequently found during rainy season. Among isolated enteropathogens, 50 % were resistant to at least two antibiotics, with resistance to ampicillin, nalidixic acid, trimethoprim-sulfamethoxazole and tetracycline commonly present. Moreover, some Salmonella isolates were distinguished by their multi-resistance to ≥8 antibiotics, within soil and vegetable samples. Overall, this study demonstrates that La Paz River-an affluent of the Amazon macrobasin-is heavily polluted along the year with a high density of thermotolerant coliforms and is a reservoir of multiple antibiotic resistant enteropathogens, present in river water, soil and vegetables. These data highlight health risk associated with food and waterborne diseases at the region.

Outbreak of resistant Acinetobacter baumannii- measures and proposal for prevention and control.

PubMed

Romanelli, Roberta Maia de Castro; Jesus, Lenize Adriana de; Clemente, Wanessa Trindade; Lima, Stella Sala Soares; Rezende, Edna Maria; Coutinho, Rosane Luiza; Moreira, Ricardo Luiz Fontes; Neves, Francelli Aparecida Cordeiro; Brás, Nelma de Jesus

2009-10-01

Acinetobacter baumannii colonization and infection, frequent in Intensive Care Unit (ICU) patients, is commonly associated with high morbimortality. Several outbreaks due to multidrug-resistant (MDR) A. baumanii have been reported but few of them in Brazil. This study aimed to identify risk factors associated with colonization and infection by MDR and carbapenem-resistant A. baumannii strains isolated from patients admitted to the adult ICU at HC/UFMG. A case-control study was performed from January 2007 to June 2008. Cases were defined as patients colonized or infected by MDR/carbapenem-resistant A. baumannii, and controls were patients without MDR/carbapenem-resistant A. baumannii isolation, in a 1:2 proportion. For statistical analysis, due to changes in infection control guidelines, infection criteria and the notification process, this study was divided into two periods. During the first period analyzed, from January to December 2007, colonization or infection by MDR/carbapenem-resistant A. baumannii was associated with prior infection, invasive device utilization, prior carbapenem use and clinical severity. In the multivariate analysis, prior infection and mechanical ventilation proved to be statistically significant risk factors. Carbapenem use showed a tendency towards a statistical association. During the second study period, from January to June 2008, variables with a significant association with MDR/carbapenem-resistant A. baumannii colonization/infection were catheter utilization, carbapenem and third-generation cephalosporin use, hepatic transplantation, and clinical severity. In the multivariate analysis, only CVC use showed a statistical difference. Carbapenem and third-generation cephalosporin use displayed a tendency to be risk factors. Risk factors must be focused on infection control and prevention measures considering A. baumanni dissemination.

Late-onset neonatal sepsis, risk factors and interventions: an analysis of recurrent outbreaks of Serratia marcescens, 2006-2011.

PubMed

Samuelsson, A; Isaksson, B; Hanberger, H; Olhager, E

2014-01-01

Between 2006 and 2011, 11 patients with Serratia marcescens sepsis and 47 patients colonized due to the spread of various clones were observed. These recurrent clusters brought about interventions to reduce spread between patients. To evaluate the effect of stepwise interventions to prevent S. marcescens colonization/sepsis and to analyse risk factors for late-onset sepsis (LOS). An open retrospective observational study was performed to evaluate the interventions. A retrospective case-control study was performed to analyse the risk factors for LOS. S. marcescens sepsis and colonization decreased after the stepwise adoption of hygiene interventions. Low gestational age, low birth weight, indwelling central venous or umbilical catheter, and ventilator treatment were identified as risk factors for LOS. Compliance with basic hygiene guidelines was the only intervention monitored continuously from late 2007. Compliance increased gradually to a steady high level in early 2009. There was a decrease in S. marcescens LOS, clustering after the second quarter of 2008. After the first quarter of 2009, S. marcescens colonization decreased. It was not possible to identify the specific effects of each intervention, but it is likely that an update of the hospital's antibiotic policy affected the occurrence of S. marcescens LOS. The delayed effect of interventions on S. marcescens colonization was probably due to the time it takes for new routines to have an effect, illustrated by the gradual increase in compliance with basic hygiene guidelines. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Colonic gas explosion during therapeutic colonoscopy with electrocautery

PubMed Central

Ladas, Spiros D; Karamanolis, George; Ben-Soussan, Emmanuel

2007-01-01

Therapeutic colonoscopy with electrocautery is widely used around the world. Adequate colonic cleansing is considered a crucial factor for the safety of this procedure. Colonic gas explosion, although rare, is one of the most frightening iatrogenic complications during colonoscopy with electrocautery. This complication is the result of an accumulation of colonic gases to explosive concentrations, but may be prevented by meticulous bowel preparation. The purpose of this review is to discuss the indications and the types of bowel preparations for therapeutic colonoscopy, and to contribute recommendations for the adequate bowel preparation for colonoscopy with electrocautery. PMID:17879396

Preventive effects of curcumin on the development of azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db obese mice.

PubMed

Kubota, Masaya; Shimizu, Masahito; Sakai, Hiroyasu; Yasuda, Yoichi; Terakura, Daishi; Baba, Atsushi; Ohno, Tomohiko; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

2012-01-01

Obesity-related metabolic abnormalities include a state of chronic inflammation and adipocytokine imbalance, which increase the risk of colon cancer. Curcumin, a component of turmeric, exerts both cancer preventive and antiinflammatory properties. Curcumin is also expected to have the ability to reverse obesity-related metabolic derangements. The present study examined the effects of curcumin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Feeding with a diet containing 0.2% and 2.0% curcumin caused a significant reduction in the total number of colonic premalignant lesions compared with basal diet-fed mice. The expression levels of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 (COX-2) mRNAs on the colonic mucosa of AOM-treated mice were significantly decreased by curcumin administration. Dietary feeding with curcumin markedly activated AMP-activated kinase, decreased the expression of COX-2 protein, and inhibited nuclear factor-κB activity on the colonic mucosa of AOM-treated mice. Curcumin also increased the serum levels of adiponectin while conversely decreasing the serum levels of leptin and the weights of fat. In conclusion, curcumin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model, at least in part, by attenuating chronic inflammation and improving adipocytokine imbalance. Curcumin may be useful in the chemoprevention of colorectal carcinogenesis in obese individuals.

Ghrelin-induced stimulation of colonic propulsion is dependent on hypothalamic neuropeptide Y1- and corticotrophin-releasing factor 1 receptor activation.

PubMed

Tebbe, J J; Mronga, S; Tebbe, C G; Ortmann, E; Arnold, R; Schäfer, M K-H

2005-09-01

Peptides participating in the hypothalamic control of feeding behaviour are also involved in the central autonomic control of gastrointestinal functions, such as secretion and motility. An anatomical interaction and functional relationship in the central nervous system between the feeding-related peptides neuropeptide Y and ghrelin is well documented. Furthermore, it has been shown that feeding-related peptides can influence digestive function via central corticotrophin-releasing factor (CRF) pathways. In the present study, we investigated the role of ghrelin in the central autonomic control of colonic motility. Furthermore, we addressed the hypothesis that ghrelin is involved in the hypothalamic control of colonic motor function, utilizing central neuropeptide Y receptors and hypothalamic CRF pathways. Ghrelin (0.03, 0.06 and 0.12 nmol) bilaterally microinjected into the paraventricular nucleus (PVN) induced a significant stimulation of colonic propulsion. In particular, the colonic transit time decreased from 312+/-7 min to 198+/-12 min. Microinjection of the neuropeptide Y1 receptor antagonist, BIBP-3226 (200 pmol), or the nonselective CRF receptor antagonist, astressin (30 pmol), into the PVN abolished the stimulatory effect of ghrelin injected into the PVN on colonic transit time, whereas pretreatment with the selective CRF2 receptor, antisauvagine-30 (28 pmol), failed to affect the effect of PVN-ghrelin injection on colonic propulsion. These results suggest that ghrelin can act as central modulator of gastrointestinal motor functions at the level of the PVN via neuropeptide Y1- and CRF1 receptor-dependent mechanisms.

Associations of Demographic and Socioeconomic Factors with Complete Treatment and Follow-up of Colon Cancer.

PubMed

Davoudi-Monfared, Esmat; Heidarnia, Mohammad Ali; Akbari, Mohammad Esmail; Yavari, Parvin; Abadi, Alireza

2012-01-01

Cancer is the second cause of death in the world, and colon cancer is the third cause of death and is one of the most common cancers which will cure with early diagnosis, treatment and sufficient follow up. Assessing factors which affect this cancer is important for prolonging patient survival. Socioeconomic factors are among effective factors of cancer morbidity and mortality. Because mortality rates for colon cancers vary by socioeconomic characteristics, this study has been performed to recognize the relationship between socioeconomic factors with treatment and follow up of colon cancer. This was a cross-sectional, descriptive study for patients with colon cancer registered in Cancer Research Center of Shahid Beheshti University of Medical Sciences from April 2005 to November 2006. Patients were selected randomly, and the study was conducted using questionnaires filled by interviewing the patients via phone (if a patient was dead, the questions were asked from their family members). Data analysis was done using SPSS (version 19) software. The study was performed on 520 colon cancer patients with age range of 23-88 years. The mean age of the patients was 63 (S.D.=11.8) and the median age was 64. Two hundred thirty seven (45.4%) patients were female and 283 (54.4%) were male. Using Chi-square test, age<60 (p=0.002) and female gender (p=0.034) had a significant correlation with complete treatment and there was a significant relationship between complete follow up and age<60 (p=0.037), academic education (p=0.02) and having insurance (p=0.021). Multiple logistic regression tests were used to evaluate concurrent effects of variables on treatment and follow up. Correlated variables to complete treatment include: age<60 (p=0.001), and female gender The Odds Ratio (OR) of completing treatment for patients under 60 years of age versus patients above 60 years was 3.13 (95% C.I. 1.55 to 6.34), and the OR of completing treatment for women versus men was 1.91(95% C.I. 1.33 to 2.74). Correlated variables to follow up were academic education ( ) and having insurance . The OR of cancer follow up in illiterate patients versus college-educated patients was 0.45 (95% C.I. 0.24 to 0.82), and the OR of cancer follow up in patients without insurance versus patients with health was 0.46 (95% C.I. 0.21 to 0.98). Age is a correlated factor on completing colon cancer treatment. Women have more complete colon cancer treatment than men. Academic education and having insurance were the most important factors among socioeconomic factors observed in a five-year follow up after treatment. As the population of the old is increasing, executing effective interventions to improve treatment and follow up procedures for old patients is of prime importance. It seems that increasing the insurance contribution in follow up measures may lead to increase in the regular follow up and may affect patients' survival.

Opposite Role of Tumor Necrosis Factor Receptors in Dextran Sulfate Sodium-Induced Colitis in Mice

PubMed Central

Wang, Yi; Liu, Guijun; Wang, Renxi; Xiao, He; Li, Xinying; Hou, Chunmei; Shen, Beifen; Guo, Renfeng; Li, Yan; Shi, Yanchun; Chen, Guojiang

2012-01-01

Tumor necrosis factor-α (TNF-α) is a key factor for the pathogenesis of inflammatory bowel diseases (IBD), whose function is known to be mediated by TNF receptor 1 (TNFR1) or 2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, acute colitis was induced by dextran sulfate sodium (DSS) instillation in TNFR1 or 2−/− mice. TNFR1 ablation led to exacerbation of signs of colitis, including more weight loss, increased mortality, colon shortening and oedema, severe intestinal damage, and higher levels of myeloperoxidase compared to wild-type counterparts. While, TNFR2 deficiency had opposite effects. This discrepancy was reflected by alteration of proinflammatory cytokine and chemokine production in the colons. Importantly, TNFR1 ablation rendered enhanced apoptosis of colonic epithelial cells and TNFR2 deficiency conferred pro-apoptotic effects of lamina propria (LP)-immune cells, as shown by the decreased ratio of Bcl-2/Bax and enhanced nuclear factor (NF)-κB activity. PMID:23285227

Pre-Clinical Testing of Real-Time PCR Assays for Diarrheal Disease Agents of Genera Escherichia and Shigella

DTIC Science & Technology

2014-05-16

FOR DIARRHEAL DISEASE AGENTS OF GENERA ESCHERICHIA AND SHIGELLA May 16, 2014 Reporting Period: October 1, 2010 to September 30, 2013...10-2010 - 30-09-2013 PRE-CLINICAL TESTING OF REAL-TIME PCR ASSAYS FOR DIARRHEAL DISEASE AGENTS OF GENERA ESCHERICHIA AND SHIGELLA ...Texas (MOA 2007 - 2013. Agreement No.: DODI 4000.19; AFI 25-201). Pre-clinical test results qualify ETEC and Shigella real-time PCR assays as lead

Prevalence of multi-antimicrobial-agent resistant, shiga toxin and enterotoxin producing Escherichia coli in surface waters of river Ganga.

PubMed

Ram, Siya; Vajpayee, Poornima; Shanker, Rishi

2007-11-01

The consumption of polluted surface water for domestic and recreational purposes by large populations in developing nations is a major cause of diarrheal disease related mortality. The river Ganga and its tributaries meet 40% of the water requirement for drinking and irrigation in India. In this study, Escherichia coli isolates (n=75) of the river Ganga water were investigated for resistance to antimicrobial agents (n=15) and virulence genes specific to shiga toxin (STEC) and enterotoxin producing E. coli (ETEC). E. coli isolates from the river Ganga water exhibit resistance to multiple antimicrobial agents. The distribution of antimicrobial agent resistance in E. colivaries significantly (chi2: 81.28 at df = 24, p < 0.001) between the sites. Both stx1 and stx2 genes were present in 82.3% of STEC (n=17) while remaining isolates possess either stxl (11.8%) or stx2 (5.9%). The presence of eaeA, hlyA, and chuA genes was observed in 70.6, 88.2, and 58.8% of STEC, respectively. Both LT1 and ST1 genes were positive in 66.7% of ETEC (n=15) while 33.3% of isolates harbor only LT1 gene. The prevalence of multi-antimicrobial-agent resistant E. coli in the river Ganga water poses increased risk of infections in the human population.

Fusion/Astrophysics Teacher Research Academy

NASA Astrophysics Data System (ADS)

Correll, Donald

2005-10-01

In order to engage California high school science teachers in the area of plasma physics and fusion research, LLNL's Fusion Energy Program has partnered with the UC Davis Edward Teller Education Center, ETEC (http://etec.ucdavis.edu), the Stanford University Solar Center (http://solar-center.stanford.edu) and LLNL's Science / Technology Education Program, STEP (http://education.llnl.gov). A four-level ``Fusion & Astrophysics Research Academy'' has been designed to give teachers experience in conducting research using spectroscopy with their students. Spectroscopy, and its relationship to atomic physics and electromagnetism, provides for an ideal plasma `bridge' to the CA Science Education Standards (http://www.cde.ca.gov/be/st/ss/scphysics.asp). Teachers attend multiple-day professional development workshops to explore new research activities for use in the high school science classroom. A Level I, 3-day program consists of two days where teachers learn how plasma researchers use spectrometers followed by instructions on how to use a research grade spectrometer for their own investigations. A 3rd day includes touring LLNL's SSPX (http://www.mfescience.org/sspx/) facility to see spectrometry being used to measure plasma properties. Spectrometry classroom kits are made available for loaning to participating teachers. Level I workshop results (http://education.llnl.gov/fusion&_slash;astro/) will be presented along with plans being developed for Level II (one week advanced SKA's), Level III (pre-internship), and Level IV (summer internship) research academies.

Expression and immunogenicity of an Escherichia coli K99 fimbriae subunit antigen in soybean.

PubMed

Piller, Kenneth J; Clemente, Thomas E; Jun, Sang Mu; Petty, Cynthia C; Sato, Shirley; Pascual, David W; Bost, Kenneth L

2005-09-01

Enterotoxigenic Escherichia coli (ETEC) cause acute diarrhea in humans and farm animals, and can be fatal if the host is left untreated. As a potential alternative to traditional needle vaccination of cattle, we investigated the feasibility of expressing the major K99 fimbrial subunit, FanC, in soybean (Glycine max) for use as an edible subunit vaccine. As a first step in this developmental process, a synthetic version of fanC was optimized for expression in the cytosol and transferred to soybean via Agrobacterium-mediated transformation. Western analysis of T(0) events revealed the presence of a peptide with the expected mobility for FanC in transgenic protein extracts, and immunofluorescense confirmed localization to the cytosol. Two T(0) lines, which accumulated FanC to levels near 0.5% of total soluble protein, were chosen for further molecular characterization in the T(1) and T(2) generations. Mice immunized intraperitoneally with protein extract derived from transgenic leaves expressing synthetic FanC developed significant antibody titers against bacterially derived FanC and produced antigen-specific CD4(+) T lymphocytes, demonstrating the ability of transgenic FanC to function as an immunogen. These experiments are the first to demonstrate the expression and immunogenicity of a model subunit antigen in the soybean system, and mark the first steps toward the development of a K99 edible vaccine to protect against ETEC.

Binding determinants in the interplay between porcine aminopeptidase N and enterotoxigenic Escherichia coli F4 fimbriae.

PubMed

Xia, Pengpeng; Quan, Guomei; Yang, Yi; Zhao, Jing; Wang, Yiting; Zhou, Mingxu; Hardwidge, Philip R; Zhu, Jianzhong; Liu, Siguo; Zhu, Guoqiang

2018-02-26

The binding of F4 + enterotoxigenic Escherichia coli (ETEC) and the specific receptor on porcine intestinal epithelial cells is the initial step in F4 + ETEC infection. Porcine aminopeptidase N (APN) is a newly discovered receptor for F4 fimbriae that binds directly to FaeG adhesin, which is the major subunit of the F4 fimbriae variants F4ab, F4ac, and F4ad. We used overlapping peptide assays to map the APN-FaeG binding sites, which has facilitated in the identifying the APN-binding amino acids that are located in the same region of FaeG variants, thereby limiting the major binding regions of APN to 13 peptides. To determine the core sequence motif, a panel of FaeG peptides with point mutations and FaeG mutants were constructed. Pull-down and binding reactivity assays using piglet intestines determined that the amino acids G159 of F4ab, N209 and L212 of F4ac, and A200 of F4ad were the critical residues for APN binding of FaeG. We further show using ELISA and confocal microscopy assay that amino acids 553-568, and 652-670 of the APN comprise the linear epitope for FaeG binding in all three F4 fimbriae variants.

GT-094, a NO-NSAID, inhibits colon cancer cell growth by activation of a reactive oxygen species-microRNA-27a: ZBTB10-specificity protein pathway.

PubMed

Pathi, Satya S; Jutooru, Indira; Chadalapaka, Gayathri; Sreevalsan, Sandeep; Anand, S; Thatcher, Gregory Rj; Safe, Stephen

2011-02-01

Ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094) is a novel nitric oxide (NO) chimera containing an nonsteroidal anti-inflammatory drug (NSAID) and NO moieties and also a disulfide pharmacophore that in itself exhibits cancer chemopreventive activity. In this study, the effects and mechanism of action of GT-094 were investigated in RKO and SW480 colon cancer cells. GT-094 inhibited cell proliferation and induced apoptosis in both cell lines and this was accompanied by decreased mitochondrial membrane potential (MMP) and induction of reactive oxygen species (ROS), and these responses were reversed after cotreatment with the antioxidant glutathione. GT-094 also downregulated genes associated with cell growth [cyclin D1, hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor (EGFR)], survival (bcl-2, survivin), and angiogenesis [VEGF and its receptors (VEGFR1 and VEGFR2)]. Results of previous RNA interference studies in this laboratory has shown that these genes are regulated, in part, by specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4 that are overexpressed in colon and other cancer cell lines and not surprisingly, GT-094 also decreased Sp1, Sp3, and Sp4 in colon cancer cells. GT-094-mediated repression of Sp and Sp-regulated gene products was due to downregulation of microRNA-27a (miR-27a) and induction of ZBTB10, an Sp repressor that is regulated by miR-27a in colon cancer cells. Moreover, the effects of GT-094 on Sp1, Sp3, Sp4, miR-27a, and ZBTB10 were also inhibited by glutathione suggesting that the anticancer activity of GT-094 in colon cancer cells is due, in part, to activation of an ROS-miR-27a:ZBTB10-Sp transcription factor pathway.

Colonization and demographic expansion of freshwater fauna across the Hawaiian archipelago.

PubMed

Alda, F; Gagne, R B; Walter, R P; Hogan, J D; Moody, K N; Zink, F; McIntyre, P B; Gilliam, J F; Blum, M J

2016-10-01

It is widely accepted that insular terrestrial biodiversity progresses with island age because colonization and diversification proceed over time. Here, we assessed whether this principle extends to oceanic island streams. We examined rangewide mtDNA sequence variation in four stream-dwelling species across the Hawaiian archipelago to characterize the relationship between colonization and demographic expansion, and to determine whether either factor reflects island age. We found that colonization and demographic expansion are not related and that neither corresponds to island age. The snail Neritina granosa exhibited the oldest colonization time (~2.713 mya) and time since demographic expansion (~282 kya), likely reflecting a preference for lotic habitats most prevalent on young islands. Conversely, gobioid fishes (Awaous stamineus, Eleotris sandwicensis and Sicyopterus stimpsoni) colonized the archipelago only ~0.411-0.935 mya, suggesting ecological opportunities for colonization in this group were temporally constrained. These findings indicate that stream communities form across colonization windows, underscoring the importance of ecological opportunities in shaping island freshwater diversity. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization.

PubMed

Aymeric, Laetitia; Donnadieu, Françoise; Mulet, Céline; du Merle, Laurence; Nigro, Giulia; Saffarian, Azadeh; Bérard, Marion; Poyart, Claire; Robine, Sylvie; Regnault, Béatrice; Trieu-Cuot, Patrick; Sansonetti, Philippe J; Dramsi, Shaynoor

2018-01-09

Colonization by Streptococcus gallolyticus subsp. gallolyticus (SGG) is strongly associated with the occurrence of colorectal cancer (CRC). However, the factors leading to its successful colonization are unknown, and whether SGG influences the oncogenic process or benefits from the tumor-prone environment to prevail remains an open question. Here, we elucidate crucial steps that explain how CRC favors SGG colonization. By using mice genetically prone to CRC, we show that SGG colonization is 1,000-fold higher in tumor-bearing mice than in normal mice. This selective advantage occurs at the expense of resident intestinal enterococci. An SGG-specific locus encoding a bacteriocin ("gallocin") is shown to kill enterococci in vitro. Importantly, bile acids strongly enhance this bacteriocin activity in vivo, leading to greater SGG colonization. Constitutive activation of the Wnt pathway, one of the earliest signaling alterations in CRC, and the decreased expression of the bile acid apical transporter gene Slc10A2 , as an effect of the Apc founding mutation, may thereby sustain intestinal colonization by SGG. We conclude that CRC-specific conditions promote SGG colonization of the gut by replacing commensal enterococci in their niche.

Teat apex colonization with coagulase-negative Staphylococcus species before parturition: Distribution and species-specific risk factors.

PubMed

De Visscher, A; Piepers, S; Haesebrouck, F; De Vliegher, S

2016-02-01

Coagulase-negative staphylococci (CNS) are the main cause of bovine intramammary infections and are also abundantly present in extramammary habitats such as teat apices. Teat apex colonization (TAC) with CNS has already been explored in lactating dairy cows at the species level, whereas this is not true for dry cows and end-term heifers. Therefore, the aim of this observational study was to describe CNS TAC in nonlactating dairy cows and end-term heifers in Flemish dairy herds and to identify associated risk factors at the herd, cow, and quarter level. All CNS were molecularly identified to the species level using transfer RNA intergenic spacer PCR (tDNA-PCR) and sequencing of the 16S rRNA gene, allowing for species-specific statistical analyses using multivariable, multilevel logistic regression. Staphylococcus devriesei, Staphylococcus chromogenes, Staphylococcus haemolyticus, and Staphylococcus equorum were the most frequently isolated species. Staphylococcus chromogenes was the sole species colonizing teat apices of cows and heifers in all herds, whereas large between-herd differences were observed for the other species. Teat apices of red and white Holstein Friesians, of quarters dried off without an internal teat sealer, and swabbed in months with lower precipitation and higher ambient temperature were significantly more likely to be colonized by S. devriesei. Slightly dirty teat apices and teat apices swabbed in months with lower precipitation had higher odds of being colonized by S. chromogenes, whereas teat apices sampled in months with lower precipitation and higher ambient temperature were more likely to be colonized by S. haemolyticus. Dirty teat apices and teat apices swabbed in months with lower ambient temperature in combination with low precipitation had higher odds of being colonized by S. equorum. Diverse factors explaining CNS TAC, yet mostly related to humidity, ambient temperature, and hygiene, substantiate differences in epidemiological behavior and ecology between species. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors

PubMed Central

2014-01-01

Background Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined. To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. Methods A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. Results P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. Conclusions The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis. PMID:24964956

Who's on First? Part II: Bacterial and fungal colonization of fresh soil minerals

NASA Astrophysics Data System (ADS)

Whitman, T.; Neurath, R.; Zhang, P.; Yuan, T.; Weber, P. K.; Zhou, J.; Pett-Ridge, J.; Firestone, M. K.

2015-12-01

Soil organic matter (SOM) stabilization by soil minerals is an important mechanism influencing soil C cycling. Microbes make up only a few percent of total SOM, but have a disproportionate impact on SOM cycling. Their direct interactions with soil minerals, however, are not well characterized. We studied colonization of fresh minerals by soil microbes in an Avena barbata (wild oat) California grassland soil microcosm. Examining quartz, ferrihydrite, kaolinite, and the heavy fraction of the native soil, we asked: (1) Do different minerals select for different communities, or do random processes drive the colonization of fresh minerals? (2) What factors influence which taxa colonize fresh minerals? After incubating mesh bags (<18 μm) of minerals buried next to actively growing plant roots for 2 months, we used high-throughput sequencing of 16S and ITS2 genes to characterize the microbial communities colonizing the minerals. We found significant differences between the microbial community composition of different minerals and soil for both bacteria and fungi. We found a higher relative abundance of arbuscular mycorrhial fungi with ferrihydrite and quartz, and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging of these minerals suggests that some fungal hyphae are moving C directly from roots to mineral surfaces. The enriched presence of both nematode-associated fungi (Pochonia sp.) and bacteria (Candidatus Xiphinematobacter) in the minerals suggests that these minerals may be a habitat for nematodes. Bacteria of the family Chitinophagaceae and genus Janthinobacterium were significantly enriched on both ferrihydrite and quartz minerals, both of which may interact with colonizing fungi. These findings suggest that: (1) Microbial colonization of fresh minerals is not a fully passive or neutral process. (2) Mineral exploration by plant-associated fungi and soil fauna transport may be factors in determining the initial colonization of minerals and subsequent C protection.

Role of Corticotropin-releasing Factor Signaling in Stress-related Alterations of Colonic Motility and Hyperalgesia

PubMed Central

Taché, Yvette; Million, Mulugeta

2015-01-01

The corticotropin-releasing factor (CRF) signaling systems encompass CRF and the structurally related peptide urocortin (Ucn) 1, 2, and 3 along with 2 G-protein coupled receptors, CRF1 and CRF2. CRF binds with high and moderate affinity to CRF1 and CRF2 receptors, respectively while Ucn1 is a high-affinity agonist at both receptors, and Ucn2 and Ucn3 are selective CRF2 agonists. The CRF systems are expressed in both the brain and the colon at the gene and protein levels. Experimental studies established that the activation of CRF1 pathway in the brain or the colon recaptures cardinal features of diarrhea predominant irritable bowel syndrome (IBS) (stimulation of colonic motility, activation of mast cells and serotonin, defecation/watery diarrhea, and visceral hyperalgesia). Conversely, selective CRF1 antagonists or CRF1/CRF2 antagonists, abolished or reduced exogenous CRF and stress-induced stimulation of colonic motility, defecation, diarrhea and colonic mast cell activation and visceral hyperalgesia to colorectal distention. By contrast, the CRF2 signaling in the colon dampened the CRF1 mediated stimulation of colonic motor function and visceral hyperalgesia. These data provide a conceptual framework that sustained activation of the CRF1 system at central and/or peripheral sites may be one of the underlying basis of IBS-diarrhea symptoms. While targeting these mechanisms by CRF1 antagonists provided a relevant novel therapeutic venue, so far these promising preclinical data have not translated into therapeutic use of CRF1 antagonists. Whether the existing or newly developed CRF1 antagonists will progress to therapeutic benefits for stress-sensitive diseases including IBS for a subset of patients is still a work in progress. PMID:25611064

Dietary folate does not significantly affect the intestinal microbiome, inflammation or tumorigenesis in azoxymethane-dextran sodium sulphate-treated mice.

PubMed

MacFarlane, Amanda J; Behan, Nathalie A; Matias, Fernando M G; Green, Judy; Caldwell, Don; Brooks, Stephen P J

2013-02-28

Inflammatory bowel disease (IBD) is a risk factor for the development of colon cancer. Environmental factors including diet and the microflora influence disease outcome. Folate and homocysteine have been associated with IBD-mediated colon cancer but their roles remain unclear. We used a model of chemically induced ulcerative colitis (dextran sodium sulphate (DSS)) with or without the colon carcinogen azoxymethane (AOM) to determine the impact of dietary folic acid (FA) on colonic microflora and the development of colon tumours. Male mice (n 15 per group) were fed a FA-deficient (0 mg/kg), control (2 mg/kg) or FA-supplemented (8 mg/kg) diet for 12 weeks. Folate status was dependent on the diet (P< 0·001) and colitis-induced treatment (P= 0·04) such that mice with colitis had lower circulating folate. FA had a minimal effect on tumour initiation, growth and progression, although FA-containing diets tended to be associated with a higher tumour prevalence in DSS-treated mice (7-20 v. 0%, P= 0·08) and the development of more tumours in the distal colon of AOM-treated mice (13-83% increase, P= 0·09). Folate deficiency was associated with hyperhomocysteinaemia (P< 0·001) but homocysteine negatively correlated with tumour number (r - 0·58, P= 0·02) and load (r - 0·57, P= 0·02). FA had no effect on the intestinal microflora. The present data indicate that FA intake has no or little effect on IBD or IBD-mediated colon cancer in this model and that hyperhomocysteinaemia is a biomarker of dietary status and malabsorption rather than a cause of IBD-mediated colon cancer.

Supplementation with branched-chain amino acids inhibits azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db mice.

PubMed

Shimizu, Masahito; Shirakami, Yohei; Iwasa, Junpei; Shiraki, Makoto; Yasuda, Yoichi; Hata, Kazuya; Hirose, Yoshinobu; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

2009-05-01

Obesity and related metabolic abnormalities, including insulin resistance and activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis, are risk factors for colon cancer. Supplementation with branched-chain amino acids (BCAA) reduces the risk of liver cancer in cirrhotic patients who are obese, and this has been associated with an improvement of insulin resistance. The present study examined the effects of BCAA on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) mice that were obese and had hyperinsulinemia. Male db/db mice were given 4 weekly s.c. injections of AOM (15 mg/kg of body weight) and then they were fed a diet containing 3.0% BCAA or casein, a nitrogenc content-matched control diet, for 7 weeks. Feeding with BCAA caused a significant reduction in the number of total aberrant crypt foci and beta-catenin accumulated crypts, both of which are premalignant lesions of the colon, compared with the control diet-fed groups. BCAA supplementation caused a marked decrease in the expression of IGF-IR, the phosphorylated form of IGF-IR, phosphorylated glycogen synthase kinase 3beta, phosphorylated Akt, and cyclooxygenase-2 proteins on the colonic mucosa of AOM-treated mice. The serum levels of insulin, IGF-I, IGF-II, triglyceride, total cholesterol, and leptin were also decreased by supplementation with BCAA. BCAA supplementation in diet improves insulin resistance and inhibits the activation of the IGF/IGF-IR axis, thereby preventing the development of colonic premalignancies in an obesity-related colon cancer model that was also associated with hyperlipidemia and hyperinsulinemia. BCAA, therefore, may be a useful chemoprevention modality for colon cancer in obese people.

Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship.

PubMed

Noni, M; Katelari, A; Dimopoulos, G; Doudounakis, S-E; Tzoumaka-Bakoula, C; Spoulou, V

2015-11-01

Aspergillus fumigatus is commonly found in cystic fibrosis (CF) airways. Our aim was to assess the relationship between A. fumigatus chronic colonization and lung function in CF patients. A case-control study of CF patients born from 1989 to 2002 was performed. Medical records were reviewed from the time of initial diagnosis until December 2013. Chronic colonization was defined as two or more positive sputum cultures in a given year. Each patient chronically colonized with A. fumigatus was matched with three control patients (never colonized by A. fumigatus) for age, sex, and year of birth (±3 years). A number of parameters were recorded and analyzed prospectively. The primary outcome measure was the difference in forced expiratory volume in 1 s (FEV1) in percent predicted between groups. Linear mixed models were used for longitudinal analyses to evaluate the relationship between A. fumigatus chronic colonization and lung function during a 7-year period and study the lung function 4 years before the time of enrollment (t0). Twenty patients had chronic colonization and were matched with 60 controls. A significant difference in lung function was detected throughout the 7-year period after adjustment for confounders (est = 8.66, p = 0.020). Four years before t0, FEV1 baseline was the only factor associated with the course of lung function (est = 0.64, p < 0.001) and was significantly different between groups (p = 0.001). In conclusion, a decreased FEV1 baseline appears to be a risk factor for chronic colonization by A. fumigatus, which, in turn, may cause a faster deterioration of lung function.

THE PREVALENCE OF COLONIC POLYPS IN PATIENTS WITH ACROMEGALY: A CASE-CONTROL, NESTED IN A COHORT COLONOSCOPIC STUDY.

PubMed

Gonzalez, Baldomero; Vargas, Guadalupe; Mendoza, Victoria; Nava, Mariana; Rojas, Moisés; Mercado, Moisés

2017-05-01

Acromegaly is associated with an increased risk of colonic polyps. The magnitude of such risk is controversial, and the characteristics that distinguish patients who develop polyps from those who do not are not well established. This study was performed to determine the prevalence of colonic polyps upon the diagnosis of acromegaly and to compare the clinical and biochemical features of patients with and without polyps. Out of 165 patients who underwent a full colonoscopy upon diagnosis of acromegaly, 53 were found to harbor colonic lesions (cases), whereas the remaining 112 were used as controls. Demographic, clinical, and biochemical characteristics were compared between the 2 groups. The prevalence of colonic polyps was 32%, with an estimated relative risk of 6.21 (95% confidence interval [CI] 4.08-9.48). Adenomatous and nonadenomatous polyps were found in 22 and 31 patients, respectively. The most common location was the descending colon. Compared to patients without polyps, subjects with polyps were somewhat older and had significantly higher insulin-like growth factor-1 (IGF-1) levels and a higher prevalence of diabetes. Upon multivariate analysis, only IGF-1 level at diagnosis remained significantly associated with colonic polyps in general and with hyperplastic polyps in particular. Acromegaly is associated with an elevated risk of developing colonic polyps, particularly, distally located hyperplastic lesions. Except for a higher IGF-1 level at diagnosis, no distinctive clinical or biochemical features can be found among those who develop polyps compared to those who do not. CI = confidence interval GH = growth hormone IGF-1 = insulin-like growth factor 1 IQR = inter-quartile range RR = relative risk ULN = upper limit of normal.

The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model.

PubMed

Jackson, R J; Smith, S D; Wadowsky, R M; DePudyt, L; Rowe, M I

1991-04-01

In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier. The newborn rabbit provides an excellent model to study these factors. Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding. This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli. New Zealand white rabbit pups (2 to 5 days old) were studied. The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated. Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation. No bacteria were isolated from the colons of all but one control animal. Translocation or systemic sepsis did not occur. Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%). Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%). Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis. This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.

Nasal colonization of Staphylococcus aureus colonal complex 5: Prevalence, influencing factors, and phenotypic and molecular characteristics in pregnant Chinese women.

PubMed

Lin, Jialing; Wu, Chuanan; Ou, Qianting; Lin, Dongxin; Zhang, Ting; Bai, Chan; Zheng, Haoqu; Ye, Jiaping; Wang, Xiaojie; Li, Ying; Ye, Xiaohua; Yao, Zhenjiang

2017-10-01

Colonal complex 5 (CC5) has been referred to as the most pandemic community-associated Staphylococcus aureus in most Asian countries. However, few studies have focused on CC5 isolates in pregnant women. The aim of this study was to determine the prevalence and phenotypic and molecular characteristics of S aureus and methicillin-resistant S aureus (MRSA) CC5 nasal colonization in pregnant Chinese women. We performed a cross-sectional study between August and November 2015 in 2 hospitals in Shenzhen, China. Pregnant women were asked to complete questionnaires, and nasal swabs were collected. Log-binomial regression models were used to explore factors influencing S aureus and MRSA nasal colonization between the CC5 and non-CC5 or non-S aureus groups. Polymerase chain reaction assays were used to detect the molecular characteristics of isolates. Overall, 2,172 pregnant women were included in this study. The prevalence of S aureus and MRSA was 25.60% (n = 556) and 5.62% (n = 122), respectively. The multilocus sequence typing of S aureus isolates was diversified. A lower frequency of daily handwashing (<7) and weekly bathing (<7) were risk factors for the prevalence of S aureus (adjusted prevalence ratio [aPR], 1.13; 95% confidence interval [CI], 1.03-1.41 and aPR, 1.22; 95% CI, 1.03-1.45) and MRSA (aPR, 1.96; 95% CI, 1.23-3.14 and aPR, 1.47; 95% CI, 1.21-2.44) nasal colonization in the CC5 groups of pregnant women. The prevalence of S aureus and MRSA nasal colonization was moderate. The molecular characteristics of S aureus and MRSA isolates indicated possible cross-transmission among multiple resources. A higher frequency of daily handwashing and weekly bathing significantly decreased the prevalence of S aureus and MRSA CC5 nasal colonization in the pregnant women. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Factors Influencing Biofilm Formation in Streams: Bacterial Colonization, Detachment and Transport

NASA Astrophysics Data System (ADS)

Leff, L.

2005-05-01

Surfaces in aquatic systems develop biofilms containing microorganisms embedded in complex extracellular matrices. Properties of the surface, water, and colonizing organisms impact biofilm formation. Biofilm features, physical disturbance, and interactions between macro- and microscopic organisms, in turn, influence detachment. In spite of the importance of biofilms, much remains unknown about factors controlling biofilms in streams and other natural environments. Experiments were conducted in the laboratory and field to examine factors influencing surface colonization, and subsequent biofilm formation, and detachment. Microscopy methods, fluorescent in situ hybridization and confocal laser microscopy, were used to examine responses, including abundance of different taxa and biofilm depth. From these experiments, we determined that different taxa differ in their colonization ability based on properties like extracellular polysaccharide production and surface features, like hydrophobicity and that water chemistry, such as magnesium concentration, plays an important role. Moreover, detachment varies among taxa and with environmental conditions and may be enhanced by activities of macrofauna. Variation in detachment, in turn, influences bacterial transport and subsequent re-attachment. Overall, examination of attachment, detachment, and interactions in biofilms allows us to begin to understand how environmental conditions may impact the function of these communities in aquatic systems.

Spatiotemporal microbiota dynamics from quantitative in vitro and in silico models of the gut

NASA Astrophysics Data System (ADS)

Hwa, Terence

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth behaviors, which ultimately dictate the gut microbiota composition. Combining measurements of bacterial growth physiology with analysis of published data on human physiology into a quantitative modeling framework, we show how hydrodynamic forces in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla in the gut. Our model quantitatively explains the observed variation of microbiota composition among healthy adults, and predicts colonic water absorption (manifested as stool consistency) and nutrient intake to be two key factors determining this composition. The model further reveals that both factors, which have been identified in recent correlative studies, exert their effects through the same mechanism: changes in colonic pH that differentially affect the growth of different bacteria. Our findings show that a predictive and mechanistic understanding of microbial ecology in the human gut is possible, and offer the hope for the rational design of intervention strategies to actively control the microbiota. This work is supported by the Bill and Melinda Gates Foundation.

DSS-induced acute colitis in C57BL/6 mice is mitigated by sulforaphane pre-treatment.

PubMed

Wagner, Anika E; Will, Olga; Sturm, Christine; Lipinski, Simone; Rosenstiel, Philip; Rimbach, Gerald

2013-12-01

The Brassica-derived isothiocyanate sulforaphane (SFN) is known to induce factor erythroid 2-related factor 2 (Nrf2), a transcription factor centrally involved in chemoprevention. Furthermore, SFN exhibits anti-inflammatory properties in vitro and in vivo. However, little is known regarding the anti-inflammatory properties of SFN in severe inflammatory phenotypes. In the present study, we tested if pre-treatment with SFN protects mice from dextran sodium sulphate (DSS)-induced colitis. C57BL/6 mice received either phosphate-buffered saline (control) or 25 mg/kg body weight (BW) SFN per os for 7 days. Subsequently, acute colitis was induced by administering 4% DSS via drinking water for 5 days and BWs, stool consistency and faecal blood loss were recorded. Following endoscopic colonoscopy, mice were sacrificed, the organs excised and spleen weights and colon lengths measured. For histopathological analysis, distal colon samples were fixed in 4% para-formaldehyde, sectioned and stained with hematoxylin/eosin. Inflammatory biomarkers were also measured in distal colon. Treatment with SFN prior to colitis induction significantly minimised both BW loss and the disease activity index compared to control mice. Furthermore, colon lengths in SFN pre-treated mice were significantly longer than in control mice. Both macroscopic and microscopic analysis of the colon revealed attenuated inflammation in SFN pre-treated animals. mRNA analysis of distal colon samples confirmed reduced expression of inflammatory markers and increased expression of Nrf2-dependent genes in SFN pre-treated mice. Our results indicate that pre-treating mice with SFN confers protection from DSS-induced colitis. These protective effects were corroborated macroscopically, microscopically and at the molecular level. © 2013.

Association between the location of diverticular disease and the irritable bowel syndrome: a multicenter study in Japan.

PubMed

Yamada, Eiji; Inamori, Masahiko; Uchida, Eri; Tanida, Emiko; Izumi, Motoyoshi; Takeshita, Kimiya; Fujii, Tetsuro; Komatsu, Kazuto; Hamanaka, Jun; Maeda, Shin; Kanesaki, Akira; Matsuhashi, Nobuyuki; Nakajima, Atsushi

2014-12-01

No previous reports have shown an association between location of diverticular disease (DD) and the irritable bowel syndrome (IBS). We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan from June 2013 to September 2013. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid colon, descending colon, and rectum. Right-sided colon was defined as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics. Patient characteristics included mean age, 64.2±12.9 years and male:female ratio, 1.62:1. Right-sided DD was identified in 21.6% of subjects. Left-sided and bilateral DD was identified in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio, 3.1; 95% confidence interval (CI): 1.4-7.1; P=0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.3-5.2; P=0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS. Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specific changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS (Trial registration # R000012739).

Presence of bone marrow micro-metastases in stage I-III colon cancer patients is associated with worse disease-free and overall survival.

PubMed

Viehl, Carsten T; Weixler, Benjamin; Guller, Ulrich; Dell-Kuster, Salome; Rosenthal, Rachel; Ramser, Michaela; Banz, Vanessa; Langer, Igor; Terracciano, Luigi; Sauter, Guido; Oertli, Daniel; Zuber, Markus

2017-05-01

The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer patients remains unclear. We conducted a prospective cohort study with long-term follow-up to evaluate the relevance of BMM as a prognostic factor for disease free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In this prospective multicenter cohort study 144 stage I-III colon cancer patients underwent bone marrow aspiration from both iliac crests prior to open oncologic resection. The bone marrow aspirates were stained with the pancytokeratin antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS and OS were analyzed using a Cox proportional hazard model and robust standard errors to account for clustering in the multicenter setting. Median overall follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients had disease recurrence and 56 (39%) patients died. After adjusting for known prognostic factors, BMM positive patients had a significantly worse DFS (hazard ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS (HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone marrow micro-metastases occur in over one third of stage I-III colon cancer patients and are a significant, independent negative prognostic factor for DFS and OS. Future trials should evaluate whether node-negative colon cancer patients with BMM benefit from adjuvant chemotherapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression.

PubMed

Zakraoui, Ons; Marcinkiewicz, Cezary; Aloui, Zohra; Othman, Houcemeddine; Grépin, Renaud; Haoues, Meriam; Essafi, Makram; Srairi-Abid, Najet; Gasmi, Ammar; Karoui, Habib; Pagès, Gilles; Essafi-Benkhadir, Khadija

2017-01-01

Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor

PubMed Central

O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C.; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J.; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G.; Moreno Munoz, Jose Antonio; Kearney, Breda; Houston, Aileen M.; O'Mahony, Caitlin; Higgins, Des G.; Shanahan, Fergus; Palva, Airi; de Vos, Willem M.; Fitzgerald, Gerald F.; Ventura, Marco; O'Toole, Paul W.; van Sinderen, Douwe

2011-01-01

Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated “tad2003.” Mutational analysis demonstrated that the tad2003 gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria. PMID:21690406

Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor.

PubMed

O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G; Munoz, Jose Antonio Moreno; Kearney, Breda; Houston, Aileen M; O'Mahony, Caitlin; Higgins, Des G; Shanahan, Fergus; Palva, Airi; de Vos, Willem M; Fitzgerald, Gerald F; Ventura, Marco; O'Toole, Paul W; van Sinderen, Douwe

2011-07-05

Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated "tad(2003)." Mutational analysis demonstrated that the tad(2003) gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria.

The early effect of dextran sodium sulfate administration on carbachol-induced short-circuit current in distal and proximal colon during colitis development.

PubMed

Hock, M; Soták, M; Kment, M; Pácha, J

2011-01-01

Increased colonic Cl(-) secretion was supposed to be a causative factor of diarrhea in inflammatory bowel diseases. Surprisingly, hyporesponsiveness to Cl(-) secretagogues was later described in inflamed colon. Our aim was to evaluate changes in secretory responses to cholinergic agonist carbachol in distal and proximal colon during colitis development, regarding secretory activity of enteric nervous system (ENS) and prostaglandins. Increased responsiveness to carbachol was observed in both distal and proximal colon after 3 days of 2 % dextran sodium sulfate (DSS) administration. It was measured in the presence of mucosal Ba(2+) to emphasize Cl(-) secretion. The described increase was abolished by combined inhibitory effect of tetrodotoxin (TTX) and indomethacin. Indomethacin also significantly reduced TTX-sensitive current. On the 7th day of colitis development responsiveness to carbachol decreased in distal colon (compared to untreated mice), but did not change in proximal colon. TTX-sensitive current did not change during colitis development, but indomethacin-sensitive current was significantly increased the 7th day. Decreased and deformed current responses to serosal Ba(2+) were observed during colitis induction, but only in proximal colon. We conclude that besides inhibitory effect of DSS on distal colon responsiveness, there is an early stimulatory effect that manifests in both distal and proximal colon.

Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha.

PubMed

Dharmani, Poonam; Strauss, Jaclyn; Ambrose, Christian; Allen-Vercoe, Emma; Chadee, Kris

2011-07-01

The etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial species Fusobacterium nucleatum is a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only live F. nucleatum induced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasive F. nucleatum isolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal that F. nucleatum may represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

Transcription factor NF-kappaB participates in regulation of epithelial cell turnover in the colon.

PubMed

Inan, M S; Tolmacheva, V; Wang, Q S; Rosenberg, D W; Giardina, C

2000-12-01

The transcription factor nuclear factor (NF)-kappaB regulates the expression of genes that can influence cell proliferation and death. Here we analyze the contribution of NF-kappaB to the regulation of epithelial cell turnover in the colon. Immunohistochemical, immunoblot, and DNA binding analyses indicate that NF-kappaB complexes change as colonocytes mature: p65-p50 complexes predominate in proliferating epithelial cells of the colon, whereas the p50-p50 dimer is prevalent in mature epithelial cells. NF-kappaB1 (p50) knockout mice were used to study the role of NF-kappaB in regulating epithelial cell turnover. Knockout animals lacked detectable NF-kappaB DNA binding activity in isolated epithelial cells and had significantly longer crypts with a more extensive proliferative zone than their wild-type counterparts (as determined by proliferating cell nuclear antigen staining and in vivo bromodeoxyuridine labeling). Gene expression profiling reveals that the NF-kappaB1 knockout mice express the potentially growth-enhancing tumor necrosis factor (TNF)-alpha and nerve growth factor-alpha genes at elevated levels, with in situ hybridization localizing some of the TNF-alpha expression to epithelial cells. TNF-alpha is NF-kappaB regulated, and its upregulation in NF-kappaB1 knockouts may result from an alleviation of p50-p50 repression. NF-kappaB complexes may therefore influence cell proliferation in the colon through their ability to selectively activate and/or repress gene expression.

Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers.

PubMed

Tängdén, Thomas; Cars, Otto; Melhus, Asa; Löwdin, Elisabeth

2010-09-01

Foreign travel has been suggested to be a risk factor for the acquisition of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. To our knowledge, this has not previously been demonstrated in a prospective study. Healthy volunteers traveling outside Northern Europe were enrolled. Rectal swabs and data on potential travel-associated risk factors were collected before and after traveling. A total of 105 volunteers were enrolled. Four of them did not complete the study, and one participant carried ESBL-producing Escherichia coli before travel. Twenty-four of 100 participants with negative pretravel samples were colonized with ESBL-producing Escherichia coli after the trip. All strains produced CTX-M enzymes, mostly CTX-M-15, and some coproduced TEM or SHV enzymes. Coresistance to several antibiotic subclasses was common. Travel to India was associated with the highest risk for the acquisition of ESBLs (88%; n = 7). Gastroenteritis during the trip was an additional risk factor (P = 0.003). Five of 21 volunteers who completed the follow-up after 6 months had persistent colonization with ESBLs. This is the first prospective study demonstrating that international travel is a major risk factor for colonization with ESBL-producing Enterobacteriaceae. Considering the high acquisition rate of 24%, it is obvious that global efforts are needed to meet the emergence and spread of CTX-M enzymes and other antimicrobial resistances.

Foreign Travel Is a Major Risk Factor for Colonization with Escherichia coli Producing CTX-M-Type Extended-Spectrum β-Lactamases: a Prospective Study with Swedish Volunteers ▿

PubMed Central

Tängdén, Thomas; Cars, Otto; Melhus, Åsa; Löwdin, Elisabeth

2010-01-01

Foreign travel has been suggested to be a risk factor for the acquisition of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. To our knowledge, this has not previously been demonstrated in a prospective study. Healthy volunteers traveling outside Northern Europe were enrolled. Rectal swabs and data on potential travel-associated risk factors were collected before and after traveling. A total of 105 volunteers were enrolled. Four of them did not complete the study, and one participant carried ESBL-producing Escherichia coli before travel. Twenty-four of 100 participants with negative pretravel samples were colonized with ESBL-producing Escherichia coli after the trip. All strains produced CTX-M enzymes, mostly CTX-M-15, and some coproduced TEM or SHV enzymes. Coresistance to several antibiotic subclasses was common. Travel to India was associated with the highest risk for the acquisition of ESBLs (88%; n = 7). Gastroenteritis during the trip was an additional risk factor (P = 0.003). Five of 21 volunteers who completed the follow-up after 6 months had persistent colonization with ESBLs. This is the first prospective study demonstrating that international travel is a major risk factor for colonization with ESBL-producing Enterobacteriaceae. Considering the high acquisition rate of 24%, it is obvious that global efforts are needed to meet the emergence and spread of CTX-M enzymes and other antimicrobial resistances. PMID:20547788

Virulence and the Environment: a Novel Role for Vibrio cholerae Toxin-Coregulated Pili in Biofilm Formation on Chitin

PubMed Central

Reguera, Gemma; Kolter, Roberto

2005-01-01

The toxin-coregulated pilus (TCP) of Vibrio cholerae is required for intestinal colonization and cholera toxin acquisition. Here we report that TCP mediates bacterial interactions required for biofilm differentiation on chitinaceous surfaces. We also show that undifferentiated TCP− biofilms have reduced ecological fitness and, thus, that chitin colonization may represent an ecological setting outside the host in which selection for a host colonization factor may take place. PMID:15866944

The Genital Tract Virulence Factor pGP3 Is Essential for Chlamydia muridarum Colonization in the Gastrointestinal Tract.

PubMed

Shao, Lili; Zhang, Tianyuan; Melero, Jose; Huang, Yumeng; Liu, Yuanjun; Liu, Quanzhong; He, Cheng; Nelson, David E; Zhong, Guangming

2018-01-01

The cryptic plasmid is essential for Chlamydia muridarum dissemination from the genital tract to the gastrointestinal (GI) tract. Following intravaginal inoculation, a C. muridarum strain deficient in plasmid-encoded pGP3 or pGP4 but not pGP5, pGP7, or pGP8 failed to spread to the mouse gastrointestinal tract, although mice infected with these strains developed productive genital tract infections. pGP3- or pGP4-deficient strains also failed to colonize the gastrointestinal tract when delivered intragastrically. pGP4 regulates pGP3, while pGP3 does not affect pGP4 expression, indicating that pGP3 is critical for C. muridarum colonization of the gastrointestinal tract. Mutants deficient in GlgA, a chromosome-encoded protein regulated by pGP4, also consistently colonized the mouse gastrointestinal tract. Interestingly, C. muridarum colonization of the gastrointestinal tract positively correlated with pathogenicity in the upper genital tract. pGP3-deficient C. muridarum strains did not induce hydrosalpinx or spread to the GI tract even when delivered to the oviduct by intrabursal inoculation. Thus, the current study not only has revealed that pGP3 is a novel chlamydial colonization factor in the gastrointestinal tract but also has laid a foundation for investigating the significance of gastrointestinal Chlamydia . Copyright © 2017 American Society for Microbiology.

Inhibition and enhancement of microbial surface colonization: the role of silicate composition

USGS Publications Warehouse

Roberts, Jennifer A.

2004-01-01

Classical treatment of cell attachment by models of filtration or coulombic attraction assumes that attachment of cells to mineral surfaces would be controlled by factors such as response to predation, collision efficiency, or coulombic attraction between the charged groups at the mineral and cell surfaces. In the study reported here, the passive model of attachment was investigated using a native microbial consortium and a variety of Al- and Fe-bearing silicates and oxides to determine if other controls, such as mineral composition, also influence the interaction between cells and surfaces. Results from in situ colonization studies in an anaerobic groundwater at pH 6.8 combined with most probable number analyses (MPN) of surface-adherent cells demonstrate that electrostatic effects dominate microbial colonization on positively charged oxide surfaces regardless of mineral composition. In contrast, on negatively charged silicate minerals and glasses, the solid phase composition is a factor in determining the extent of microbial colonization, as well as the diversity of the attached community. In particular, silicates containing more than 1.2% Al exhibit less biomass than Al-poor silicates and MPN suggests a shift in community diversity, possibly indicating Al toxicity on these surfaces. When Fe is present in the silicate, however, this trend is reversed and abundant colonization of the surface is observed. Here, microorganisms preferentially colonize those silicate surfaces that offer beneficial nutrients and avoid those that contain potentially toxic elements.

Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF-κB and STAT3 activation.

PubMed

Jin, Bo-Ram; Chung, Kyung-Sook; Cheon, Se-Yun; Lee, Minho; Hwang, Soonjae; Noh Hwang, Sam; Rhee, Ki-Jong; An, Hyo-Jin

2017-04-06

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1β, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis.

Effect of water flow and chemical environment on microbiota growth and composition in the human colon.

PubMed

Cremer, Jonas; Arnoldini, Markus; Hwa, Terence

2017-06-20

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota.

Morphological Differentiation of Colon Carcinoma Cell Lines in Rotating Wall Vessels

NASA Technical Reports Server (NTRS)

Jessup, J. M.

1994-01-01

The objectives of this project were to determine whether (1) microgravity permits unique, three-dimensional cultures of neoplastic human colon tissues and (2) this culture interaction produces novel intestinal growth and differentiation factors. The initial phase of this project tested the efficacy of simulated microgravity for the cultivation and differentiation of human colon carcinoma in rotating wall vessels (RWV's) on microcarrier beads. The RWV's simulate microgravity by randomizing the gravity vector in an aqueous medium under a low shear stress environment in unit gravity. This simulation achieves approximately a one-fifth g environment that allows cells to 'float' and form three-dimensional relationships with less shear stress than in other stirred aqueous medium bioreactors. In the second phase of this project we assessed the ability of human colon carcinoma lines to adhere to various substrates because adhesion is the first event that must occur to create three-dimensional masses. Finally, we tested growth factor production in the last phase of this project.

Effect of water flow and chemical environment on microbiota growth and composition in the human colon

PubMed Central

Cremer, Jonas; Arnoldini, Markus; Hwa, Terence

2017-01-01

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota. PMID:28588144

Clinical and molecular epidemiology of Escherichia coli sequence type 131 among hospitalized patients colonized intestinally with fluoroquinolone-resistant E. coli.

PubMed

Han, Jennifer H; Johnston, Brian; Nachamkin, Irving; Tolomeo, Pam; Bilker, Warren B; Mao, Xiangqun; Clabots, Connie; Lautenbach, Ebbing; Johnson, James R

2014-11-01

This study examined molecular and epidemiologic factors associated with Escherichia coli sequence type 131 (ST131) among hospitalized patients colonized intestinally with fluoroquinolone (FQ)-resistant E. coli between 2002 and 2004. Among 86 patients, 21 (24%) were colonized with ST131. The proportion of ST131 isolates among colonizing isolates increased significantly over time, from 8% in 2002 to 50% in 2004 (P = 0.003). Furthermore, all 19 clonally related isolates were ST131. Future studies should identify potential transmissibility differences between ST131 and non-ST131 strains. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The role of colonization in the dynamics of patchy populations of a cyclic vole species.

PubMed

Glorvigen, Petter; Gundersen, Gry; Andreassen, Harry P; Ims, Rolf A

2013-09-01

The crash phase of vole populations with cyclic dynamics regularly leads to vast areas of uninhabited habitats. Yet although the capacity for cyclic voles to re-colonize such empty space is likely to be large and predicted to have become evolved as a distinct life history trait, the processes of colonization and its effect on the spatio-temporal dynamics have been little studied. Here we report from an experiment with root voles (Microtus oeconomus) specifically targeted at quantifying the process of colonization of empty patches from distant source patches and its resultant effect on local vole deme size variation in a patchy landscape. Three experimental factors: habitat quality, predation risk and inter-patch distance were employed among 24 habitat patches in a 100 × 300-m experimental area. The first-born cohort in the spring efficiently colonized almost all empty patches irrespective of the degree of patch isolation and predation risk, but this was dependent on habitat quality. Just after the initial colonization wave the deme sizes in patches of the same quality were underdispersed relative to Poisson variance, indicating regulated (density-dependent) settlement. Towards the end of the breeding season local demographic processes acted to smooth out the initial post-colonization differences among source and colonization patches, and among patches of initially different quality. However, at this time demographic stochasticity had also given rise to a large (overdispersed) variation in deme sizes that may have contributed to an overshadowing of the effect of other factors. The results of this experiment confirmed our expectation that the space-filling capacity of voles is large. The costs associated with transience appeared to be so low, at least at the spatial scale considered in this experiment, that such costs are not likely to substantially constrain habitat selection and colonization in the increase phase of cyclic patchy populations.

Methicillin-resistant Staphylococcus aureus in HIV patients: risk factors associated with colonization and/or infection and methods for characterization of isolates - a systematic review.

PubMed

Ferreira, Dennis de Carvalho; Silva, Glaucilene Rodrigues da; Cavalcante, Fernanda Sampaio; Carmo, Flavia Lima do; Fernandes, Leonardo Alexandre; Moreira, Suelen; Passos, Mauro Romero Leal; Colombo, Ana Paula Vieira; Santos, Katia Regina Netto dos

2014-11-01

Staphylococcus aureus is an important cause of infections and HIV-infected individuals are frequently susceptible to this pathogen. The aim of this study was to perform a systematic review to identify both the risk factors associated with colonization/infection by methicillin-resistant S. aureus in HIV patients and the methods used for characterization of isolates. An electronic search of articles published between January 2001 and December 2013 was first conducted. Among 116 studies categorized as being at a quality level of A, B or C, only 9 studies were considered to have high methodological quality (level A). The majority of these studies were retrospective (4/9 studies). The risk factors associated with colonization/infection by S. aureus were use of antimicrobials (4/9 studies), previous hospitalization (4/9 studies) and low CD4+ T lymphocyte counts (<200 cells/μl) (3/9 studies). Culture in mannitol salt agar (3/9 studies) and the latex agglutination test (5/9 studies) were the main methods used for bacterial phenotypic identification. Genotypic profiles were accessed by pulsed-field gel electrophoresis (6/9 studies) and USA300 was the most prevalent lineage (5/9 studies). Most isolates were resistant to erythromycin (3/9 studies) and susceptible to vancomycin (4/9 studies). Ultimately, use of antimicrobials and previous hospitalization were the main risk factors for colonization/infection by methicillin-resistant S. aureus in HIV-infected individuals. However, the numbers of evaluated patients, the exclusion and inclusion criteria and the characterization of the S. aureus isolates were not uniform, which made it difficult to establish the characteristics associated with HIV patients who are colonized/infected by S. aureus.

Short communication: risk factors for methicillin-resistant Staphylococcus aureus colonization among HIV patients at hospital admission.

PubMed

Lee, Linda K; Win, Mar Kyaw; Veeraraghavan, Meyyur A; Wong, Chia Siong; Chow, Angela L; Leo, Yee-Sin

2013-05-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen that has become increasingly prominent in hospitals and the community. HIV-positive patients may be one of the most MRSA-susceptible populations because of their immunocompromised status. At the Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, we implemented a universal MRSA screening program and performed a case-control study to identify risk factors for MRSA colonization among 294 HIV patients at admission from January 2009 to January 2010. Among 54 HIV-positive patients who were MRSA positive at hospital admission, 16 (29.6%) were positive at the nares/axilla/groin (NAG; one combined swab), 14 (25.9%) were NAG and perianal positive, 3 (5.6%) were NAG and throat positive, 10 (18.5%) were NAG, perianal, and throat positive, 6 (11.1%) were throat positive, and 5 (9.3%) were perianal positive. Upon multivariate analysis, we found that age [odds ratio (OR)=1.04, 95% confidence interval (CI): 1.01-1.07, p=0.006] and CD4 count <200/μl within the past 6 months (OR=4.29, 95% CI: 1.83-10.06, p=0.001) were significant risk factors for MRSA colonization. We generated a receiver operating characteristic curve using these two variables and found that the area under the curve was 0.69, indicating that age and CD4 count <200/μl performed moderately well in discriminating between those with MRSA colonization and those without. The results of our study indicate that HIV patients of older age and reduced CD4 count may have increased risk of MRSA colonization. These risk factors may serve as indicators for cohorting or isolating HIV patients at hospital admission.

The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells.

PubMed

Zacharopoulou, Nefeli; Tsapara, Anna; Kallergi, Galatea; Schmid, Evi; Alkahtani, Saad; Alarifi, Saud; Tsichlis, Philip N; Kampranis, Sotirios C; Stournaras, Christos

2018-05-14

The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins. We report here that KDM2B regulates EZH2 and BMI1 in HCT116 colon tumor cells. Knockdown of this epigenetic factor induced potent up-regulation of the protein levels of the epithelial markers E-cadherin and ZO-1, while the mesenchymal marker N-cadherin was downregulated. On the other hand, KDM2B overexpression downregulated the levels of both epithelial markers and upregulated the mesenchymal marker, suggesting control of EMT by KDM2B. In addition, RhoA, RhoB and RhoC protein levels diminished upon KDM2B-knockdown, while all three small GTPases became upregulated in KDM2B-overexpressing HCT116 cell clones. Interestingly, Rac1 GTPase level increased upon KDM2B-knockdown and diminished in KDM2B-overexpressing HCT116 colon tumor- and DU-145 prostate cancer cells. These results establish a clear functional role of the epigenetic factor KDM2B in the regulation of EMT and small-GTPases expression in colon tumor cells and further support the recently postulated oncogenic role of this histone demethylase in various tumors. © 2018 The Author(s). Published by S. Karger AG, Basel.

High frequency of multi drug resistant Gram-negative rods in two neonatal intensive care units in the Philippines

PubMed Central

Litzow, JM; Gill, CJ; Mantaring, JBV; Fox, M; Mendoza, M; Mendoza, S; Scobie, R; Huskins, WC; Goldman, DA; Hamer, DH

2013-01-01

Background Though hospital-acquired infections appear to be a growing threat to newborn survival in the developing world, the epidemiology of this problem remains poorly characterized. Methods Over a 10 month period, we conducted prospective longitudinal surveillance for colonization and bloodstream infections with Gram-negative rods (GNRs) among all infants admitted to the two largest neonatal intensive care units (NICUs) in Manila, the Philippines, determined antibiotic sensitivities, and calculated adjusted odds ratios (OR) for factors for bacteremia using multivariate logistic regression. Results Among 1,831 neonates enrolled over a 10-month period, 1017 (55%) became newly colonized and 358 (19.6%) became bacteremic with a resistant GNR, most commonly Klebsiella species, Enterobacter species, Acinetobacter species, and Pseudomonas aeruginosa. The proportion of invasive isolates with antibiotic resistance was: imipenem 20%, trimethoprim-sulfamethoxazole 41%, amikacin 52%, ampicillin/sulbactam 63%, ceftazidime 67%, and tobramycin 80%. Factors significantly associated with increased risk of bacteremia were mechanical ventilation and prematurity. Additionally, colonization with a resistant GNR was an independent risk for bacteremia. (OR 1.4, 95% CI 1.0 – 1.9) Conclusions Colonization with a resistant GNR was an independent risk factor for sepsis. If our data are typical, the unusually high intensity of colonization pressure and disease with multidrug-resistant GNRs at these two NICUs constitutes an emerging health care crisis in the developing world. Improved infection control methods are therefore critically needed in developing country settings. PMID:19435448

Ogilvie's syndrome in a case of myxedema coma.

PubMed

Yanamandra, Uday; Kotwal, Narendra; Menon, Anil; Nair, Velu

2012-05-01

Ogilvie's syndrome [acute colonic pseudo-obstruction (ACPO)] presents as massive colonic dilatation without a mechanical cause, usually in critically ill patients due to imbalanced sympathetic and parasympathetic activity. The initial therapy remains conservative with supportive measures (correction of metabolic, infectious or pharmacologic factors) followed by neostigmine and decompressive colonoscopy. Surgery is reserved for patients with clinical deterioration or with evidence of colonic ischemia or perforation. A 60-year-old lady presented with fever, altered sensorium, obstipation, bradycardia and abdominal distension. Investigation revealed hyponatremia and acute colonic pseudo-obstruction. Supportive measures and decompressive colonoscopy were not of great benefit. Thyroid profile was suggestive of primary hypothyroidism. Colonic motility was restored only on starting thyroxin. The case is illustrative of the need to consider hypothyroidism, a common endocrine disorder, in the differential diagnosis of Ogilvie's.

Maternal colonization or infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae in Africa: A systematic review and meta-analysis.

PubMed

Bulabula, Andre N H; Dramowski, Angela; Mehtar, Shaheen

2017-11-01

To summarize published studies on the prevalence of and risk factors for maternal bacterial colonization and/or infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in pregnant and/or post-partum women in Africa. A systematic review was conducted using the PubMed, Scopus, and Google Scholar databases. Bibliographies of included eligible studies were manually searched to identify additional relevant articles. No language restriction was applied. The timeframe of the search included all records from electronic database inception to July 15, 2017. A random-effects meta-analysis was performed to summarize the prevalence and the 95% confidence intervals (CI) of ESBL-E colonization or infection in pregnant or post-partum women in Africa. The meta-analysis was conducted using STATA IC 13.1 software and the metaprop function/plugin. Ten studies (seven on pregnant women and three on post-partum women) were included, documenting a 17% prevalence of maternal colonization with ESBL-E in Africa (95% CI 10-23%). The prevalence of ESBL-E in community isolates exceeded that in isolates from the hospital setting (22% vs. 14%). The most frequently reported ESBL-encoding gene was CTX-M (cefotaxime hydrolyzing capabilities). Data on risk factors for maternal ESBL-E colonization and infection are very limited. The prevalence of colonization and/or infection with ESBL-E in pregnant and post-partum women in Africa exceeds that reported from high- and middle-income settings, representing a risk for subsequent neonatal colonization and/or infection with ESBL-E. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Radiographic findings and clinical factors in dogs with surgically confirmed or presumed colonic torsion.

PubMed

Gremillion, Christine L; Savage, Mason; Cohen, Eli B

2018-05-01

Colonic torsion is a life-threatening condition in dogs and radiographic findings for this condition have not been well described. The purpose of this retrospective case series was to describe radiographic findings and clinical signs in a group of dogs with colonic torsion. Inclusion criteria were dogs presenting during the period of 2006 and 2016, and that had abdominal radiography and a surgically confirmed or presumed diagnosis of colonic torsion. For each dog, clinical data were recorded from medical records and imaging findings were recorded from retrieved plain radiographs and positive contrast radiographs in which barium enema was performed. Fourteen dogs met inclusion criteria. Of these, nine dogs had colonic torsion confirmed at surgery, with five dogs having surgical confirmation of colonic congestion or mesenteric torsion. Radiographic findings included segmental distention of the colon (14/14), focal narrowing of the colon (11/14), displacement of cecum (11/14), displacement of descending colon (14/14), and mild to no small intestinal distention (14/14). In cases where barium enema was performed, focal narrowing of the colon and longitudinal striations that course in a helical pattern were identified, termed the "torsion sign." Vomiting was the most common clinical sign observed (12/14), followed by abdominal pain in a small majority of cases (8/14). Severe abdominal pain and hypovolemic shock were uncommon in the patients reported (3/14). Colonic torsion should be considered as a differential diagnosis for dogs with radiographic segmental colonic distention with displacement of the descending colon and cecum. Barium enema is recommended for more definitive diagnosis. © 2018 American College of Veterinary Radiology.

Immunologic Control of Diarrheal Disease Due to Enterotoxigenic Escherichia coli: Reactogenicity, Immunogenicity, and Efficacy Studies of Pili Vaccines

DTIC Science & Technology

1981-09-01

pathogens that lack CFA/I including enteropathogenic E. coli, some ETEC ana Vibrio cholerae (Figure 1). The mean change in net O.D. between the paired...intestine. In a further analogy, we have found that 20% of 50 recipients of a highly ad- hesive non-toxigenic Vibrio cholerae attenuated iaccine strain...and Characteristics of a Vibrio cholerae Mutant Lacking the A (ADP-Ribosylating) Portion of the Cholera Enterotoxin. Proc. Nat. Acad. Sci. USA 76:2052

Outboard Motor Maximizes Power and Dependability

NASA Technical Reports Server (NTRS)

2008-01-01

Developed by Jonathan Lee, a structural materials engineer at Marshall Space Flight Center, and PoShou Chen, a scientist with Huntsville, Alabama-based Morgan Research Corporation, MSFC-398 is a high-strength aluminum alloy able to operate at high temperatures. MSFC-398 was licensed for marine applications by Bombardier Recreational Products Inc., and is now found in the complete line of Evinrude E-TEC outboard motors, a line of two-stroke motors that maintain the power and dependability of a two-stroke with the refinement of a four-stroke.

Mechanics of Composite Materials with Different Moduli in Tension and Compression

DTIC Science & Technology

1978-07-01

100% and 400% for carbon-carbon. The principal objective DD N 73 1473 EDITION OF I NOV65 IS OBSOLETE UNCLASSIFIED i i SECURITY CLASSIFICATION OF THIS...corrected. 40 TABLE 2.3 BUCKLING OF PAYLOAD BAY DOOR PANELS WITH VARIOUS LIGHTNING STRIKE PROTECTION CONCEPTS BUCKLING LOAD, N ., lb/in. CONFIGURATION...ORTHOTROPY AND HIGH Et/Ec p 70 P CC"’ CHANGE C02 CHAC -l- AXIAL CHANGE COMMISSION INTIIUNAL IXTERNAL i peamal PRESSURE 40 60 s AXIAL 0 IAN C. TENMiON

Relationship of some biosocial factors to colon cancer in Belgrade (Yugoslavia).

PubMed

Vlajinac, H; Jarebinski, M; Adanja, B

1987-01-01

Eighty-eight patients with histologically confirmed colon cancer and two control groups individually matched by age, sex and place of residence, were interviewed about demographic, biosocial and medical variables. The use of laxatives, past history of large bowel disease and coffee consumption for 20 or more years were significantly more frequent among colon cancer than in their controls. No significant differences were found between cases and controls with respect to education level, job activity, smoking habits, alcohol consumption and cholecystectomy.

[Systemic candidiasis in medical intensive care unit: analysis of risk factors and the contribution of colonization index].

PubMed

Massou, S; Ahid, S; Azendour, H; Bensghir, M; Mounir, K; Iken, M; Lmimouni, B E; Balkhi, H; Drissi Kamili, N; Haimeur, C

2013-06-01

Description of the epidemiological and clinical characteristics of the patients introducing risk factors of invasive candidiasis. Analysis of risk factors for candidiasis invasive and evaluation of the contribution of colonization index (CI) in the diagnosis of the systematic candidiasis in medical intensive care. Prospective observational study (October 2007 to October 2009). The selected patients present risk factors of system IC candidiasis with an infectious syndrome or clinical signs suggestive of Candida infection and hospitalized more than 48 hours in medical intensive care unit. Pittet's colonization index was calculated at admission and then once a week added to a blood culture. Patients were classified according to level of evidence of Candida infection and the degree of colonization (CI<0.5, CI ≥ 0.5). The study included 100 patients. Mean age of our patients was 55.8 ± 18.2 years with male prevalence. Neurological disease was the most frequent pathology in admission (48%). The most common risk factors were broad-spectrum antibiotics and foreign material. In the various mycology IC specimens, Candida albicans was the most frequent, followed by C. tropicalis, then C. glabrata. The CI was greater than or equal to 0.5 at 53% of the patients, and less than 0.5 in 47% of the cases. Among the patients, 15% developed an invasive candidiasis. In multivariate analysis, the corticosteroid therapy was associated with a high colonisation (IC ≥ 0.5) and neutropenia with a high risk of systemic candidiasis. The positive predictive value of CI was 26%. The negative predictive value was 98%, the sensitivity and specificity was 93% and 48% respectively. CI has the advantage to provide a quantified data of the patient's situation in relation to the colonization. But, it isn't helpful with patients having an invasive candidiasis in medical intensive care unit. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Candida tropicalis in a Neonatal Intensive Care Unit: Epidemiologic and Molecular Analysis of an Outbreak of Infection with an Uncommon Neonatal Pathogen

PubMed Central

Roilides, Emmanuel; Farmaki, Evangelia; Evdoridou, Joanna; Francesconi, Andrea; Kasai, Miki; Filioti, Joanna; Tsivitanidou, Maria; Sofianou, Danai; Kremenopoulos, George; Walsh, Thomas J.

2003-01-01

From June to July 1998, two episodes of Candida tropicalis fungemia occurred in the Aristotle University neonatal intensive care unit (ICU). To investigate this uncommon event, a prospective study of fungal colonization and infection was conducted. From December 1998 to December 1999, surveillance cultures of the oral cavities and perinea of the 593 of the 781 neonates admitted to the neonatal ICU who were expected to stay for >7 days were performed. Potential environmental reservoirs and possible risk factors for acquisition of C. tropicalis were searched for. Molecular epidemiologic studies by two methods of restriction fragment length polymorphism analysis and two methods of random amplified polymorphic DNA analysis were performed. Seventy-two neonates were colonized by yeasts (12.1%), of which 30 were colonized by Candida albicans, 17 were colonized by C. tropicalis, and 5 were colonized by Candida parapsilosis. From December 1998 to December 1999, 10 cases of fungemia occurred; 6 were due to C. parapsilosis, 2 were due to C. tropicalis, 1 was due to Candida glabrata, and 1 was due to Trichosporon asahii (12.8/1,000 admissions). Fungemia occurred more frequently in colonized than in noncolonized neonates (P < 0.0001). Genetic analysis of 11 colonization isolates and the two late blood isolates of C. tropicalis demonstrated two genotypes. One blood isolate and nine colonization isolates belonged to a single type. The fungemia/colonization ratio of C. parapsilosis (3/5) was greater than that of C. tropicalis (2/17, P = 0.05), other non-C. albicans Candida spp. (1/11, P = 0.02), or C. albicans (0/27, P = 0.05). Extensive environmental cultures revealed no common source of C. tropicalis or C. parapsilosis. There was neither prophylactic use of azoles nor other risk factors found for acquisition of C. tropicalis except for total parenteral nutrition. A substantial risk of colonization by non-C. albicans Candida spp. in the neonatal ICU may lead to a preponderance of C. tropicalis as a significant cause of neonatal fungemia. PMID:12574275

Genetic mapping of secretion and functional determinants of the Vibrio cholerae TcpF colonization factor.

PubMed

Krebs, Shelly J; Kirn, Thomas J; Taylor, Ronald K

2009-06-01

Colonization of the human small intestine by Vibrio cholerae requires the type IV toxin-coregulated pilus (TCP). TcpF, which is encoded within the tcp operon, is secreted from the bacterial cell by the TCP apparatus and is also essential for colonization. Bacteria lacking tcpF are deficient in colonization, and anti-TcpF antibodies are protective in the infant mouse cholera model. In order to elucidate the regions of the protein that are required for secretion through the TCP apparatus and for its function in colonization, random mutagenesis of tcpF was performed. Analysis of these mutants suggests that multiple regions throughout the protein influence extracellular secretion and that determinants near the C terminus are important for the function of TcpF in colonization. The TcpF proteins of certain environmental V. cholerae isolates with 31% to 66% identity to pathogenic V. cholerae TcpF showed higher similarity in regions identified as secretion determinants but diverged in regions found to be important for colonization. These environmental TcpF proteins are secreted from the pathogenic strain; however, they do not mediate colonization in the infant mouse model. Here we provide genetic evidence pointing toward regions of TcpF that influence secretion, as well as regions that play an important role in in vivo colonization.

Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis

PubMed Central

Chan, Grace J.; Lee, Anne CC; Baqui, Abdullah H.; Tan, Jingwen; Black, Robert E.

2013-01-01

Background Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period. Methods and Findings We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors. Conclusions Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis. Please see later in the article for the Editors' Summary PMID:23976885

Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis.

PubMed

Gavert, Nancy; Sheffer, Michal; Raveh, Shani; Spaderna, Simone; Shtutman, Michael; Brabletz, Thomas; Barany, Francis; Paty, Phillip; Notterman, Daniel; Domany, Eytan; Ben-Ze'ev, Avri

2007-08-15

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of beta-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy.

Colonic Saturated Fatty Acid Concentrations and Expression of COX-1, but not Diet, Predict Prostaglandin E2 in Normal Human Colon Tissue.

PubMed

Sidahmed, ElKhansa; Sen, Ananda; Ren, Jianwei; Patel, Arsh; Turgeon, D Kim; Ruffin, Mack T; Brenner, Dean E; Djuric, Zora

2016-10-01

Prostaglandin E2 (PGE2) in the colon is a pro-inflammatory mediator that is associated with increased risk of colon cancer. In this study, expression of genes in the PGE2 pathway were quantified in colon biopsies from a trial of a Mediterranean versus a Healthy Eating diet in 113 individuals at high risk for colon cancer. Colon biopsies were obtained before and after 6 months of intervention. Quantitative, real-time PCR was used to measure mRNA expression of prostaglandin H synthases (PTGS1 and 2), prostaglandin E synthases (PTGES1 and 3), prostaglandin dehydrogenase (HPGD), and PGE2 receptors (PTGER2, PTGER4). The most highly expressed genes were HPGD and PTGS1. In multivariate linear regression models of baseline data, both colon saturated fatty acid concentrations and PTGS1 expression were significant, positive predictors of colon PGE2 concentrations after controlling for nonsteroidal anti-inflammatory drug use, gender, age, and smoking status. The effects of dietary intervention on gene expression were minimal with small increases in expression noted for PTGES3 in both arms and in PTGER4 in the Mediterranean arm. These results indicate that short-term dietary change had little effect on enzymes in the prostaglandin pathway in the colon and other factors, such as differences in fatty acid metabolism, might be more influential.