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Sample records for resistant mice strains

  1. Genetic basis of resistance to trauma in inbred strains of mice

    SciTech Connect

    Radojicic, C.; Andric, B.; Simovic, M.; Dujic, A.; Marinkovic, D. )

    1990-02-01

    In this study the resistance to mechanical, thermal, and radiation trauma in four inbred strains of mice (AKR, BALB/c, CBA, and C57Bl/6) was compared with the degree of genetic resemblance, by analyzing the allozyme variabilities of these strains. It was shown that the highest degree of genetic resemblance was among CBA and AKR strains, which correlated with a similar degree of resistance to trauma. On the other hand, BALB/c and C57Bl/6 strains expressed significant differences, both genetically and with respect to the responses to trauma. The hypothesis is introduced that the genetic determination of the resistance to trauma is based on: (a) a polygenic control of general physiological homeostasis, with the possibility that (b) some specific genes or single loci may contribute more than others to such adaptations of the strains tested.

  2. Age-Dependent Resistance to Excitotoxicity in Htt CAG140 Mice and the Effect of Strain Background

    PubMed Central

    Strong, Melissa K.; Southwell, Amber L.; Yonan, Jennifer M.; Hayden, Michael R.; MacGregor, Grant R.; Thompson, Leslie M.; Steward, Oswald

    2013-01-01

    Mouse strain background can influence vulnerability to excitotoxic neuronal cell death and potentially modulate phenotypes in transgenic mouse models of human disease. Evidence supports a contribution of excitotoxicity to the selective death of medium spiny neurons in Huntington’s disease (HD). Here, we assess whether strain differences in excitotoxic vulnerability influence striatal cell death in a knock-in mouse model of HD. Previous studies that evaluated resistance to excitotoxic lesions in several mouse models of HD had variable outcomes. In the present study, we directly compare one model on two different background strains to test the contribution of strain to excitotoxicity-mediated neurodegeneration. Mice of the FVB/N strain, which are highly vulnerable to excitotoxicity, become extremely resistant to quinolinic acid-induced striatal neurodegeneration with age, when carrying a huntingtin (Htt) allele expressing a HD transgene (CAG140). The resistance is much greater than the age-dependent resistance that has been previously reported in YAC128 mice. By 12 months of age, both heterozygous and homozygous FVB.CAG140 mice displayed virtually complete resistance to quinolinic acid-induced striatal neurodegeneration. A similar resistance develops in CAG140 mice on a C57BL/6N background although the effect size is smaller because C57BL/6N mice are already resistant due to genetic background. In a direct comparison with the YAC128 mice, FVB.CAG140 mice have greater resistance. FVB.CAG140 mice are also resistant to neurodegeneration following kainic acid-induced status epilepticus suggesting the existence of a common cellular mechanism that provides protection against multiple types of excitotoxic insult. These findings establish FVB.CAG140 mice as a useful model to investigate the cellular and molecular mechanisms that confer neuroprotection against excitotoxicity. PMID:23833693

  3. Intact immune defenses are required for mice to resist the ts-4 vaccine strain of Toxoplasma gondii.

    PubMed Central

    Sayles, P C; Johnson, L L

    1996-01-01

    The ts-4 strain of Toxoplasma gondii is a temperature-sensitive mutant that fails to grow at 40 degrees C in vitro. Unlike mildly virulent cyst-forming strains, which can cause fatal chronic infections in certain mouse strains, ts-4 has been widely used to vaccinate mice against virulent T. gondii and is a valuable tool with which to investigate mechanisms of acquired resistance to this parasite. In this report, the basis for the avirulence of ts-4 is analyzed. It is shown that ts-4 is able to persist long-term in vivo in mildly immunocompromised mice, which rules out an intrinsic growth defect as a reason for avirulence. ts-4 does not induce body temperatures in mice as high as that needed to kill it in vitro. Moreover, the mild fevers elicited in resistant B6 mice are also seen in susceptible C57BL/6 scid/scid mice. However, ts-4 elicits strong preimmune defenses, dependent on gamma interferon, which are needed by mice to survive acute infection. Furthermore, CD4+ and CD8+ T-cell-dependent acquired immunity is essential for long-term survival of ts-4-infected mice. PMID:8757838

  4. Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth.

    PubMed Central

    Fallon, M T; Benjamin, W H; Schoeb, T R; Briles, D E

    1991-01-01

    We have previously shown that intranasal infection of mice with mouse hepatitis virus (MHV) strain UAB (MHV-UAB) increases their resistance to Salmonella typhimurium injected intravenously 6 days later. To study how salmonella resistance was induced, BALB/cAnNCr mice were infected with salmonella strains carrying specific genetic alterations. One set of studies compared the effect of MHV infection on subsequent salmonella infections with AroA- (avirulent) and Aro+ (virulent) salmonellae. Unlike its effect on Aro+ salmonellae, MHV failed to reduce the number of AroA- salmonellae recovered from mice. Because AroA- S. typhimurium shows almost no growth in vivo, this failure indicated that the effect of MHV on salmonella resistance required growth of the infecting salmonellae. In other studies, the effect of MHV infection on both growth and killing were monitored simultaneously in mice with growing salmonellae carrying a single copy of the temperature-sensitive pHSG422 plasmid, which is unable to replicate in vivo. MHV infection reduced salmonella growth but caused no increase in salmonella killing. MHV infection of mice given wild-type salmonellae also resulted in no increase in salmonella killing 4 h after salmonella challenge. These studies demonstrate that MHV-UAB infection increases host resistance to salmonellae by enhancing suppression of bacterial growth instead of by increasing the amount of salmonella killing. PMID:1847697

  5. Assessment of combination therapy in BALB/c mice injected with carbapenem-resistant Enterobacteriaceae strains

    PubMed Central

    Salloum, Noor A.; Kissoyan, Kohar Annie B.; Fadlallah, Sukayna; Cheaito, Katia; Araj, George F.; Wakim, Rima; Kanj, Souha; Kanafani, Zeina; Dbaibo, Ghassan; Matar, Ghassan M.

    2015-01-01

    Monotherapeutic options for carbapenem resistant infections are limited. Studies suggest that combination therapy may be associated with better outcomes than monotherapies. However, this is still controversial. This study assessed, the efficacy of combination therapy against carbapenem resistant Enterobacteriaceae harboring singly various extended spectrum beta lactamase or carbapenemase encoding genes. Thus, four isolates harboring either blaCTXM-15, blaCTXM-15 and blaOXA-48, blaNDM-1, or blaKPC-2 genes were selected for testing. Minimal inhibitory concentration was determined by broth dilution method. Gene transcript levels on single and combined treatments were done in vitro and in vivo by qRT-PCR. Assessment of treatments was done in BALB/c mice according to a specific protocol. As such, the qRT-PCR revealed a significant decrease of transcript levels in all isolates upon using rifampicin or tigecycline, singly or in combination with colistin. However, variable levels were obtained using colistin singly or in combination with meropenem or fosfomycin. In vivo assessment showed that all combinations used were effective against isolates harboring blaCTXM-15, blaOXA-48, and blaNDM-1. Conversely, the most significant combination against the isolate harboring blaKPC-2 gene was colistin with either carbapenem, fosfomycin, or kanamycin. As a conclusion, combination therapy selected based on the type of carbapenemase produced, appeared to be non-toxic and might be effective in BALB/c mice. Therefore, the use of a rationally optimized combination therapy might lead to better results than monotherapy, however, clinical trials are needed for human consumption. PMID:26441926

  6. Assessment of combination therapy in BALB/c mice injected with carbapenem-resistant Enterobacteriaceae strains.

    PubMed

    Salloum, Noor A; Kissoyan, Kohar Annie B; Fadlallah, Sukayna; Cheaito, Katia; Araj, George F; Wakim, Rima; Kanj, Souha; Kanafani, Zeina; Dbaibo, Ghassan; Matar, Ghassan M

    2015-01-01

    Monotherapeutic options for carbapenem resistant infections are limited. Studies suggest that combination therapy may be associated with better outcomes than monotherapies. However, this is still controversial. This study assessed, the efficacy of combination therapy against carbapenem resistant Enterobacteriaceae harboring singly various extended spectrum beta lactamase or carbapenemase encoding genes. Thus, four isolates harboring either bla CTXM-15, bla CTXM-15 and bla OXA-48, bla NDM-1, or bla KPC-2 genes were selected for testing. Minimal inhibitory concentration was determined by broth dilution method. Gene transcript levels on single and combined treatments were done in vitro and in vivo by qRT-PCR. Assessment of treatments was done in BALB/c mice according to a specific protocol. As such, the qRT-PCR revealed a significant decrease of transcript levels in all isolates upon using rifampicin or tigecycline, singly or in combination with colistin. However, variable levels were obtained using colistin singly or in combination with meropenem or fosfomycin. In vivo assessment showed that all combinations used were effective against isolates harboring bla CTXM-15, bla OXA-48, and bla NDM-1. Conversely, the most significant combination against the isolate harboring bla KPC-2 gene was colistin with either carbapenem, fosfomycin, or kanamycin. As a conclusion, combination therapy selected based on the type of carbapenemase produced, appeared to be non-toxic and might be effective in BALB/c mice. Therefore, the use of a rationally optimized combination therapy might lead to better results than monotherapy, however, clinical trials are needed for human consumption. PMID:26441926

  7. Complete mitochondrial genome sequence and mutations of the insulin resistance model inbred C57BL/6 mice strain.

    PubMed

    Meng, Xiao-Mei; Tang, Yu-Xiao; Wang, Ji-Chang; Dong, Yao-Zhong

    2016-05-01

    In the present work we undertook the complete mitochondrial genome sequencing of an important insulin resistance model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported. PMID:25350740

  8. Genetic analysis of resistance to Type-1 Diabetes in ALR/Lt mice, a NOD-related strain with defenses against autoimmune-mediated diabetogenic stress.

    PubMed

    Mathews, Clayton E; Graser, Robert T; Bagley, Rebecca J; Caldwell, Jason W; Li, Renhua; Churchill, Gary A; Serreze, David V; Leiter, Edward H

    2003-10-01

    ALR mice are closely related to type-1 diabetes mellitus (T1DM)-prone NOD mice. The ALR genome confers systemically elevated free radical defenses, dominantly protecting their pancreatic islets from free radical generating toxins, cytotoxic cytokines, and diabetogenic T cells. The ALR major histocompatibility complex (MHC) ( H2(gx) haplotype) is largely, but not completely identical with the NOD H2(g7) haplotype, sharing alleles from H2-K through the class II and distally into the class III region. This same H2(gx) haplotype in the related CTS strain was linked to the Idd16 resistance locus. In the present study, ALR was outcrossed to NOD to fine map the Idd16 locus and establish chromosomal regions carrying other ALR non-MHC-linked resistance loci. To this end, 120 (NODxALR)xNOD backcross progeny females were monitored for T1DM and genetic linkage analysis was performed on all progeny using 88 markers covering all chromosomes. Glucosuria or end-stage insulitis developed in 32 females, while 88 remained both aglucosuria and insulitis free. Three ALR-derived resistance loci segregated. As expected, one mapped to Chromosome 17, with peak linkage mapping just proximal to H2-K. A novel resistance locus mapped to Chr 8. A pairwise scan for interactions detected a significant interaction between the loci on Chr 8 and Chr 17. On Chr 3, resistance segregated with a marker between previously described Idd loci and coinciding with an independently mapped locus conferring a suppressed superoxide burst by ALR neutrophils (Susp). These results indicate that the Idd16 resistance allele, defined originally by linkage to the H2(gx) haplotype of CTS, is immediately proximal to H2-K. Two additional ALR-contributed resistance loci may be ALR-specific and contribute to this strain's ability to dissipate free-radical stress. PMID:14513297

  9. Early phase pharmacokinetics and pulmonary disposition of parenteral bleomycin A2 (BLM A2) in BLM sensitive and resistant strains of mice

    SciTech Connect

    Harrison, J.H.; Filderman, A.E.; Lazo, J.S.

    1986-03-01

    Recent studies have shown that C57BL/6N mice are more sensitive than BALB/c mice to the pulmonary fibrotic effects of BLM. To determine whether the two strains show corresponding differences in BLM pharmacokinetics and pulmonary disposition after parenteral injection, the authors treated C57BL/6N and BALB/c mice with a single dose of (/sup 3/H)-BLM (80 mg/kg,iv). Serial blood samples were collected over 30 min from each animal, followed by pulmonary lavage and collection organs. In C57 BL/6N mice, BLM A2 plasma levels were maximal (178-227 ..mu..g/ml) in the first sample (2 min) and declined in a first order manner with a half-life of 12.6 +/- 3.6 (SD) min. The Vd was 232 +/- 29 ml/kg body weight. Pulmonary lavage recovered 68.1 +/- 3.5% of total lung radioactivity. BLM A2 was the predominant radioactive species and was present in equal proportions in lavage fluid and lung tissue. BALB/c mice showed similar BLM A2 distribution and elimination, and the recovery of BLM A2 in lavage fluid was not decreased as compared with C57BL/6N mice. Therefore, the resistance of BALB/c mice to BLM pulmonary toxicity does not appear to result from enhanced elimination of the drug or relative exclusion of BLM from lung tissues at this dose. These findings indicate that after iv injection, BLM rapidly distributes through a volume similar to extracellular water and, of particular interest, the majority of lung BLM is accessible to pulmonary lavage.

  10. Dynamics of the intracerebral and splenic cytokine mRNA production in Toxoplasma gondii-resistant and -susceptible congenic strains of mice.

    PubMed Central

    Deckert-Schlüter, M; Albrecht, S; Hof, H; Wiestler, O D; Schlüter, D

    1995-01-01

    Oral infection with a low-virulence strain of Toxoplasma gondii (Tg) induced a persisting encephalitis in resistant strains of mice. In the present study we have examined transcripts of various cytokines during acute and chronic stages of murine Tg encephalitis. In the brain of infected animals, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-6, IL-10 and IL-12 mRNA were induced to a significant extent, but only low levels of IL-4 mRNA were detectable. A similar cytokine profile was observed in the spleen. However, in contrast to the brain, the increase of IL-2 mRNA was particularly pronounced in the spleen, whereas the opposite was found for IFN-gamma and TNF-alpha mRNA. Thus, cytokines involved in T-cell proliferation were more prevalent in the spleen, but in the brain, where Tg actively multiplies, the effector molecules IFN-gamma and TNF-alpha were preferentially up-regulated. In addition, a detailed analysis of cytokine mRNA levels in major histocompatibility complex (MHC)-congenic strains of BALB and B10 mice revealed that the genetically regulated susceptibility to Tg was correlated with the amount of intracerebrally produced cytokine mRNA for IFN-gamma, TNF-alpha and IL-6. Mice with a strong increase of these cytokine mRNA were significantly better protected against Tg. This indicates that the outcome of toxoplasmosis may be critically dependent on an adequately regulated intracerebral immune response. Images Figure 1 Figure 2 Figure 3 PMID:7558129

  11. Innate resistance of mice to experimental infection with Naegleria fowleri.

    PubMed Central

    Haggerty, R M; John, D T

    1978-01-01

    The mouse system provides an excellent model for studying host resistance to Naegleria fowleri, the agent of primary amoebic meningoencephalitis. Innate resistance to infection with N. fowleri was examined with respect to infecting dose and the age, sex, and strain of mice. Intravenous inoculation with 10(7) amoebae per mouse produced 100% mortality in 9 days, whereas inoculation with fewer amoebae reduced the cumulative mortality. Male and female DUB/ICR mice of varying ages were inoculated intravenously with 2.5 X 10(5) N. fowleri per g of body weight. The youngest mice died first, with 100% mortality for both males and females, and mortality decreased with increasing age. Female mice were significantly more resistant to infection than males. Five strains of mice weighing approximately 20 g were inoculated intravenously with weight-adjusted doses; mortality ranged from 10% in C57BL/6 mice to 95% in A/HeCr mice. PMID:669800

  12. Human prion strain selection in transgenic mice

    PubMed Central

    Giles, Kurt; Glidden, David V.; Patel, Smita; Korth, Carsten; Groth, Darlene; Lemus, Azucena; DeArmond, Stephen J.; Prusiner, Stanley B.

    2010-01-01

    Transgenic (Tg) mice expressing chimeras of mouse and human prion proteins (PrP) have shorter incubation periods for Creutzfeldt-Jakob disease (CJD) prions than mice expressing full-length human PrP. Increasing the sequence similarity of the chimeric PrP to mouse PrP, by reverting human residues to mouse, resulted in a Tg line, denoted Tg22372, which was susceptible to sporadic (s) CJD prions in ~110 days 1. Reversion of one additional residue (M111V) resulted in a new Tg line, termed Tg1014, susceptible to sCJD prions in ~75 days. Tg1014 mice also has shorter incubation periods for variant (v) CJD prions, providing a more tractable model for studying this prion strain. Transmission of vCJD prions to Tg1014 mice resulted in two different strains, determined by neuropathology and biochemical analysis, which correlated with the length of the incubation time. One strain had the biochemical, neuropathological, and transmission characteristics including longer incubation times of the inoculated vCJD strain; the second strain produced a phenotype resembling that of sCJD prions including relatively shorter incubation periods. Mice with intermediate incubation periods for vCJD prions had a mixture of the two strains. Both strains were serially transmitted in Tg1014 mice, which led to further reduction in incubation periods. Conversion of vCJD-like to sCJD-like strains was favored in Tg1014 mice more than in the Tg22372 line. The single amino acid difference therefore appears to offer selective pressure for propagation of the sCJD-like strain. These two Tg mouse lines provide relatively rapid models to study human prion diseases as well as the evolution of human prion strains. PMID:20695008

  13. Virulence of 32 Salmonella Strains in Mice

    PubMed Central

    Swearingen, Matthew C.; Porwollik, Steffen; Desai, Prerak T.; McClelland, Michael; Ahmer, Brian M. M.

    2012-01-01

    Virulence and persistence in the BALB/c mouse gut was tested for 32 strains of Salmonella enterica for which genome sequencing is complete or underway, including 17 serovars within subspecies I (enterica), and two representatives of each of the other five subspecies. Only serovar Paratyphi C strain BAA1715 and serovar Typhimurium strain 14028 were fully virulent in mice. Three divergent atypical Enteritidis strains were not virulent in BALB/c, but two efficiently persisted. Most of the other strains in all six subspecies persisted in the mouse intestinal tract for several weeks in multiple repeat experiments although the frequency and level of persistence varied considerably. Strains with heavily degraded genomes persisted very poorly, if at all. None of the strains tested provided immunity to Typhimurium infection. These data greatly expand on the known significant strain-to-strain variation in mouse virulence and highlight the need for comparative genomic and phenotypic studies. PMID:22558320

  14. Vaccination of adult and newborn mice of a resistant strain (C57BL/6J) against challenge with leukemias induced by Moloney murine leukemia virus

    SciTech Connect

    Reif, A.E.

    1985-01-01

    Adult or newborn C57BL/6J mice were immunized with isogenic Moloney strain MuLV-induced leukemia cells irradiated with 10,000 rads or treated with low concentrations of formalin. Groups of immunized and control mice were challenged with a range of doses of viable leukemia cells, and tumor deaths were recorded for 90 days after challenge. Then, the doses of challenge cells which produced 50% tumor deaths were calculated for immunized and control mice. The logarithm of their ratio quantified the degree of protection provided by immunization. For adult C57BL/6J mice, a single immunization with MuLV-induced leukemia cells was not effective; either cells plus Bacillus Calmette-Guerin or Corynebacterium parvum, or else two immunizations with irradiated leukemia cells were needed to produce statistically significant increases in the values of the doses of challenge cells which produced 50% tumor deaths. Cross-protection was obtained by immunization with other isogenic MuLV-induced leukemias, but not by immunization with isogenic carcinogen-induced tumors or with an isogenic spontaneous leukemia. For newborn mice, a single injection of irradiated leukemia cells provided 1.3 to 1.5 logs of protection, and admixture of B. Calmette-Guerin or C. parvum increased this protection to 2.4 to 2.7 logs. Since irradiated and frozen-thawed MuLV-induced leukemia cells contained viable MuLV, leukemia cells treated with 0.5 or 1.0% formalin were tested as an alternative. A single injection of formalin-treated isogenic leukemia cells admixed with C. parvum provided between 1.7 and 2.8 logs of protection. These results demonstrate that a single vaccination of newborn animals against a highly antigenic virally induced leukemia produces strong protection against a subsequent challenge with viable leukemia cells.

  15. A highly acid-resistant novel strain of Lactobacillus johnsonii No. 1088 has antibacterial activity, including that against Helicobacter pylori, and inhibits gastrin-mediated acid production in mice

    PubMed Central

    Aiba, Yuji; Nakano, Yasuhiro; Koga, Yasuhiro; Takahashi, Kenji; Komatsu, Yasuhiko

    2015-01-01

    A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric juice of a healthy Japanese male volunteer, and characterized for its effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was found to have the strongest acid resistance among several lactobacilli examined (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance property was a specific characteristic of this strain of L. johnsonii. When cultured with various virulent bacteria, L. johnsonii No. 1088 inhibited the growth of Helicobacter pylori,Escherichia coli O-157, Salmonella Typhimurium, and Clostridium difficile, in which case its effectiveness was more potent than that of a type strain of L. johnsonii,JCM2012. In addition to its effect in vitro, L. johnsonii No. 1088 inhibited the growth of H. pylori in human intestinal microbiota-associated mice in both its live and lyophilized forms. Moreover, L. johnsonii No. 1088 suppressed gastric acid secretion in mice via decreasing the number of gastrin-positive cells in the stomach. These results taken together suggest that L. johnsonii No. 1088 is a unique lactobacillus having properties beneficial for supporting H. pylori eradication by triple therapy including the use of a proton pump inhibitor (PPI) and also for prophylaxis of gastroesophageal reflux disease possibly caused after H. pylori eradication as a side effect of PPI. PMID:25771812

  16. Tympanometry Assessment of 61 Inbred Strains of Mice

    PubMed Central

    Zheng, Qing Yin; Tong, Yi-Cai Isaac; Alagramam, Kumar N.; Yu, Heping

    2007-01-01

    Otitis Media (OM) accounts for more than 20 million clinic visits in the United States every year. Resistance to antibiotics has hampered current management of the disease. Identification of genetic factors underlying susceptibility to OM is greatly needed in order to develop alternative treatment strategies. Genetically defined inbred mouse strains offer a powerful tool for dissecting genetic and environmental factors that may lead to OM in mice. Here we report a study of middle ear function of 61 genetically diverse inbred strains of mice using tympanometry. Of the 61 inbred strains tested, the 129P1/ReJ, 129P3/J, 129S1/SvImJ, 129X1/SvJ, A/HeJ, BALB/cJ, BUB/BnJ, C57L/J, EL/SuzSeyFrkJ, FVB/NJ, I/LnJ, LP/J, NZB/BlNJ, PL/J and YBR/Ei strains exhibited tympanograms that were statistically different from other healthy strains according to parameters including middle ear pressure, volume and compliance. These differences are most likely the result of genetic factors that, when understood, will facilitate prevention and treatment of otitis media in humans. In addition, a negative correlation between age and compliance of the tympanic membrane was discovered. This is the first report to successfully use tympanometry to measure mouse middle ear function, which has been a challenge for the hearing research field because of the mouse’s tiny ear size. PMID:17611057

  17. Attenuation and Production of the Amphotericin B-Resistant Leishmania tropica Strain

    PubMed Central

    Khan, Imran; Khan, Momin; Umar, Muhammad Naveed; Oh, Deog-Hwan

    2016-01-01

    Background Infections caused by Leishmania are becoming major public health problems on a global scale. Many species of Leishmania around the world are obtaining resistance levels of up to 15 folds, as estimated by the World Health Organization. Leishmania showing resistance is relatively difficult to observe and maintain in laboratory settings. Objectives The current study deals with the generation of Leishmania tropica strains that are resistant to amphotericin B (amp B). Materials and Methods The L. tropica strain was attenuated using continuous passaging 20 times. The infectivity of L. tropica was confirmed in BALB/c mice. The L. tropica resistant strain was produced in vitro using a continuous increase in drug pressure. The cross resistance of L. tropica to other drugs was also investigated. Results After 20 continuous passages, the BALB/c mice tested negative in the development of leishmaniasis. At a concentration of 0.1 µg/mL, L. tropica showed resistance to amp B. The newly developed promastigotes were 16 times more resistant compared to the resistance of the wild type promastigotes. The resistant L. tropica strain showed cross resistance to itraconazole and had a resistance index that was greater than five. The resistant strain displayed maximum stability for more than three months in the drug-free medium. Conclusions The resistant strain of L. tropica can be produced in laboratories using continuous drug pressure. The attenuated resistant strain has significant implications (both medically and academically) in the ability to overcome resistance.

  18. High-Temperature Resistance Strain Gauges

    NASA Technical Reports Server (NTRS)

    Lei, Jih-Fen

    1994-01-01

    Resistance strain gauges developed for use at high temperatures in demanding applications like testing aircraft engines and structures. Measures static strains at temperatures up to 800 degrees C. Small and highly reproducible. Readings corrected for temperature within small tolerances, provided temperatures measured simultaneously by thermocouples or other suitable devices. Connected in wheatstone bridge.

  19. High temperature strain measurement with a resistance strain gage

    NASA Technical Reports Server (NTRS)

    Lei, Jih-Fen; Fichtel, ED; Mcdaniel, Amos

    1993-01-01

    A PdCr based electrical resistance strain gage was demonstrated in the laboratory to be a viable sensor candidate for static strain measurement at high temperatures. However, difficulties were encountered while transferring the sensor to field applications. This paper is therefore prepared for recognition and resolution of the problems likely to be encountered with PdCr strain gages in field applications. Errors caused by the measurement system, installation technique and lead wire attachment are discussed. The limitations and some considerations related to the temperature compensation technique used for this gage are also addressed.

  20. Host resistance to intranasal Acinetobacter baumannii reinfection in mice.

    PubMed

    Qiu, Hongyu; Li, Zack; KuoLee, Rhonda; Harris, Greg; Gao, Xiaoling; Yan, Hongbin; Xu, H Howard; Chen, Wangxue

    2016-07-01

    Acinetobacter baumannii is a major causative agent of healthcare-associated infection and develops multidrug resistance rapidly. However, little is known in the host defense mechanisms against this infection. In this study, we examined if mice recovered from a previous intranasal A. baumannii infection (recovered mice) are fully protected against a subsequent reinfection. We found that, despite the presence of specific serum IgG and mucosal IgA responses prior to the reinfection, the recovered mice were only marginally better protected against intranasal challenge with low doses of homologous or heterologous A. baumannii strains than the naïve mice. Post-challenge immune and inflammatory (cells and cytokines) responses were generally comparable between recovered and naïve mice although the recovered mice produced significantly higher amounts of IFN-γ and IL-17 and had higher percentages and numbers of resident lung CD44(hi)CD62L(-)CD4(+) and CD19(+) B lymphocytes. Taken together, our results suggest that mice recovered from a previous A. baumannii infection remain susceptible to reinfection, indicating the complexity of immune protection mechanism for this Gram-negative, multidrug-resistant emerging pathogen. PMID:27194730

  1. Dectin-1 is required for resistance to coccidioidomycosis in mice.

    PubMed

    Viriyakosol, Suganya; Jimenez, Maria del Pilar; Gurney, Michael A; Ashbaugh, Mark E; Fierer, Joshua

    2013-01-01

    We assessed the role of Dectin-1 in the immune response to the pathogenic fungus Coccidioides, both in vitro and in vivo, using mice with a targeted mutation in Clec7a. Elicited peritoneal macrophages responded to formalin-killed spherules (FKS) and alkali-treated FKS by secreting proinflammatory cytokines in a Dectin-1- and β-glucan-dependent manner. The responses of bone marrow-derived dendritic cells (BMDC) to the same stimulants were more complex; interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) secretion was independent of Dectin-1, while IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were largely but not entirely dependent on Dectin-1. After intranasal infection, Dectin-1(-/-) mice had lower concentrations of IL-12p70, gamma interferon (IFN-γ), IL-1β, and the Th17 cytokines IL-22, IL-23, and 17A in the lung lavage fluid, which may explain why they were significantly more susceptible to pulmonary coccidioidomycosis two weeks after infection. The Dectin-1 mutation was even more deleterious in (B6 × DBA/2)F(2) mice, which are more resistant to coccidioidomycosis than B6 mice by virtue of protective genes from DBA/2, a genetically resistant strain. We also found that two susceptible strains of mice (B6 and BALB/c) expressed much less Dectin-1 in their lungs than did resistant DBA/2 mice. We conclude that Dectin-1 is necessary for resistance to Coccidioides immitis, that Dectin-1 promotes both Th1 and Th17 protective immune responses to this infection, and that there is a correlation between expression of Dectin-1 by the inflammatory infiltrate and resistance to coccidioidomycosis. IMPORTANCE Coccidioidomycosis is a fungal infection endemic in the southwestern United States and neighboring Mexico, causing ~150,000 lung infections in people and resulting in ~17,000 hospitalizations annually in California alone. Very little is known about innate immunity to this fungus. This paper shows that Dectin-1, the primary

  2. Cerium-144-induced lung gumors in two strains of mice

    SciTech Connect

    Hahn, F.F.; Griffith, W.C.

    1995-12-01

    A major problem in the extrapolation of radiation cancer risk factors from one species or population to another is the choice of the risk model to use, either absolute or relative. The purpose of this study was to compare absolute and relative risk models in predicting the lung-tumor risks between a low lung-tumor incidence strain of mice and a high-incidence strain of mice. The conclusion from this study is that absolute risk is more accurate than relative risk for predicting lung tumor risk from high to low lung-tumor incidence strains of mice.

  3. Murine leukemia virus in organs of senescence-prone and -resistant mouse strains.

    PubMed

    Carp, R I; Meeker, H C; Chung, R; Kozak, C A; Hosokawa, M; Fujisawa, H

    2002-03-31

    A series of inbred strains of mice have been developed that are either prone (SAMP) or resistant (SAMR) to accelerated senescence. All of these strains originated from an inadvertent cross or crosses between the AKR/J mouse strain and an unknown strain(s). The characteristics of the nine senescence-prone lines differ, with all strains showing generalized aspects of accelerated aging but with each line having a specific aging-related change that is emphasized, e.g. learning and memory deficits, osteoporosis and senile amyloidosis. The senescence-resistant strains have normal patterns of aging and do not show the specific aging-related changes seen in SAMP strains. The fact that AKR mice have high levels of endogenous, ecotropic murine leukemia virus (MuLV) prompted an examination of the expression levels of MuLV in SAM strains. Analysis of brain, spleen and thymus samples revealed that seven of nine SAMP strains had high levels of MuLV and contained the Emv11 provirus (previously termed Akv1) that encodes the predominant MuLV found in AKR mice. In contrast, none of the SAMR strains had Emv11 or significant amounts of virus. The current findings represent an initial step in determining the role of MuLV in the accelerated senescence seen in SAMP strains. PMID:11850021

  4. Strain differences in the toxicity of cadmium to trigeminal ganglia in mice.

    PubMed

    Habeebu, S S; Liu, Y; Park, J D; Klaassen, C D

    2001-12-15

    Cadmium (Cd) is toxic to sensory ganglia in many animal species. Cadmium uptake is low in the central nervous system, but it distributes preferentially to peripheral sensory and autonomic ganglia. Strain differences have been demonstrated in the sensitivity of mice to Cd-induced hepatotoxicity, testicular toxicity, and teratogenicity. To study the sensitivity of different mouse strains to Cd toxicity in sensory ganglia, eight strains of mice (four sensitive to testicular toxicity: 129/SVIM, AKR/J, DBA/1J, and C57BR/J; and four resistant: Balb/C, C3H/HeJ, A/J, and C57BL/6J) were given 15 micromol CdCl(2)/kg iv. Trigeminal ganglia (TG) were harvested 24 h later and examined by light microscopy for pathologic lesions. Cadmium induced degeneration of ganglion cells in five strains, namely 129/SVIM, AKR/J, DBA/1J, C57BR/J, and C3H/HeJ mice. These are the same strains that show sensitivity to testicular toxicity, except for C3H/HeJ, which is resistant to testicular toxicity. Cd also induced focal hemorrhages around the ganglion cells and nerve fibers in two of these strains (129/SVIM and AKR/J) and scattered foci of necrosis in C3H/HeJ and 129/SVIM strains. There was no morphologic abnormality in three strains, namely Balb/C, A/J, and C57BL/6J. To examine the mechanism of these strain differences in toxicity, all eight strains of mice were given a nontoxic dose of Cd (0.4 micromol CdCl(2)/kg, 20 microCi (109)Cd/kg iv). Cadmium distribution to the brain and trigeminal ganglia was determined 30 min later by gamma scintillation spectrometry. Cadmium content in the brain was very low and did not differ among the eight strains. In contrast, Cd content was higher in trigeminal ganglia of four of the five strains showing trigeminal ganglia sensitivity than in the three strains showing resistance. In conclusion, the toxicity of Cd to trigeminal ganglia is different among various strains of mice. This strain difference in toxicity appears to be due, at least in part, to

  5. Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and -Resistant Helicobacter pylori Infections in Mice

    PubMed Central

    Jenks, Peter J.; Ferrero, Richard L.; Tankovic, Jacques; Thiberge, Jean-Michel; Labigne, Agnès

    2000-01-01

    The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P ≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P ≤ 0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice. PMID:10991835

  6. Some Properties of Heat-Resistant and Heat-Sensitive Strains of Clostridium perfringens I. Heat Resistance and Toxigenicity1

    PubMed Central

    Weiss, Karl F.; Strong, Dorothy H.

    1967-01-01

    Heat resistance at 100 C (D-values), sporulating ratios, toxigenicity for mice, and lecithinase activity (as micrograms per milliliter of enzyme, ascertained by the lecithovitellin reaction) were determined for four strains of Clostridium perfringens. A definite inverse relationship between thermal resistance and toxigenicity was found. The D-values ranged from 17.6 for the most heat-resistant strain to 0.3 for the strain possessing the least heat resistance, with corresponding lecithinase activities from 25 to 133 μg/ml of enzyme. The sporulating ratios did not differ greatly between the strains. The heat stability of the toxin was greater at 100 C than at 75 C. There was a noticeable difference between the heat stabilities of the toxin in the culture fluids of the heat-sensitive and heat-resistant strains at pH 7.0 when the toxic filtrates were held at 100 C. At a holding temperature of 75 C, a similar but lesser difference was observed at pH 5.5. Heat resistance and lecithinase activity did not change when a substrain of the least heat-resistant parent strain was obtained through heat selection by a single transfer, or when the most heat-resistant strain was transferred serially 12 times. PMID:4289809

  7. Expansion of the fetoplacental vasculature in late gestation is strain dependent in mice.

    PubMed

    Rennie, Monique Y; Detmar, Jacqui; Whiteley, Kathie J; Jurisicova, Andrea; Adamson, S Lee; Sled, John G

    2012-03-15

    How the fetoplacental arterial tree grows and expands during late gestational development is largely unknown. In this study, we quantified changes in arterial branching in the fetal exchange region of the mouse placenta during late gestation, when capillarization increases rapidly. We studied two commonly used mouse strains, CD1 and C57Bl/6 (B6), at embryonic days (E)13.5, 15.5, and 17.5. B6 mice differ from CD1 mice by exhibiting a blunted fetal weight gain in late gestation. We found that B6 capillarization and interhemal membrane thinning were reduced and placental hypoxia-inducible factor-1α and VEGF-A expression were higher than CD1 near term. Automated vascular segmentation of microcomputed tomography data sets revealed that the number of arterial vessels ≥50 μm remained constant during late gestation in both strains, despite large increases in downstream capillary volume quantified by stereology (+65% in B6 mice and +200% in CD1 mice). Arterial diameters expanded in both strains from E13.5 to E15.5; however, diameters continued to expand to E17.5 in B6 mice only. The diameter scaling coefficient at branch sites was near optimal (-3.0) and remained constant in CD1 mice, whereas it decreased, becoming abnormal, in B6 mice at term (-3.5 ± 0.2). Based on arterial tree geometry, resistance remained constant throughout late gestation (∼0.45 mmHg·s·μl(-1)) in CD1 mice, whereas it decreased by 50% in late gestation in B6 mice. Quantification of the fetoplacental vasculature revealed significant strain-dependent differences in arterial and capillary expansion in late gestation. In both strains, enlargement of the fetoplacental arterial tree occurred primarily by increased arterial diameters with no change in segment numbers in late gestation. PMID:22268107

  8. Acquired resistance to Giardia muris in X-linked immunodeficient mice.

    PubMed Central

    Skea, D L; Underdown, B J

    1991-01-01

    A previous study from this laboratory (D. P. Snider, D. Skea, and B. J. Underdown, Infect. Immun. 56:2838-2842, 1988) indicated that immunodeficient mice expressing the xid gene develop prolonged infections with Giardia muris, unlike immunocompetent mice, which eliminate the intestinal protozoan parasite in 8 to 10 weeks. In this study, CBA/N (xid) and CBA/Ca mice were infected with G. muris cysts and at various times following this primary infection were cured by treatment with metronidazole. In contrast to the marked differences in the ability of xid and normal mice to eliminate a primary infection, mice of both strains were resistant to a secondary challenge of G. muris cysts. These data imply that the mechanism(s) responsible for elimination of a primary infection is not identical to those required to resist a secondary challenge infection. Splenocytes from immunocompetent CBA/Ca mice (but not immunodeficient CBA/N mice) could transfer the ability to eliminate a primary G. muris infection to irradiated mice of either strain. In contrast, splenocytes from previously infected CBA/Ca mice could not transfer resistance to a challenge infection, further supporting the hypothesis that there are differences between mechanisms required to eliminate a primary infection and those necessary to resist a second challenge infection. PMID:2019439

  9. A study of the susceptibility of different mice strains to thio-TEPA: An experiment with recombinant strains

    SciTech Connect

    Malashenko, A.M.; Beskova, T.B.

    1995-07-01

    The study is devoted to the clastogenic effect of thio-TEPA in raising recombinant strains 1XC3 in mice (obtained from 101/H x C3H/Sn crossing). By the summer of 1993, 15 strains had reached 10 generations of inbreeding. Five to six sibs of each strain (males and females) aged 6-8 weeks were treated with the mutagen (3 mg/kg, i/p). Strain sensitivity was estimated by the frequency of marrow cells exhibiting chromosome lesions (including gaps). According to this characteristic, the strains were divided into two unequal groups. The first one included 12 less-sensitive strains (chromosome aberrations were present, on average, in 33.5% of the cells, and lay in the range from 27.0{+-}4.5 to 39.8{+-}4.9). The second group included three more-sensitive strains with 51.2, 51.7, and 59.5% of the cells being affected (54.1% on average). A similar difference between the groups was found with respect to the number of breaks per cell: 1.15 in resistant strains and 2.88 in sensitive ones. This difference was significant and similar to that found earlier for C3H and 101 strains. Thus, the results obtained support the hypothesis that mice of the 101/H strain carry a gene enhancing sensitivity to chemical mutagens (mut-l). Some strains of the first group were eliminated; the remaining ones will be bred until the 20th generation, when they will be investigated again in more detail. 24 refs., 1 fig., 2 tabs.

  10. An analysis of licking microstructure in three strains of mice

    PubMed Central

    Johnson, A.W.; Sherwood, A.; Smith, D.R.; Wosiski-Kuhn, M.; Gallagher, M.; Holland, P.C.

    2011-01-01

    Mouse models of feeding provide a useful tool for elucidating the molecular pathways of energy regulation. The majority of studies in mice have been limited to intake analyses conducted over extended periods of time, which fail to distinguish between a variety of factors that influence nutrient intake. Using licking microstructure analyses we examined both the size and number of licking bursts for water, polycose, sucrose and lecithin in three strains of mice (C57BL/6J, 129Sv/ImJ and C57129F1 hybrids), using pause criteria (250–500, >500 and >1000 ms) that have previously been described in the rat. Burst size and number varied both as a function of tastant concentration and mouse strain; however, these differences were most evident with the >1000 ms pause criterion. Consistent with previous reports, during water consumption C57 mice showed longer mean interlick intervals, a larger number of bursts but reduced burst size relative to the two other strains. F1 mice showed larger burst sizes for polycose, while C57 mice displayed a greater number of bursts for both polycose and sucrose. Both 129 and F1 mice were insensitive to sucrose concentration, whereas C57 mice showed attenuated lecithin intake influenced by a reduction in the size of bursts for this tastant. These results suggest that these strains of mice display differences in the pattern of licking that are most evident with the use of larger pause criteria. These differences in licking behavior might reflect influences of genetic background on pre- and post-ingestive factors controlling intake, the reinforcing properties of each tastant, or native differences in licking style. PMID:20006663

  11. Strain typing of U.S. scrapie strains using a panel of inbred mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion strains may vary in their ability to transmit to humans and animals. Few experimental studies have been done to provide evidence of differences between U.S. strains of scrapie, which can be distinguished by incubation times in inbred mice, microscopic lesions, immunoreactivity to various anti...

  12. Infectivity of hepatic strain Klebsiella pneumoniae in diabetic mice.

    PubMed

    Wu, June Hsieh; Tsai, Cheng Gie

    2005-11-01

    Besides urinary tract infection (UTI) and pneumonia, increased severe liver abscesses caused by Klebsiella pneumoniae (KP), especially in diabetic patients, have been observed in infections acquired in hospitals. This indicates that different KP strains with higher virulence have emerged in recent years. Our goal was to investigate the infectivity of KP isolates in mice from liver abscess or UTI patients. Mice were injected with streptozotocin to induce diabetes. Male ICR mice were infected with KpU1 (UTI strain CG3 for survival experiment only) and KpL1 (liver abscess strain CG5) by tail-vein injection of 5 x 10(4) colony-forming units (CFU) bacterial suspension. The mice survival rates, cytokine level by enzyme-linked immunosorbent assay (ELISA), and bacterial presence in liver tissue by Giemsa stain were examined. The survival rates for the KpL1-infected animals were 28% and 0% in normal and diabetic groups, respectively, whereas, for the KpU1-infected mice, the rates were 100% and 75% during a 30-day observation. Nonsurviving KpL1-infected mice showed > 10(5) bacteria/ml blood and the bacteria appeared in the liver sinus area and inside liver cells. The KpL1-infected mice showed a tendency to increase the blood interleukin 1beta (IL-1beta) level in both nondiabetic and diabetic groups, whereas the tumor necrosis factor-alpha (TNF-alpha) level was significantly decreased in the KpL1-infected diabetic mice (P = 0.002). In conclusion, the KP strain from liver abscess showed a greater virulence in mice than the KP from UTI and was more virulent in diabetic than in nondiabetic mice. The infection with KP from liver abscess significantly decreased the blood TNF-alpha level in diabetes mellitus (DM) mice and the blood IL-1beta level tended to increase in both infected nondiabetic and diabetic groups. High blood bacterial count and appearance of bacteria in liver sinus and cells usually contribute to death of the animals. PMID:16246903

  13. Antigenic Modification, Rosette-Forming Cells, and Salmonella typhimurium Resistance in Outbred and Inbred Mice

    PubMed Central

    Bigley, Nancy J.; Kreps, David P.; Smith, Randall A.; Esa, Ahmed

    1981-01-01

    To assess the separate contributions of host T cells and the physical state of the antigen in the development of effective. Salmonella resistance, glutaraldehyde-treated and untreated protein- and ribonucleic acid-rich extracts (E-RNA extracts) of virulent Salmonella typhimurium SR-11 or attenuated S. typhimurium RIA were used to immunize Salmonella-resistant Salmonella-susceptible strains of mice for the purpose of determining whether antigen-specific T-cell or B-cell responses were formed and, if so, which responses predominated. The resistance imparted to each mouse strain after vaccination with S. typhimurium RIA was used as the standard for comparison. The inbred mouse strains C57BL/6 and DBA/2 and their F1 hybrid (strain BDF1), outbred ICR Swiss mice, and endotoxin-resistant C3H/HeJ mice were examined for the capacity to develop resistance to lethal Salmonella infections, as well as the ability to generate antigen-reactive T cells. Only the BDF1, C3H/HeJ, and ICR Swiss mice were able to develop resistance to challenge infections mediated by the virulent SR-11 strain of S. typhimurium after vaccination with the living, attenuated RIA strain of S. typhimurium or immunization with E-RNA extracts. We developed an assay to identify the antigen-reactive rosette-forming lymphocytes present in lymph nodes and spleens of immunized mice. Levels of 0.2% or higher of theta antigen-bearing, antigen-reactive rosette-forming cells were found in the lymph nodes or spleens or both of only the BDF1, C3H/HeJ, and ICR Swiss mice (i.e., in the “Salmonella responder” strains). Mouse strains C57BL/6 and DBA/2, which failed to develop resistance to lethal infections after immunization with the S. typhimurium RIA vaccine or with the E-RNA extracts, lacked effective numbers of antitheta antigen-sensitive rosette-forming cells. Modification of the effective E-RNA extracts by polymerization with glutaraldehyde resulted in a marked diminution in their abilities to induce resistance

  14. An enriched environment improves cognitive performance in mice from the senescence-accelerated prone mouse 8 strain

    PubMed Central

    Yuan, Zhenyun; Wang, Mingwei; Yan, Baoyong; Gu, Ping; Jiang, Xiangming; Yang, Xiufen; Cui, Dongsheng

    2012-01-01

    In this study, we examined 3-month-old female mice from the senescence-accelerated prone mouse 8 strain and age-matched homologous normal aging female mice from the senescence accelerated- resistant mouse 1 strain. Mice from each strain were housed in an enriched environment (including a platform, running wheels, tunnel, and some toys) or a standard environment for 3 months. The mice housed in the enriched environment exhibited shorter escape latencies and a greater percentage of time in the target quadrant in the Morris water maze test, and they exhibited reduced errors and longer latencies in step-down avoidance experiments compared with mice housed in the standard environment. Correspondently, brain-derived neurotrophic factor mRNA and protein expression in the hippocampus was significantly higher in mice housed in the enriched environment compared with those housed in the standard environment, and the level of hippocampal brain-derived neurotrophic factor protein was positively correlated with the learning and memory abilities of mice from the senescence-accelerated prone mouse 8 strain. These results suggest that an enriched environment improved cognitive performance in mice form the senescence-accelerated prone mouse 8 strain by increasing brain-derived neurotrophic factor expression in the hippocampus. PMID:25624804

  15. Detection of immunoglobulin/c-myc recombinations in mice that are resistant to plasmacytoma induction.

    PubMed

    Müller, J R; Jones, G M; Potter, M; Janz, S

    1996-01-15

    Interchromosomal recombinations between c-myc and immunoglobulin sequences can be found in preneoplastic lesions (oil granulomata) during pristane-induced plasmacytoma development in susceptible BALB/cAn mice. In this study we used a more sensitive approach, hybridization-enriched templates with nested PCR, to detect microclones with Ig alpha/c-myc recombinations in oil granulomata of susceptible and resistant mice. Recombinations were detected in as many as 73% (32/44) of plasmacytoma-susceptible BALB/cAn mice 30 days after an injection of pristane. Mice that are resistant to plasmacytoma induction can also harbor recombination-positive cells, but these are less frequent [2/20 DBA/2N, 8/20 (BALB/cAn x DBA/2N)F1, hereafter called CD2F1]. The clones in DBA/2N mice were small (< 400 cells), whereas in BALB/cAn, the oil granuloma harbored up to several thousand of these cells. We conclude that the molecular machinery for generating characteristic interchromosomal recombinations can be found in all strains of mice. Both the frequency of generating Ig alpha/c-myc recombinations and the expansion of recombination-positive cells are greater in susceptible mice than in resistant strains. PMID:8542601

  16. More About High-Temperature Resistance Strain Gauges

    NASA Technical Reports Server (NTRS)

    Englund, D. R.; Williams, W. D.; Lei, Jih-Fen; Hulse, C. O.

    1994-01-01

    Two reports present additional information on electrical-resistance strain gauges described in "High-Temperature Resistance Strain Gauges" (LEW-15379). For protection against oxidation at high temperatures, gauges covered, by flame spraying, with coats of alumina containing up to 1 weight percent of yttria or, perferably, containing 4 to 6 weight percent of zirconia.

  17. Plant derived compounds inactivate antibiotic resistant Campylobacter jejuni strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sixty-three Campylobacter isolates were screened for their resistance to the antibiotics ampicillin, cefaclor, ciprofloxacin, erythromycin, gentamycin, tetracycline, and trimethroprim/sulfamethoxazole. Based on this screen, the resistant strains D28a and H2a and the nonresistant strain A24a were se...

  18. Drug resistance of organisms isolated from feces of laboratory mice and rats.

    PubMed

    Maejima, K; Urano, T; Tamura, H; Terakado, N

    1980-01-01

    A total of 248 strains of EScherichia coli, 132 of Staphylococcus epidermidis, 137 of Streptococcus faecalis and 89 of STr. faecium were collected from feces of 40 mice and 36 rats of 8 colonies in 1978, and drug resistance were examined by an agar dieution method using 23 antibiotics. The results indicated a positive relation between use of antibiotics and appearance of multiple drug resistant organisms. PMID:6772455

  19. [Behavior of mice from different strains: modifications produced by noopept].

    PubMed

    Bel'nik, A P; Ostrovskaia, R U; Poletaeva, I I

    2007-01-01

    Genotype-dependent behavioral effects were demonstrated in BALB/c, C57BL/6J [Russian character: see text] DBA/2J mice after injections of nootropic drug Noopept. In an elevated plus maze, drug administration induced an increase in the number of enterings into bright arms in BALB/c mice, whereas the opposite effect was observed in C57BL/6J. After the Noopept administration, animals from all the three strains increased the number of active avoidance reactions in stress-inducing slip-funnel test. A significant intensification of exploration behavior was observed in a closed plus-maze in BALB/c and C57BL/6J. The Noopept affected weakly or had no effect on the behavior of DBA/2J mice. PMID:18064900

  20. Enhanced resistance to acute infection with Trypanosoma cruzi in mice treated with an interferon inducer.

    PubMed Central

    James, S L; Kipnis, T L; Sher, A; Hoff, R

    1982-01-01

    For an exploration of the effects of interferon-inducible resistance mechanisms in acute American trypanosomiasis, the synthetic interferon inducer tilerone hydrochloride was administered to mice of the C57BL/6J strain, which is highly resistant to Trypanosoma cruzi, 18 to 24 h before infection with a potentially lethal dose of bloodstream trypomastigotes. Although all of the control mice died within 30 days of the acute infection, approximately 50% of the tilerone-treated animals were able to survive indefinitely (P less than 0.05). The tilerone-treated mice demonstrated significant levels of serum interferon and splenic natural killer cells at the time of infection. Macrophages isolated from the peritoneal cavities of tilerone-treated C57BL/6J mice appeared to kill significant numbers of trypanosomes during 2 to 3 days of in vitro culture, indicating that activated macrophages may contribute to the enhanced resistance to T. cruzi infection in these mice. Beige mice treated with tilerone did not survive T. cruzi infection as well as tilerone-treated heterozygotes did, suggesting a role for natural killer cells in interferon-induced resistance. These results suggest that interferon or effector mechanisms enhanced by interferon induction can play a significant role in influencing resistance to T. cruzi infection. PMID:6173326

  1. Compartmental responses after thoracic irradiation of mice: Strain differences

    SciTech Connect

    Chiang, C.-S.; Liu, W.-C.; Jung, S.-M.; Chen, F.-H.; Wu, C.-R.; McBride, William H.; Lee, C.-C.; Hong, J.-H. . E-mail: jihong@adm.cgmh.org.tw

    2005-07-01

    Purpose: To examine and compare the molecular and cellular processes leading to radiation fibrosis and pneumonitis in C57BL/6J and C3H/HeN mice. Methods and Materials: At indicated times after various doses of thoracic irradiation, the cell populations obtained by bronchoalveolar lavage of C57BL/6J mice were differentially analyzed by cytology and assessed by RNase protection (RPA) assay for levels of cytokines and related genes. The molecular responses in bronchial alveolar lavage (BAL) populations were compared with those in whole lung of C57BL/6J mice and with those of C3H/HeN mice. The former strain develops late radiation fibrosis, whereas the latter develop subacute radiation pneumonitis. Results: In C57BL/6J mice, a decrease in the total number of BAL cells was found 1 week after 6, 12, or 20 Gy thoracic irradiation with a subsequent dose-dependent increase up to 6 months. After 12 and 20 Gy, large, foamy macrophages and multinucleated cells became evident in BAL at 3 weeks, only to disappear at 4 months and reappear at 6 months. This biphasic response was mirrored by changes expression of mRNA for proinflammatory cytokines and the Mac-1 macrophage-associated antigen. As with BAL, whole lung tissue also showed biphasic cytokine and Mac-1 mRNA responses, but there were striking temporal differences between the two compartments, with changes in whole lung tissue correlating better than BAL with the onset of fibrosis in this strain. The radiation-induced proinflammatory mRNA responses had strain-dependent and strain-independent components. Thoracic irradiation of C3H/HeN induced similar increases in tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1{alpha}/{beta}, and interferon (IFN)-{gamma} mRNA expression in lung as it did in C57BL/6J mice during the 'presymptom' phase at 1-2 months. However, immediately preceding and during the pneumonitic time period at 3-4 months, TNF-{alpha} and IL-1{alpha}/{beta} mRNAs were highly upregulated in C3H/HeN mice, which

  2. A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice.

    PubMed

    Hosokawa, Masanori

    2002-11-01

    The SAM strain of mice is actually a group of related inbred strains consisting of series of SAMP (accelerated senescence-prone, short-lived) and SAMR (accelerated senescence-resistant, longer-lived) strains. Comparing with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans, including senile osteoporosis, degenerative joint disease, age-related deficits in learning and memory, olfactory bulb and forebrain atrophy, presbycusis and retinal atrophy, senile amyloidosis, immunosenescence, senile lungs, and diffuse medial thickening of the aorta. The higher oxidative stress observed in the SAMP strains of mice are partly caused by mitochondrial dysfunction, and may be one cause of the senescence acceleration and age-dependent alterations in cell structure and function, including neuronal cell degeneration. This senescence acceleration is also observed during senescence/crisis in cultures of isolated fibroblast-like cells from SAMP strains of mice, and was associated with a hyperoxidative status. These observations suggest that the SAM strains are useful tools in the attempt to understand the mechanisms of age-dependent degeneration of cells and tissues, and their aggravation, and to develop clinical interventions. PMID:12470893

  3. Fitness Studies of Azole-Resistant Strains of Aspergillus fumigatus.

    PubMed

    Valsecchi, Isabel; Mellado, Emilia; Beau, Rémi; Raj, Shriya; Latgé, Jean-Paul

    2015-12-01

    Isogenic bar-coded strains of Aspergillus fumigatus carrying the G54W or M220K mutation in Cyp51A were constructed. In vitro, the growth and conidiation capacities of the mutants were similar to those of the parental strain. Competition studies in the absence of azoles showed that there was no adverse fitness cost for the azole-resistant A. fumigatus strains in vitro or in vivo compared to the parental strain. PMID:26416854

  4. Fitness Studies of Azole-Resistant Strains of Aspergillus fumigatus

    PubMed Central

    Valsecchi, Isabel; Mellado, Emilia; Beau, Rémi; Raj, Shriya

    2015-01-01

    Isogenic bar-coded strains of Aspergillus fumigatus carrying the G54W or M220K mutation in Cyp51A were constructed. In vitro, the growth and conidiation capacities of the mutants were similar to those of the parental strain. Competition studies in the absence of azoles showed that there was no adverse fitness cost for the azole-resistant A. fumigatus strains in vitro or in vivo compared to the parental strain. PMID:26416854

  5. Bacteriophage-Resistant Staphylococcus aureus Mutant Confers Broad Immunity against Staphylococcal Infection in Mice

    PubMed Central

    Capparelli, Rosanna; Nocerino, Nunzia; Lanzetta, Rosa; Silipo, Alba; Amoresano, Angela; Giangrande, Chiara; Becker, Karsten; Blaiotta, Giuseppe; Evidente, Antonio; Cimmino, Alessio; Iannaccone, Marco; Parlato, Marianna; Medaglia, Chiara; Roperto, Sante; Roperto, Franco; Ramunno, Luigi; Iannelli, Domenico

    2010-01-01

    In the presence of a bacteriophage (a bacteria-attacking virus) resistance is clearly beneficial to the bacteria. As expected in such conditions, resistant bacteria emerge rapidly. However, in the absence of the phage, resistant bacteria often display reduced fitness, compared to their sensitive counterparts. The present study explored the fitness cost associated with phage-resistance as an opportunity to isolate an attenuated strain of S. aureus. The phage-resistant strain A172 was isolated from the phage-sensitive strain A170 in the presence of the MSa phage. Acquisition of phage-resistance altered several properties of A172, causing reduced growth rate, under-expression of numerous genes and production of capsular polysaccharide. In vivo, A172 modulated the transcription of the TNF-α, IFN-γ and Il-1β genes and, given intramuscularly, protected mice from a lethal dose of A170 (18/20). The heat-killed vaccine also afforded protection from heterologous methicillin-resistant S. aureus (MRSA) (8/10 mice) or vancomycin-intermediate S. aureus (VISA) (9/10 mice). The same vaccine was also effective when administered as an aerosol. Anti-A172 mouse antibodies, in the dose of 10 µl/mouse, protected the animals (10/10, in two independent experiments) from a lethal dose of A170. Consisting predominantly of the sugars glucose and galactose, the capsular polysaccharide of A172, given in the dose of 25 µg/mouse, also protected the mice (20/20) from a lethal dose of A170. The above results demonstrate that selection for phage-resistance can facilitate bacterial vaccine preparation. PMID:20661301

  6. Genome Analysis of 17 Extensively Drug-Resistant Strains Reveals New Potential Mutations for Resistance

    PubMed Central

    Tarazona, D.; Galarza, M.; Borda, V.; Curitomay, R.

    2014-01-01

    We report the whole-genome sequence of an extensively drug-resistant (XDR) tuberculosis (TB) strain of Latin American–Mediterranean (LAM) lineage. This strain is phenotypically resistant to aminoglycosides, but carries no related mutations in rrs, tlyA, and eis. Through genome analysis comparison with 16 XDR strains, we found 218 non-synonymous single nucleotide polymorphisms (SNPs) shared that could confer resistance. PMID:25081269

  7. Demonstration test of burner liner strain measurements using resistance strain gages

    NASA Technical Reports Server (NTRS)

    Grant, H. P.; Anderson, W. L.

    1984-01-01

    A demonstration test of burner liner strain measurements using resistance strain gages as well as a feasibility test of an optical speckle technique for strain measurement are presented. The strain gage results are reported. Ten Kanthal A-1 wire strain gages were used for low cycle fatigue strain measurements to 950 K and .002 apparent strain on a JT12D burner can in a high pressure (10 atmospheres) burner test. The procedure for use of the strain gages involved extensive precalibration and postcalibration to correct for cooling rate dependence, drift, and temperature effects. Results were repeatable within + or - .0002 to .0006 strain, with best results during fast decels from 950 K. The results agreed with analytical prediction based on an axisymmetric burner model, and results indicated a non-uniform circumferential distribution of axial strain, suggesting temperature streaking.

  8. Resistance-Strain Relation On Vanadium Dioxide Thin Films

    NASA Astrophysics Data System (ADS)

    Amiri, Ali; Leclair, Patrick; Gupta, Arun

    Vanadium dioxide is a strongly correlated material with a sharp metal to insulator transition at ~341 K. It is well known that the strain along c-axis can change the transition temperature, but the other effects of the strain have not been drawing much attention. In this work we have studied the effects of the strain on resistance changes in the polycrystalline and epitaxial films. Polycrystalline films of VO2 are deposited on the Pb(Mg1/3Nb2/3)0.72Ti0.28O3(001) (PMN-PT) using a SiO2 buffer layer. The strain on film is tuned by applying a bias electric field through the piezoelectric substrate, and the resistance is measured using four-probe method. The epitaxial films of VO2 are grown on TiO2 (001) and have been glued to PMN-PT substrate to transfer strain. The change in the resistance of the epitaxial films is measured to be only about 30% more than polycrystalline films for the same amount of strain. We have studied the strain-induced resistance changes as a function of temperature. we have shown that the resistance is more sensitive to strain in the metallic phase.

  9. 5-Fluorouracil-resistant strain of Methanobacterium thermoautortrophicum

    SciTech Connect

    Nagle, D.P. Jr.; Teal, R.; Eisenbraun, A.

    1987-09-01

    Growth of Methanobacterium thermoautotrophicum Marburg is inhibited by the pyrimidine, 5-fluorouracil (FU). It was shown previously that methanogenesis is not inhibited to the same extent as growth. A spontaneously occurring FU-resistant strain (RTAE-1) was isolated from a culture of strain Marburg. The growth of both strains was inhibited by 5-fluorodeoxyuridine but not 5-fluorocytosine, and the wild type was more susceptible to inhibition by 5-azauracil and 6-azauracil than was strain RTAE-1. The cellular targets for the pyrimidine analogs are not known. When the accumulation of /sup 14/C-labeled uracil or FU by the two strains was compared, the wilt type took up 15-fold more radiolabel per cell than did the FU-resistant strain. In the wild type, radiolabel from uracil was incorporated into the soluble pool, RNA, and DNA. The metabolism of uracil appeared to involve a uracil phosphoribosyltransferase activity. Strain Marburg extracts contained this enzyme, whereas FU-resistant strain RTAE-1 extracts had less than 1/10 as much activity. Although it is possible that a change in permeability to the compounds plays a role in the stable resistance of strain RTAE-1, the fact that it lacks the ability to metabolize pyrimidines to nucleotides is sufficient to account for its phenotype.

  10. Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains

    PubMed Central

    Teatero, Sarah; Patel, Samir N.

    2016-01-01

    Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS) data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12%) among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen. PMID:27559344

  11. Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains.

    PubMed

    Neemuchwala, Alefiya; Teatero, Sarah; Patel, Samir N; Fittipaldi, Nahuel

    2016-01-01

    Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS) data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12%) among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen. PMID:27559344

  12. Measurement of local values of strains of the briquette by means of special resistance strain gauges

    NASA Astrophysics Data System (ADS)

    Rysz, Jozef

    1997-02-01

    Local measurement of the coal briquette strains during its destruction caused by sudden decrease of pressure of gas filling pores is difficult, because of high strain of coal (exceeds 16%), which results in bursting. A special type of an resistance-strain gauge, which is pressed into a defined position during briquette preparation was elaborated. This gauge is deformed just as the surrounding coal. The strain is measured as a difference in resistance of a mixture of coal grains (briquette material) and short, 8 micrometers dia. graphite fibers. A ca. 0.5 mm thick and ca. 1 mm long gauge was prepared. Its initial resistance constituted several hundreds ohms. The resistance vs. strain dependence is not linear but stable enough in time and does not depend on the type of gas filling briquette pores (e.g. CO2 and He).

  13. Enamel crystals of mice susceptible or resistant to dental fluorosis: an AFM study

    PubMed Central

    BUZALAF, Marília Afonso Rabelo; BARBOSA, Carolina Silveira; LEITE, Aline de Lima; CHANG, Sywe-Ren; LIU, Jun; CZAJKA-JAKUBOWSKA, Agata; CLARKSON, Brian

    2014-01-01

    Objective This study aimed to assess the overall apatite crystals profile in the enamel matrix of mice susceptible (A/J strain) or resistant (129P3/J strain) to dental fluorosis through analyses by atomic force microscopy (AFM). Material and Methods Samples from the enamel matrix in the early stages of secretion and maturation were obtained from the incisors of mice from both strains. All detectable traces of matrix protein were removed from the samples by a sequential extraction procedure. The purified crystals (n=13 per strain) were analyzed qualitatively in the AFM. Surface roughness profile (Ra) was measured. Results The mean (±SD) Ra of the crystals of A/J strain (0.58±0.15 nm) was lower than the one found for the 129P3/J strain (0.66±0.21 nm) but the difference did not reach statistical significance (t=1.187, p=0.247). Crystals of the 129P3/J strain (70.42±6.79 nm) were found to be significantly narrower (t=4.013, p=0.0013) than the same parameter measured for the A/J strain (90.42±15.86 nm). Conclusion Enamel crystals of the 129P3/J strain are narrower, which is indicative of slower crystal growth and could interfere in the occurrence of dental fluorosis. PMID:25025555

  14. Applying strain into graphene by SU-8 resist shrinkage

    NASA Astrophysics Data System (ADS)

    Takamura, Makoto; Hibino, Hiroki; Yamamoto, Hideki

    2016-07-01

    We investigated the use of the shrinkage of SU-8 resist caused by thermal annealing to apply strain into graphene grown by the chemical-vapor-deposition (CVD) method. We demonstrate that the shrinkage of resist deposited on top of graphene on a substrate induces a local tensile strain within a distance of 1–2 μm from the edge of the resist. The thermal shrinkage of SU-8 will allow us to design the local strain in graphene on substrates. We also show that the shrinkage induces a large tensile strain in graphene suspended between two bars of SU-8. We expect that a much larger strain can be induced by suppressing defects in CVD-grown graphene.

  15. Photodynamic inactivation of antibiotic resistant strain of Pseudomonas aeruginosa in vivo

    NASA Astrophysics Data System (ADS)

    Hashimoto, M. C. E.; Toffoli, D. J.; Prates, R. A.; Courrol, Lilia C.; Ribeiro, M. S.

    2009-06-01

    Burns are frequently contamined by pathogenic microorganisms and the widespread occurrence of antibiotic resistant strains of Pseudomonas aeruginosa in hospitals is a matter of growing concern. Hypocrellin B (HB) is a new generation photosensitizer extracted from the fungus Hypocrella bambusae with absorption bands at 460, 546 and 584 nm. Lanthanide ions change the HB molecular structure and a red shift in the absorption band is observed as well as an increase in the singlet oxygen quantum yield. In this study, we report the use of HB:La+3 to kill resistant strain of P. aeruginosa infected burns. Burns were produced on the back of mice and wounds were infected subcutaneously with 1x109 cfu/mL of P. aeruginosa. Three-hours after inoculation, the animals were divided into 4 groups: control, HB:La+3, blue LED and HB:La+3+blue LED. PDT was performed using 10μM HB:La+3 and 500mW light-emitting diode (LED) emitting at λ=470nm+/-20nm during 120s. The animals of all groups were killed and the infected skin was removed for bacterial counting. Mice with photosensitizer alone, light alone or untreated infected wounds presented 1x108 cfu/g while mice PDT-treated showed a reduction of 2 logs compared to untreated control. These results suggest that HB:La+3 associated to blue LED is effective in diminishing antibiotic resistant strain P. aeruginosa in infected burns.

  16. SPECIES AND STRAIN COMPARISON OF ACUTE NEUROTOXIC EFFECTS OF TRIMETHYLTIN IN MICE AND RATS

    EPA Science Inventory

    Pathological changes in the central nervous system in two strains of mice (BALB/c and C57BL/6) and two strains of rats as a result of trimethyltin (TMT) intoxication were compared. Both strains of mice were administered with trimethyltin chloride at a dosage of 3.0 mg TMT-C1/kg b...

  17. [Eradication therapy of antibiotic-resistant strains of Helicobacter pylori].

    PubMed

    Shcherbakov, P L; Belousova, N L; Shcherbakova, M Iu; Kashnikov, V S

    2010-01-01

    Treatment of inflammatory diseases of the upper digestive tract, associated with Helicobacter pylori has recently greatly complicated by the presence of significant number of resistant strains of this microorganism to traditionally used drugs for eradication therapy. Average resistance to metronidazole and clarithromycin in Russia is about 30 and 25% respectively. The article presents the experience of treating patients with metronidazole resistant strains of H. pylori with using triple therapy, which included a drug used nitrofurans--nifuroxazide in suspension, proton pump inhibitors and clarithromycin. PMID:21485525

  18. Triple-material stress-strain resistivity gage

    DOEpatents

    Stout, R.B.

    1987-05-19

    A triple material piezoresistive gage provides multi-component elastic stress or strain measurements. Thin foils of three piezoresistive materials, e.g., ytterbium, manganin, and constantan, are configured in a nested serpentine rectilinear grind or other grind arrangement and embedded in a medium, preferably normal to the direction of shock wave propagation. The output of the gage is a resistivity change history for each material of gage. Each resistivity change is independent of the others so that three diagonal components of the elastic stress or strain tensor can be calculated form the resistivity measurements. 4 figs.

  19. Drug resistance analysis of bacterial strains isolated from burn patients.

    PubMed

    Wang, L F; Li, J L; Ma, W H; Li, J Y

    2014-01-01

    This study aimed to analyze the spectrum and drug resistance of bacteria isolated from burn patients to provide a reference for rational clinical use of antibiotics. Up to 1914 bacterial strain specimens isolated from burn patients admitted to hospital between 2001 and 2010 were subjected to resistance monitoring by using the K-B paper disk method. Retrospective analysis was performed on drug resistance analysis of burn patients. The top eight bacterium strains according to detection rate. A total of 1355 strains of Gram-negative (G(-)) bacteria and 559 strains of Gram-positive (G(+)) bacteria were detected. The top eight bacterium strains, according to detection rate, were Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, Klebsiella pneumoniae, Enterobacter cloacae, and Enterococcus. Drug resistance rates were higher than 90% in A. baumannii, P. aeruginosa, S. epidermidis, and S. aureus, which accounted for 52.2, 21.7, 27.8, and 33.3%, respectively, of the entire sample. Those with drug resistance rates lower than 30% accounted for 4.3, 30.4, 16.7, and 16.7%, respectively. Multidrug-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE) accounted for 49.2 and 76.4% of the S. epidermis and S. aureus resistance, respectively. Antibacterial drugs that had drug resistance rates to MRSE and MRSA higher than 90% accounted for 38.9 and 72.2%, respectively, whereas those with lower than 30% drug resistance rates accounted for 11.1 and 16.7%, respectively. The burn patients enrolled in the study were mainly infected with G(-) bacteria. These results strongly suggest that clinicians should practice rational use of antibiotics based on drug susceptibility test results. PMID:24535909

  20. Distinctive western blot antibody patterns induced by infection of mice with individual strains of the Mycobacterium avium complex.

    PubMed Central

    Elsaghier, A; Nolan, A; Allen, B; Ivanyi, J

    1992-01-01

    Systemic infection of mice with organisms of the Mycobacterium avium complex (MAC) induced antibody responses, characteristic for each of the three tested individual strains. The influence of host genetic factors was reflected up to 3 months after infection by the finding of generally oligobanded and multibanded Western blot patterns in C57B1/6 and BALB/c mice, respectively. Nevertheless, more bands developed at 6 months in C57BL/6 mice. The response to three antigens of 18,000, 38,000 and 24,000 MW was analysed in greater detail. Antibodies to a protease-resistant 18,000 MW band produced only by BALB/c mice were either strain specific, following infection with M. avium, strain Maa-B2, or cross-reactive within MAC, following infection with M. avium strain Maa-A6 and M. paratuberculosis, strain Map-203. Another protease-resistant antigen of 38,000 MW was immunogenic only in Maa-B2 infected mice. This constituent was found to be related to the protease-sensitive antigen of corresponding molecular weight from M. tuberculosis. Two 24,000 MW proteins of M. paratuberculosis were separated by two-dimensional gel electrophoresis: antibodies to the anodic band were induced by Map-203 infection, whilst the cathodic band was revealed by heteroclitic antibodies from Maa-B2-infected mice. The latter antigen is apparently expressed during in vivo replication, but not during in vitro culture of Maa-B2 bacteria. We generally conclude, that the selective antibody patterns after live infection, could be attributed to differences in the release of native antigens within mycobacterial lesions. In view of a high degree of species specificity, some of the immunogenic constituents identified may also be useful for serodiagnostic application. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1526646

  1. Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia.

    PubMed

    Gauguet, Stefanie; D'Ortona, Samantha; Ahnger-Pier, Kathryn; Duan, Biyan; Surana, Neeraj K; Lu, Roger; Cywes-Bentley, Colette; Gadjeva, Mihaela; Shan, Qiang; Priebe, Gregory P; Pier, Gerald B

    2015-10-01

    Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22(+) TCRβ(+) cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection. PMID:26216419

  2. A unique amyloidogenic apolipoprotein serum amyloid A (apoSAA) isoform expressed by the amyloid resistant CE/J mouse strain exhibits higher affinity for macrophages than apoSAA1 and apoSAA2 expressed by amyloid susceptible CBA/J mice.

    PubMed

    Liang, J; Elliott-Bryant, R; Hajri, T; Sipe, J D; Cathcart, E S

    1998-10-01

    CBA/J and other inbred strains of mice that express the amyloidogenic apolipoprotein serum amyloid A (apoSAA) apoSAA2, together with apoSAA1, are susceptible to amyloid A (AA) amyloidosis, whereas CE/J mice that express a single unique isoform, apoSAACEJ, are resistant. Studies indicate that CBA/JxCE/J hybrid mice that express apoSAA2 in the presence of apoSAACEJ are protected from amyloidogenesis. To define a mechanism by which expression of apoSAACEJ may protect from AA formation in the presence of apoSAA2, binding of recombinant apoSAA (r-apoSAA) isoforms, validated by N-terminal sequencing, to a murine macrophage cell line was investigated. Maximal specific binding occurred after incubation of radiolabeled apoSAA with IC-21 macrophages (1x105 cells/ml) for 30 min at 4 degreesC. The binding of 125I-r-apoSAA1, 125I-r-apoSAA2 and 125I-r-apoSAACEJ was specific and saturable, with an affinity (Kd) of about 2.8, 3.2 and 1.3 nM, respectively, and approximately 2-4x106 sites per cell. Competitive binding experiments indicate apoSAACEJ binds with higher affinity to macrophages than does either apoSAA1 or apoSAA2. We suggest that greater cellular affinity of apoSAACEJ compared to apoSAA2 may contribute to protection from AA amyloid in certain CBA/JxCE/J hybrid mice by interfering with interaction of apoSAA2 by macrophages and hence either membrane associated or intracellular degradation. PMID:9767146

  3. Characterization of the Resistance of SJL/J Mice to Pneumonia Virus of Mice, a Model for Infantile Bronchiolitis Due to a Respiratory Syncytial Virus

    PubMed Central

    Glineur, Stephanie; Tran Anh, Dao Bui; Sarlet, Michaël; Michaux, Charles; Desmecht, Daniel

    2012-01-01

    Respiratory syncytial virus (RSV), a prominent cause of airway morbidity in children, maintains an excessive hospitalization rate despite decades of research. Host factors are assumed to influence the disease severity. As a first step toward identifying the underlying resistance mechanisms, we recently showed that inbred mouse strains differ dramatically as regards their susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV. PVM infection in mice has been shown to faithfully mimic the severe RSV disease in human infants. This study aimed at dissecting the remarkable PVM-resistance shown by the SJL/J strain. To characterize its genetic component, we assessed clinical, physiopathological, and virological resistance/susceptibility traits in large first (F1) and second (F2) generations obtained by crossing the SJL/J (resistant) and 129/Sv (susceptible) strains. Then, to acquire conclusive in vivo evidence in support of the hypothesis that certain radiosensitive hematopoietic cells might play a significant role in PVM-resistance, we monitored the same resistance/susceptibility traits in mock- and γ-irradiated SJL/J mice. Segregation analysis showed that (i) PVM-resistance is polygenic, (ii) the resistance alleles are recessive, and (iii) all resistance-encoding alleles are concentrated in SJL/J. Furthermore, there was no alteration of SJL/J PVM-resistance after immunosuppression by γ-irradiation, which suggests that adaptive immunity is not involved. We conclude that host resistance to pneumoviruses should be amenable to genetic dissection in this mouse model and that radioresistant lung epithelial cells and/or alveolar macrophages may control the clinical severity of pneumovirus-associated lung disease. PMID:23077483

  4. Phage-resistant mutants of Lactobacillus delbrueckii may have functional properties that differ from those of parent strains.

    PubMed

    Vinderola, Gabriel; Marcó, Mariángeles Briggiler; Guglielmotti, Daniela M; Perdigón, Gabriela; Giraffa, Giorgio; Reinheimer, Jorge; Quiberoni, Andrea

    2007-05-01

    Three commercial phage sensitive Lactobacillus delbrueckii strains (identified as Ab(1), YSD V and Ib(3)), and four spontaneous phage-resistant mutants isolated from them were tested for their capacity to activate the gut mucosal immune response in mice, as indicated by the numbers of IgA-producing cells. Random Amplified Polymorphic DNA (RAPD) analysis revealed a strong genetic homology between the sensitive strains and their respective derivatives. The phage-resistant mutants exhibited high levels of phage resistance, elevated stability of this phenotype and technological properties comparable to those of their respective parent strains. The tolerance to acidic conditions, bile salts and lysozyme was strain dependent and total cell viability losses as a result of exposure to all three stresses ranged from 2.0 to 3.7 log units. All the strains were highly resistant to a simulated gastric solution of pH 3, while significant additional losses in cell viability were observed when acid treated cells were exposed to bile salts and lysozyme. BALB/c mice received pure cultures of Lb. delbrueckii sensitive and phage-resistant strains for 2, 5 or 7 consecutive days. The ability of the parent strains to activate the small intestine immune response was preserved or enhanced in phage-resistant mutants. The maximal proliferation of IgA(+) cells was observed at day 5 or 7, depending on the strain. Mutants isolated in this study using natural selection strategies had improved phage resistance, adequate technological properties and satisfactory gut mucosal immunostimulation ability, and so would be good candidates for industrial applications in functional foods. PMID:17307269

  5. [The preservation of strains of pathogenic Treponema pallidum in BALB/c mice].

    PubMed

    Bednova, V N; Ivlieva, M S; Milonova, T I; Stoianova, O A; Kamenetskaia, S B

    1990-01-01

    A clinical and serologic follow-up of 307 BALB/c mice and 12 rabbits injected with the blood and brain and spinal tissue of mice infected with 5 strains of T. pallidum has demonstrated the possibility of a prolonged (up to 465 days) preservation of pathogenic T. pallidum strains in these mice, as well as the regularity of a syphilitic infection development in rabbits. This permits recommending T. pallidum pathogenic strains to be maintained in mice at laboratories of institutions for skin and sexually transmitted diseases where experimental and diagnostic studies with the use of specific serologic tests for syphilis are carried out. PMID:2183519

  6. Resistance of functional Lactobacillus plantarum strains against food stress conditions.

    PubMed

    Ferrando, Verónica; Quiberoni, Andrea; Reinhemer, Jorge; Suárez, Viviana

    2015-06-01

    The survival of three Lactobacillus plantarum strains (Lp 790, Lp 813 and Lp 998) with functional properties was studied taking into account their resistance to thermal, osmotic and oxidative stress factors. Stress treatments applied were: 52 °C-15 min (Phosphate Buffer pH 7, thermal shock), H2O2 0.1% (p/v) - 30 min (oxidative shock) and NaCl aqueous solution at 17, 25 and 30% (p/v) (room temperature - 1 h, osmotic shock). The osmotic stress was also evaluated on cell growth in MRS broth added of 2, 4, 6, 8 and 10% (p/v) of NaCl, during 20 h at 30 °C. The cell thermal adaptation was performed in MRS broth, selecting 45 °C for 30 min as final conditions for all strains. Two strains (Lp 813 and Lp 998) showed, in general, similar behaviour against the three stress factors, being clearly more resistant than Lp 790. An evident difference in growth kinetics in presence of NaCl was observed between Lp 998 and Lp 813, Lp998 showing a higher optical density (OD570nm) than Lp 813 at the end of the assay. Selected thermal adaptation improved by 2 log orders the thermal resistance of both strains, but cell growth in presence of NaCl was enhanced only in Lp 813. Oxidative resistance was not affected with this thermal pre-treatment. These results demonstrate the relevance of cell technological resistance when selecting presumptive "probiotic" cultures, since different stress factors might considerably affect viability or/and performance of the strains. The incidence of stress conditions on functional properties of the strains used in this work are currently under research in our group. PMID:25790993

  7. Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine.

    PubMed

    Mukherjee, Pranab K; Leidich, Steven D; Isham, Nancy; Leitner, Ingrid; Ryder, Neil S; Ghannoum, Mahmoud A

    2003-01-01

    The in vitro antifungal susceptibilities of six clinical Trichophyton rubrum isolates obtained sequentially from a single onychomycosis patient who failed oral terbinafine therapy (250 mg/day for 24 weeks) were determined by broth microdilution and macrodilution methodologies. Strain relatedness was examined by random amplified polymorphic DNA (RAPD) analyses. Data obtained from both broth micro- and macrodilution assays were in agreement and revealed that the six clinical isolates had greatly reduced susceptibilities to terbinafine. The MICs of terbinafine for these strains were >4 microg/ml, whereas they were <0.0002 microg/ml for the susceptible reference strains. Consistent with these findings, the minimum fungicidal concentrations (MFCs) of terbinafine for all six strains were >128 microg/ml, whereas they were 0.0002 microg/ml for the reference strain. The MIC of terbinafine for the baseline strain (cultured at the initial screening visit and before therapy was started) was already 4,000-fold higher than normal, suggesting that this is a case of primary resistance to terbinafine. The results obtained by the broth macrodilution procedure revealed that the terbinafine MICs and MFCs for sequential isolates apparently increased during the course of therapy. RAPD analyses did not reveal any differences between the isolates. The terbinafine-resistant isolates exhibited normal susceptibilities to clinically available antimycotics including itraconazole, fluconazole, and griseofulvin. However, these isolates were fully cross resistant to several other known squalene epoxidase inhibitors, including naftifine, butenafine, tolnaftate, and tolciclate, suggesting a target-specific mechanism of resistance. This is the first confirmed report of terbinafine resistance in dermatophytes. PMID:12499173

  8. Clinical Trichophyton rubrum Strain Exhibiting Primary Resistance to Terbinafine

    PubMed Central

    Mukherjee, Pranab K.; Leidich, Steven D.; Isham, Nancy; Leitner, Ingrid; Ryder, Neil S.; Ghannoum, Mahmoud A.

    2003-01-01

    The in vitro antifungal susceptibilities of six clinical Trichophyton rubrum isolates obtained sequentially from a single onychomycosis patient who failed oral terbinafine therapy (250 mg/day for 24 weeks) were determined by broth microdilution and macrodilution methodologies. Strain relatedness was examined by random amplified polymorphic DNA (RAPD) analyses. Data obtained from both broth micro- and macrodilution assays were in agreement and revealed that the six clinical isolates had greatly reduced susceptibilities to terbinafine. The MICs of terbinafine for these strains were >4 μg/ml, whereas they were <0.0002 μg/ml for the susceptible reference strains. Consistent with these findings, the minimum fungicidal concentrations (MFCs) of terbinafine for all six strains were >128 μg/ml, whereas they were 0.0002 μg/ml for the reference strain. The MIC of terbinafine for the baseline strain (cultured at the initial screening visit and before therapy was started) was already 4,000-fold higher than normal, suggesting that this is a case of primary resistance to terbinafine. The results obtained by the broth macrodilution procedure revealed that the terbinafine MICs and MFCs for sequential isolates apparently increased during the course of therapy. RAPD analyses did not reveal any differences between the isolates. The terbinafine-resistant isolates exhibited normal susceptibilities to clinically available antimycotics including itraconazole, fluconazole, and griseofulvin. However, these isolates were fully cross resistant to several other known squalene epoxidase inhibitors, including naftifine, butenafine, tolnaftate, and tolciclate, suggesting a target-specific mechanism of resistance. This is the first confirmed report of terbinafine resistance in dermatophytes. PMID:12499173

  9. Virulence for mice, resistance to synthetic gastric fluid, and biofilm formation of Listeria monocytogenes H7550, a serotype 4b strain isolated from frankfurters associated with the BilMar listeriosis outbreak

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: One of the largest and most severe listeriosis outbreaks in the United States occurred in 1998 as a result of contamination of frankfurters with a serotype 4b strain of Listeria monocytogenes. However, there has been little characterization of the virulence attributes of strains reta...

  10. Dynamics of chromosomal aberrations in male mice of various strains during aging.

    PubMed

    Rozenfel'd, S V; Togo, E F; Mikheev, V S; Popovich, I G; Zabezhinskii, M A; Anisimov, V N

    2001-05-01

    We studied the incidence of chromosome aberrations in bone marrow cells and primary spermatocytes in various mouse strains. Experiments were performed on SAMP mice (accelerated aging), control SAMR mice, and long-living CBA and SHR mice. Experiments revealed a positive correlation between the age and the incidence of mutations in their somatic cells and gametes. PMID:11550060

  11. Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice

    PubMed Central

    Stöhr, Jan; Condello, Carlo; Watts, Joel C.; Bloch, Lillian; Oehler, Abby; Nick, Mimi; DeArmond, Stephen J.; Giles, Kurt; DeGrado, William F.; Prusiner, Stanley B.

    2014-01-01

    An increasing number of studies continue to show that the amyloid β (Aβ) peptide adopts an alternative conformation and acquires transmissibility; hence, it becomes a prion. Here, we report on the attributes of two strains of Aβ prions formed from synthetic Aβ peptides composed of either 40 or 42 residues. Modifying the conditions for Aβ polymerization increased both the protease resistance and prion infectivity compared with an earlier study. Approximately 150 d after intracerebral inoculation, both synthetic Aβ40 and Aβ42 prions produced a sustained rise in the bioluminescence imaging signal in the brains of bigenic Tg(APP23:Gfap-luc) mice, indicative of astrocytic gliosis. Pathological investigations showed that synthetic Aβ40 prions produced amyloid plaques containing both Aβ40 and Aβ42 in the brains of inoculated bigenic mice, whereas synthetic Aβ42 prions stimulated the formation of smaller, more numerous plaques composed predominantly of Aβ42. Synthetic Aβ40 preparations consisted of long straight fibrils; in contrast, the Aβ42 fibrils were much shorter. Addition of 3.47 mM (0.1%) SDS to the polymerization reaction produced Aβ42 fibrils that were indistinguishable from Aβ40 fibrils produced in the absence or presence of SDS. Moreover, the Aβ amyloid plaques in the brains of bigenic mice inoculated with Aβ42 prions prepared in the presence of SDS were similar to those found in mice that received Aβ40 prions. From these results, we conclude that the composition of Aβ plaques depends on the conformation of the inoculated Aβ polymers, and thus, these inocula represent distinct synthetic Aβ prion strains. PMID:24982137

  12. Triple-material stress-strain resistivity gage

    DOEpatents

    Stout, R.B.

    1988-05-17

    A triple material piezoresistive gage provides multi-component elastic stress measurements is disclosed. Thin foils of three piezoresistive materials, e.g. ytterbium, manganin, and constantan, are configured in a nested serpentine rectilinear grid or other grid arrangement and embedded in a medium, preferably normal to the direction of shock wave propagation. The output of the gage is a resistivity change history for each material of the gage. Each resistivity change is independent of the others so that three diagonal components of the elastic stress or strain tensor can be calculated from the resistivity measurements. 4 figs.

  13. Triple-material stress-strain resistivity gage

    DOEpatents

    Stout, Ray B.

    1988-01-01

    A triple material piezoresistive gage provides multi-component elastic stress or measurements. Thin foils of three piezoresistive materials, e.g. ytterbium, manganin, and constantan, are configured in a nested serpentine rectilinear grid or other grid arrangement and embedded in a medium, preferably normal to the direction of shock wave propagation. The output of the gage is a resistivity change history for each material of the gage. Each resistivity change is independent of the others so that three diagonal components of the elastic stress or strain tensor can be calculated from the resistivity measurements.

  14. Gentamicin resistance among Escherichia coli strains isolated in neonatal sepsis.

    PubMed

    Hasvold, J; Bradford, L; Nelson, C; Harrison, C; Attar, M; Stillwell, T

    2013-01-01

    Neonatal sepsis is a significant cause of morbidity and mortality among term and preterm infants. Ampicillin and gentamicin are standard empiric therapy for early onset sepsis. Four cases of neonatal sepsis secondary to Escherichia coli (E. coli) found to be gentamicin resistant occurred within a five week period in one neonatal intensive care unit (NICU). To determine whether these cases could be tied to a single vector of transmission, and to more broadly evaluate the incidence of gentamicin resistant strains of E. coli in the neonatal population at our institution compared to other centers, we reviewed the charts of the four neonates (Infants A through D) and their mothers. The E. coli isolates were sent for Pulse Field Gel Electrophoresis (PFGE) to evaluate for genetic similarity between strains. We also reviewed all positive E. coli cultures from one NICU over a two year period. Infants A and B had genetically indistinguishable strains which matched that of urine and placental cultures of Infant B's mother. Infant C had a genetically distinct organism. Infant D, the identical twin of Infant C, did not have typing performed. Review of all cultures positive for E. coli at our institution showed a 12.9 percent incidence of gentamicin-resistance. A review of other studies showed that rates of resistance vary considerably by institution. We conclude that gentamicin-resistant E. coli is a relatively uncommon cause of neonatal sepsis, but should remain a consideration in patients who deteriorate despite initiation of empiric antibiotics. PMID:24246520

  15. Chlorine inactivation of non-resistant and antibiotic resistant strains of Salmonella Typhimurium isolated from chicken carcasses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to test the hypothesis that strains of Salmonella Typhimurium that are resistant to antibiotics are more resistant to chlorine than strains of S. Typhimurium that are not resistant to antibiotics. To test this hypothesis, strains (n = 16) of S. Typhimurium with four antibiotic...

  16. Cigarette Smoke Induces Immune Responses to Vimentin in both, Arthritis-Susceptible and -Resistant Humanized Mice.

    PubMed

    Bidkar, Mitali; Vassallo, Robert; Luckey, David; Smart, Michele; Mouapi, Kelly; Taneja, Veena

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease marked by chronic synovial inflammation and both, genetic and environmental factors are involved in its pathogenesis. Human leukocyte antigen (HLA) DRB1*0401 is associated with susceptibility to develop RA, while cigarette smoke (CS) exposure promotes seropositive disease with increased severity in DRB1*0401+ individuals. Smokers have higher levels of antibodies against citrullinated peptides. In this study, we determined whether the response to a known autoantigen, Vimentin (Vim) is shared epitope specific and how CS influences this response using transgenic-mice carrying RA-susceptible,*0401, and -resistant, *0402, genes. Following relatively brief exposure to CS, peptidyl arginine deiminase (PAD) enzyme expression was increased in murine lungs. Cigarette smoking led to production of Interferon (IFN)-γ with reduced levels of Interleukin (IL)-10 by splenocytes of *0401 mice. In contrast, CS augmented Th2 cytokines along with T-regulatory cells in *0402 mice. An increase in levels of antibodies to native and citrullinated Vim was observed in naïve mice of both strains following CS exposure. Our data showed that both arthritis-susceptible and -resistant mice can generate cellular and humoral immunity to Vim; however CS-induced modulation of host immunity is dependent on the interaction with the host HLA genes. PMID:27602574

  17. Early hepatic insulin resistance in mice: a metabolomics analysis.

    PubMed

    Li, Lei O; Hu, Yun-Fu; Wang, Lily; Mitchell, Matthew; Berger, Alvin; Coleman, Rosalind A

    2010-03-01

    When fed with a high-fat safflower oil diet for 3 wk, wild-type mice develop hepatic insulin resistance, whereas mice lacking glycerol-3-phosphate acyltransferase-1 retain insulin sensitivity. We examined early changes in the development of insulin resistance via liver and plasma metabolome analyses that compared wild-type and glycerol-3-phosphate acyltransferase-deficient mice fed with either a low-fat or the safflower oil diet for 3 wk. We reasoned that diet-induced changes in metabolites that occurred only in the wild-type mice would reflect those metabolites that were specifically related to hepatic insulin resistance. Of the identifiable metabolites (from 322 metabolites) in liver, wild-type mice fed with the high-fat diet had increases in urea cycle intermediates, consistent with increased deamination of amino acids used for gluconeogenesis. Also increased were stearoylglycerol, gluconate, glucarate, 2-deoxyuridine, and pantothenate. Decreases were observed in S-adenosylhomocysteine, lactate, the bile acid taurocholate, and 1,5-anhydroglucitol, a previously identified marker of short-term glycemic control. Of the identifiable metabolites (from 258 metabolites) in plasma, wild-type mice fed with the high-fat diet had increases in plasma stearate and two pyrimidine-related metabolites, whereas decreases were found in plasma bradykinin, alpha-ketoglutarate, taurocholate, and the tryptophan metabolite, kynurenine. This study identified metabolites previously not known to be associated with insulin resistance and points to the utility of metabolomics analysis in identifying unrecognized biochemical pathways that may be important in understanding the pathophysiology of diabetes. PMID:20150186

  18. [Construction and characterization of a brucella suis S2 strain with a chloramphenicol resistance marker].

    PubMed

    Mao, Kai-Rong; Ding, Jia-Bo; Cheng, Jun-Sheng; Jiang, Yu-Wen; Yao, Wen-Sheng

    2007-12-01

    Vaccination has not been used widely because of the interference in the discrimination between infected and vaccinated animals in immune-screening procedures. In the present study, chloramphenicol resistance gene (Cm(r)) was cloned into the genomic DNA of brucella suis S2 strain by homologous recombination with knocking out the WbkC gene, and obtained the recombinant rS2-WbkC. Further study confirmed that rS2-WbkC was conversed into rough-phenotype form smooth-phenotype. The recombinant keeps the ability to chloramphenicol resistance after 25 passages in tryptic soy agar (TSA). Mice tests showed rS2-WbkC offered similar protection to S2 strain, but more safe than S2. Serum collected form rS2-WbkC immunized mice could be easily distinguished from antiserum produced by smooth-phenotype brucella abortus. In view of these result, rS2-WbkC is a promising candidate for vaccine strain. PMID:18271249

  19. The apparent strain stability and repeatability of a BCL3 resistance strain gage

    NASA Astrophysics Data System (ADS)

    Lei, Jih-Fen

    1991-02-01

    Experiments were conducted at NASA-Lewis to study the effect of microstructural instability on the apparent strain stability and reproducibility of a BCL3 resistance strain gage. The resistance drift of the gage at various temperatures in the phase transition temperature range (PTTR) was measured. The effects of the heating and cooling rates with which the gage passed through the PTTR on the apparent strain characteristics of the gage were also studied. BCL3 gage, like other Fe-Cr-Al based gages, exhibited apparent strain instability in the temperature range of 700 to 1100 F due to the reversible microstructural transition the gage materials experienced in this temperature range. The BCL3 gage had a maximum apparent strain drift in the neighborhood of 770 F with an average drift rate of approx. -440 microstrain/hr in 2 hrs. The use of the BCL3 gage as well as other Fe-Cl-Al based gages for static strain measurements within the PTTR should be avoided unless the time durations in the PTTR are small enough to introduce a neglible drift. The microstructure transition that the BCL3 gage underwent occurred in the temperature range of 750 to 1050 F during heating and around 1000 to 800 F during cooling. The heating rate, and, in particular, the cooling rate with which the gage passed through the PTTR affected the shape and the repeatability of the apparent strain curve of the gage.

  20. Evaluation of Brucella abortus S19 vaccine strains by bacteriological tests, molecular analysis of ery loci and virulence in BALB/c mice.

    PubMed

    Mukherjee, Falguni; Jain, Jainendra; Grilló, Maria Jesús; Blasco, José María; Nair, Mrinalini

    2005-09-01

    Two Brucella abortus S19 commercial vaccine strains used for vaccination against brucellosis in India and three S19 strains available as international reference were examined by microbiological assays and molecular analysis of the ery loci involved in erythritol metabolism, and tested for residual virulence in BALB/c mice. According to the sensitivity to penicillin and i-erythritol, the five strains tested had the phenotypic characteristics of strain S19. However, on culture medium containing i-erythritol, all strains developed spontaneous i-erythritol resistant colonies at mutation rates ranging from 1.42x10(-2) to 1.33x10(-6). The S19 characteristic 702 bp deletion in the erythrulose 1-phosphate dehydrogenase gene of the ery locus was present only in the three reference strains but not in the two commercial vaccines. Both commercial strains and one of the reference strains showed reduced virulence in BALB/c mice. The presence or absence in S19 strains of the 702 bp deletion in the ery locus had no correlation with either the rates of spontaneous mutation to erythritol resistance or the residual virulence in mice. PMID:16081301

  1. Resistance to cellular autophagy by Mycobacterium tuberculosis Beijing strains.

    PubMed

    Haque, Md Fazlul; Boonhok, Rachasak; Prammananan, Therdsak; Chaiprasert, Angkana; Utaisincharoen, Pongsak; Sattabongkot, Jetsumon; Palittapongarnpim, Prasit; Ponpuak, Marisa

    2015-10-01

    Autophagy represents a key pathway in innate immune defense to restrict Mycobacterium tuberculosis growth inside host macrophages. Induction of autophagy has been shown to promote mycobacterial phagosome acidification and acquisition of lysosomal hydrolases, resulting in the elimination of intracellular M. tuberculosis reference strains such as H37Rv. The notorious Beijing genotype has been previously shown to be hyper-virulent and associated with increased survival in host cells and a high mortality rate in animal models, but the underlying mechanism that renders this family to have such advantages remains unclear. We hypothesize that autophagic control against M. tuberculosis Beijing strains may be altered. Here, we discovered that the Beijing strains can resist autophagic killing by host cells compared with that of the reference strain H37Rv and a strain belonging to the East African Indian genotype. Moreover, we have determined a possible underlying mechanism and found that the greater ability to evade autophagic elimination possessed by the Beijing strains stems from their higher capacity to inhibit autophagolysosome biogenesis upon autophagy induction. In summary, a previously unrecognized ability of the M. tuberculosis Beijing strains to evade host autophagy was identified, which may have important implications for tuberculosis treatment, especially in regions prevalent by the Beijing genotype. PMID:26160686

  2. Biophysical separation of Staphylococcus epidermidis strains based on antibiotic resistance

    PubMed Central

    Jones, Paul V.; Huey, Shannon; Davis, Paige; McLemore, Ryan; McLaren, Alex

    2015-01-01

    Electrophoretic and dielectrophoretic approaches to separations can provide unique capabilities. In the past, capillary and microchip-based approaches to electrophoresis have demonstrated extremely high-resolution separations. More recently, dielectrophoretic systems have shown excellent results for the separation of bioparticles. Here we demonstrate resolution of a difficult pair of targets: gentamicin resistant and susceptible strains of Staphylococcus epidermidis. This separation has significant potential implications for healthcare. This establishes a foundation for biophysical separations as a direct diagnostic tool, potentially improving nearly every figure of merit for diagnostics and antibiotic stewardship. The separations are performed on a modified gradient insulator-based dielectrophoresis (g-iDEP) system and demonstrate that the presence of antibiotic resistance enzymes (or secondary effects) produces a sufficient degree of electrophysical difference to allow separation. The differentiating factor is the ratio of electrophoretic to dielectrophoretic mobilities. This factor is 4.6 ± 0.6 × 109 V m–2 for the resistant strain, versus 9.2 ± 0.4 × 109 V m–2 for the susceptible strain. Using g-iDEP separation, this difference produces clear and easily discerned differentiation of the two strains. PMID:26086047

  3. Biophysical separation of Staphylococcus epidermidis strains based on antibiotic resistance.

    PubMed

    Jones, Paul V; Huey, Shannon; Davis, Paige; Yanashima, Ryan; McLemore, Ryan; McLaren, Alex; Hayes, Mark A

    2015-08-01

    Electrophoretic and dielectrophoretic approaches to separations can provide unique capabilities. In the past, capillary and microchip-based approaches to electrophoresis have demonstrated extremely high-resolution separations. More recently, dielectrophoretic systems have shown excellent results for the separation of bioparticles. Here we demonstrate resolution of a difficult pair of targets: gentamicin resistant and susceptible strains of Staphylococcus epidermidis. This separation has significant potential implications for healthcare. This establishes a foundation for biophysical separations as a direct diagnostic tool, potentially improving nearly every figure of merit for diagnostics and antibiotic stewardship. The separations are performed on a modified gradient insulator-based dielectrophoresis (g-iDEP) system and demonstrate that the presence of antibiotic resistance enzymes (or secondary effects) produces a sufficient degree of electrophysical difference to allow separation. The differentiating factor is the ratio of electrophoretic to dielectrophoretic mobilities. This factor is 4.6 ± 0.6 × 10(9) V m(-2) for the resistant strain, versus 9.2 ± 0.4 × 10(9) V m(-2) for the susceptible strain. Using g-iDEP separation, this difference produces clear and easily discerned differentiation of the two strains. PMID:26086047

  4. Larvicide resistance in Musca domestica (Diptera: Muscidae) populations in Denmark and establishment of resistant laboratory strains.

    PubMed

    Kristensen, Michael; Jespersen, Jørgen B

    2003-08-01

    We determined the toxicity of the two IGRs, diflubenzuron and cyromazine, in this survey of resistance in Danish field populations of Musca domestica (L.). We observed resistance toward diflubenzuron and for the first time in Denmark and we found field populations with some resistance to cyromazine. Eleven of the twenty-one field populations had larvae surviving a diagnostic dose of 1.6 times of susceptible LC95 of diflubenzuron and two of these populations had larvae surviving 6.1 times of LC95. Eight of the twenty-one field populations had larvae surviving 2.2 times of susceptible LC95 of cyromazine and one population had larvae surviving 4.4 times of LC95. A fivefold cyromazine resistant strain was established after selection with cyromazine. It was 3-, 5-, and 90-fold resistant to diflubenzuron, triflumuron, and methoprene, respectively. Two diflubenzuron resistant strains (120- and 86-fold, respectively) were established. They showed a high level of resistance to triflumuron (1000- and 200-fold, respectively), and moderate resistance to methoprene (73- and 50-fold, respectively). Both were susceptible to cyromazine. This study shows that by applying the recommendations of previous resistance risk assessments, severe control failures and detrimental development of a high level of resistance have been avoided. The development of resistance has not been completely avoided, but has not developed to a level of biological or economic importance. PMID:14503604

  5. Effects of Streptococcus pneumoniae Strain Background on Complement Resistance

    PubMed Central

    Hyams, Catherine; Opel, Sophia; Hanage, William; Yuste, Jose; Bax, Katie; Henriques-Normark, Birgitta; Spratt, Brian G.; Brown, Jeremy S.

    2011-01-01

    Background Immunity to infections caused by Streptococcus pneumoniae is dependent on complement. There are wide variations in sensitivity to complement between S. pneumoniae strains that could affect their ability to cause invasive infections. Although capsular serotype is one important factor causing differences in complement resistance between strains, there is also considerable other genetic variation between S. pneumoniae strains that may affect complement-mediated immunity. We have therefore investigated whether genetically distinct S. pneumoniae strains with the same capsular serotype vary in their sensitivity to complement mediated immunity. Methodology and Principal Findings C3b/iC3b deposition and neutrophil association were measured using flow cytometry assays for S. pneumoniae strains with different genetic backgrounds for each of eight capsular serotypes. For some capsular serotypes there was marked variation in C3b/iC3b deposition between different strains that was independent of capsule thickness and correlated closely to susceptibility to neutrophil association. C3b/iC3b deposition results also correlated weakly with the degree of IgG binding to each strain. However, the binding of C1q (the first component of the classical pathway) correlated more closely with C3b/iC3b deposition, and large differences remained in complement sensitivity between strains with the same capsular serotype in sera in which IgG had been cleaved with IdeS. Conclusions These data demonstrate that bacterial factors independent of the capsule and recognition by IgG have strong effects on the susceptibility of S. pneumoniae to complement, and could therefore potentially account for some of the differences in virulence between strains. PMID:22022358

  6. Isolation of rifampicin resistant Flavobacterium psychrophilum strains and their potential as live attenuated vaccine candidates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have demonstrated that passage of pathogenic bacteria on increasing concentrations of the antibiotic rifampicin leads to the attenuation of virulence and these resistant strains may serve as live attenuated vaccines. Two rifampicin resistant strains of Flavobacterium psychrophilum,...

  7. EFFECT OF DIET AND STRAIN DIFFERENCE ON THE VIRULENCE OF STAPHYLOCOCCUS AUREUS FOR MICE.

    PubMed

    NUTINI, L G; BERBERICH, N J

    1965-07-01

    Years of intensive investigations in our laboratories on staphylococcal infections in mice have indicated a gradual decrease in the virulence of Staphylococcus aureus for this animal, particularly the strain we were using, the random-bred BT mouse. The present investigations, based on changes in diet and strain differences in mice, were undertaken in an attempt to improve susceptibility of our stock strain, on the one hand, and to determine whether susceptibility was influenced by genetic strain differences, on the other. In the first series of experiments, littermate mice of the BT strain were placed on different diets: one group received a commercial diet; the other, a basic diet previously established in our laboratories as adequate for growth requirements of the animals. An increase in the susceptibility of the animals to staphylococcal infection was noted in the mice receiving the basic diet. In the second series of investigations, three other strains of mice (the Swiss albino, the C3H/HeJ, and the C57B1) previously not used by our laboratories in staphylococcal experiments were studied for staphylococcal susceptibility. These experiments revealed that all of these strains of mice were highly susceptible to the infection, even though they were maintained on a commercial diet. PMID:14341596

  8. Genome Sequence of Lactobacillus johnsonii Strain W1, Isolated from Mice

    PubMed Central

    Wu, Xiaolin; Zhao, Chunyan; Guo, Zhonghe; Hao, Yuchong; Li, Jinghua; Shi, Hongyan

    2016-01-01

    Lactobacillus johnsonii, a member of the gut lactobacilli, plays an important role in normal gut functioning. Here, we report the draft genome sequence of L. johnsonii strain W1 isolated from ICR mice. PMID:27313302

  9. Role of major histocompatibility complex class II in resistance of mice to naturally acquired infection with Syphacia obvelata

    NASA Technical Reports Server (NTRS)

    Stewart, Patricia W.; Chapes, Stephen K.

    2003-01-01

    Genetics plays a substantial role in host resistance in many host-parasite interactions. We examined the prevalence of naturally acquired infection with Syphacia obvelata in a number of mouse strains housed in a non-barrier facility. These mice, which included cross-bred and congenic, inbred strains on various genetic backgrounds, differ in the loci for the immune function genes--major histocompatibility complex class II (MHCII), toll-like receptor 4 (Tlr4), and solute carrier family 11, member 1 (Slc11a1)--which allowed comparisons of the impact of these genes on resistance to pinworm infection. Male and female mice of various ages were sampled over an 18-month period; infection was determined by use of the cellophane tape test. Results indicated that mice that were MHCII+/+ had a significantly lower prevalence of infection than did mice that were MHCII-/-. Differences were not seen between male and female mice. Although MHCII+/+ mice had an age-associated decrease in infection prevalence, such decrease was not seen in MHCII-/- mice. In contrast, infection prevalence in mice with the normal Tlr4 gene (Tlr4(LPS-n/LPS-n)) gene did not differ significantly compared with that in mice that were homozygous for either the point mutation (Tlr4(LPS-d/LPS-d)) or deletion (Tlr4(LPS-del/LPS-del)) of that gene. Likewise, the presence (Sle11a1r/r) or absence (Slc11a1s/s) of functional alleles for Slc11a1 had no effect on the prevalence of infection with S. obvelata. In conclusion, presence of MHCII, but not Tlr4 or Slc11a1 significantly influences prevalence of naturally acquired infection with S. obvelata. These data justify further comprehensive analyses of the immune components that are involved in pinworm resistance.

  10. Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain

    PubMed Central

    Eldholm, Vegard; Monteserin, Johana; Rieux, Adrien; Lopez, Beatriz; Sobkowiak, Benjamin; Ritacco, Viviana; Balloux, Francois

    2015-01-01

    The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic. Yet, little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. Here we reconstruct the timeline of the acquisition of antimicrobial resistance during a major ongoing outbreak of multidrug-resistant TB in Argentina. We estimate that the progenitor of the outbreak strain acquired resistance to isoniazid, streptomycin and rifampicin by around 1973, indicating continuous circulation of a multidrug-resistant TB strain for four decades. By around 1979 the strain had acquired additional resistance to three more drugs. Our results indicate that Mycobacterium tuberculosis (Mtb) with extensive resistance profiles circulated 15 years before the outbreak was detected, and about one decade before the earliest documented transmission of Mtb strains with such extensive resistance profiles globally. PMID:25960343

  11. Immune responses in male mice with aggressive and submissive behavior patterns: strain differences.

    PubMed

    Devoino, L; Alperina, E; Kudryavtseva, N; Popova, N

    1993-03-01

    Immune responses in two strains of male mice with aggressive and submissive behavior patterns was studied. In aggressive CBA males immunized on the 10th day of agonistic confrontations with submissive partners, greater numbers of plaque-forming cells (PFC) and rosette-forming cells (RFC) were noted compared to control mice. Unlike the CBA strain, both PFC and RFC levels in aggressive C57BL males did not increase, but both PFC and RFC numbers decreased in submissive animals. PMID:8471801

  12. Resistance mechanism of Acinetobacter spp. strains resistant to DW-116, a new quinolone.

    PubMed

    Choi, K H; Baek, M C; Kim, B K; Choi, E C

    1998-06-01

    DW-116 is a new fluoroquinolone antimicrobial agent with a broad spectrum. In order to elucidate the resistance mechanism to DW-116 in Acinetobacter spp. bacteria, total chromosomal DNA was isolated from 10 strains of Acinetobacter spp. resistant to DW-116. Quinolone resistance determinant region (QRDR) of DNA gyrase gene was amplified by PCR. The 345 bp nucleotide fragment yielded was inserted into pKF 3 which was used as the vector. Comparisons of the DNA sequences of 8 strains with that of the wild type strain revealed a Ser-83 to Leu mutation in mutants and all ten strains contained one silent mutation(T-->G) in QRDR. From Acinetobacter MB4-8 strain, DNA gyrase was isolated and purified, through no-vobiocin-sepharose, heparin-sepharose affinity column chromatography. The enzyme was composed of two subunits and the molecular mass of subunits A and B were 75.6 and 51.9 kDa, respectively. The supercoiling activity of the reconstituted DNA gyrase composed of subunit A from Acinetobacter MB4-8 and subunit B from E. coli was not inhibited by 128 micrograms/ml of ciprofloxacin. It might be said that one of the resistance mechanisms to DW-116 in A-cinetobacter MB4-8 was subunit A alteration of DNA gyrase. PMID:9875449

  13. Oral immunization of mice with recombinant rabies vaccine strain (ERAG3G) induces complete protection

    PubMed Central

    2015-01-01

    Purpose New rabies vaccine bait for both pets and raccoon dogs residing in Korea is needed to eradicate rabies infection among animals. In this study, we constructed a recombinant rabies virus (RABV), the ERAG3G strain, using a reverse genetics system. Then we investigated the efficacy of this strain in mice after oral administration and the safety of this strain in cats after intramuscular administration. Materials and Methods The ERAG3G strain was rescued in BHK/T7-9 cells using the full-length genome mutated at the amino acid position 333 of the glycoprotein gene of RABV and helper plasmids. Four-week-old mice underwent one or two oral administrations of the ERAG3G strain and were challenged with the highly virulent RABV strain CVSN2c 14 days after the second administration. Clinical symptoms were observed and body weights were measured every day after the challenge. Results All mice showed complete protection against virulent RABV. In addition, cats intramuscularly inoculated with the ERAG3G strain showed high antibody titers ranging from 2.62 to 23.9 IU/mL at 28-day postinoculation. Conclusion The oral immunization of the ERAG3G strain plays an important role in conferring complete protection in mice, and intramuscular inoculation of the ERAG3G strain induces the formation of anti-rabies neutralizing antibody in cats. PMID:25648184

  14. Strain-Specific Regulation of Striatal Phenotype in Drd2-eGFP BAC Transgenic Mice

    PubMed Central

    Chan, C. Savio; Peterson, Jayms D.; Gertler, Tracy S.; Glajch, Kelly E.; Quintana, Ruth E.; Cui, Qiaoling; Sebel, Luke E.; Plotkin, Joshua L.; Shen, Weixing; Heiman, Myriam; Heintz, Nathaniel; Greengard, Paul; Surmeier, D. James

    2012-01-01

    Mice carrying bacterial artificial chromosome (BAC) transgenes have become important tools for neuroscientists, providing a powerful means of dissecting complex neural circuits in the brain. Recently, it was reported that one popular line of these micemice possessing a BAC transgene with a D2 dopamine receptor (Drd2) promoter construct coupled to an enhanced green fluorescent protein (eGFP) reporter – had abnormal striatal gene expression, physiology and motor behavior. Unlike most of the work using BAC mice, this interesting study relied upon mice backcrossed on the outbred Swiss Webster strain that were homozygous for the Drd2-eGFP BAC transgene.The experiments reported here were conducted to determine whether mouse strain or zygosity was a factor in the reported abnormalities. As reported, SW mice were very sensitive to transgene expression. However, in more commonly used inbred strains of mice (C57BL/6, FVB/N) that were hemizygous for the transgene, the Drd2-eGFP BAC transgene did not alter striatal gene expression, physiology or motor behavior. Thus, the use of inbred strains of mice which are hemizygous for the Drd2 BAC transgene provide a reliable tool for studying basal ganglia function. PMID:22764222

  15. Regulatory T cells control strain specific resistance to Experimental Autoimmune Prostatitis.

    PubMed

    Breser, Maria L; Lino, Andreia C; Motrich, Ruben D; Godoy, Gloria J; Demengeot, Jocelyne; Rivero, Virginia E

    2016-01-01

    Susceptibility to autoimmune diseases results from the encounter of a complex and long evolved genetic context with a no less complex and changing environment. Major actors in maintaining health are regulatory T cells (Treg) that primarily dampen a large subset of autoreactive lymphocytes escaping thymic negative selection. Here, we directly asked whether Treg participate in defining susceptibility and resistance to Experimental Autoimmune Prostatitis (EAP). We analyzed three common laboratory strains of mice presenting with different susceptibility to autoimmune prostatitis upon immunization with prostate proteins. The NOD, the C57BL/6 and the BALB/c mice that can be classified along a disease score ranging from severe, mild and to undetectable, respectively. Upon mild and transient depletion of Treg at the induction phase of EAP, each model showed an increment along this score, most remarkably with the BALB/c mice switching from a resistant to a susceptible phenotype. We further show that disease associates with the upregulation of CXCR3 expression on effector T cells, a process requiring IFNγ. Together with recent advances on environmental factors affecting Treg, these findings provide a likely cellular and molecular explanation to the recent rise in autoimmune diseases incidence. PMID:27624792

  16. Immune responses and resistance to brucellosis in mice vaccinated orally with Brucella abortus RB51.

    PubMed Central

    Stevens, M G; Olsen, S C; Palmer, M V; Pugh, G W

    1996-01-01

    Immune responses and resistance to infection with Brucella abortus 2308 (S2308) were measured in mice following oral or intraperitoneal (i.p.) vaccination with strain RB51 (SRB51). Bacteria persisted in the parotid lymph node for 4 weeks following oral vaccination of mice with 5 x 10(8) or 5 x 10(6) CFU of SRB51. Bacteria did not appear in the spleen during 12 weeks after oral vaccination, whereas they did appear in the spleen for 8 weeks following i.p. vaccination of mice with SRB51 (5 x 10(8) or 5 x 10(6) CFU). Increased resistance to S2308 infection occurred at 12 to 20 weeks in mice vaccinated i.p. with SRB51 (5 x 10(8) or 5 x 10(6) CFU) but occurred at 12 weeks only in mice vaccinated orally with SRB51 (5 x 10(8) CFU). Oral SRB51 vaccination induced lower levels of antibodies to the surface antigens of intact SRB51 bacteria than did i.p. vaccination. However, neither route of vaccination induced anamnestic antibody responses to the surface antigens of intact S2308 bacteria after challenge infection of the vaccinated mice with S2308. Mice vaccinated orally with SRB51 and challenged with S2308 at 12 to 20 weeks had lower and less persistent spleen cell proliferation and production of gamma interferon in response to S2308 and certain immunodominant S2308 proteins (32 to < or = 18 kDa) than did mice vaccinated i.p. with SRB51. However, mice vaccinated orally or i.p. with SRB51 and challenged with S2308 had similar spleen cell tumor necrosis factor alpha production. These results indicate that oral vaccination of mice with SRB51 was effective in inducing protective immunity to S2308 infection, although the immunity was lower and less persistent than that induced by i.p. vaccination. The lower protective immunity induced by oral vaccination may have resulted from lower and less persistent cell-mediated immunity and gamma interferon production in response to S2308 and S2308 proteins. PMID:8890203

  17. Transcriptomic comparison of thiamethoxam-resistance adaptation in resistant and susceptible strains of Aphis gossypii Glover.

    PubMed

    Pan, Yiou; Peng, Tianfei; Gao, Xiwu; Zhang, Lei; Yang, Chen; Xi, Jinghui; Xin, Xuecheng; Bi, Rui; Shang, Qingli

    2015-03-01

    A thiamethoxam-resistant strain of cotton aphid (ThR) strain displayed a 19.35-fold greater resistance to thiamethoxam compared to a susceptible cotton aphid (SS) strain. Solexa sequencing technology was used to investigate differentially expressed genes (DEGs) in cotton aphids in the context of thiamethoxam resistance. A total of 22,569,311 and 21,317,732 clean reads were obtained from the ThR and SS transcriptomes, respectively, and assembled into 35,222 non-redundant (Nr) consensus sequences. The expression of 620 unigenes changed significantly in the ThR libraries compared to the SS strain; 349 genes were up-regulated, and 271 genes were down-regulated (P≤0.001). Expression levels of ribosomal proteins, ATP synthase, cytochrome c oxidase, ecdysteroid UDP-glucosyltransferase and esterase were up-regulated significantly in the ThR strain compared to the SS strain. The genes of cuticle proteins, salivary proteins, and fibroin heavy chain decreased dramatically. One nicotinic acetylcholine receptor (nAChR) α subunit was down-regulated in the ThR strain. The expression levels of 10 differentially expressed unigenes were confirmed using real-time RT-PCR, and the observed trends in gene expression matched the Solexa expression profiles. Specific single-nucleotide polymorphisms (SNPs) in nAChRs that cause amino acid substitution were found from the ThR and SS stains respectively. These data illustrate that genetic changes in nAChR genes and up-regulated ribosomal proteins, ecdysteroid UDP-glucosyltransferase, cytochrome c oxidase, esterase and peroxidase may confer the tolerance of resistant cotton aphids to thiamethoxam. PMID:25528611

  18. Mycobacterium tuberculosis gene Rv2136c is dispensable for acid resistance and virulence in mice

    PubMed Central

    Darby, Crystal M.; Venugopal, Aditya; Ehrt, Sabine; Nathan, Carl F.

    2011-01-01

    Summary The gene Rv2136c is annotated to encode the Mycobacterium tuberculosis (Mtb) homologue of Escherichia coli’s undecaprenyl pyrophosphate phosphatase. In previous work, a genetic screen of 10,100 Mtb transposon mutants identified Rv2136c as being involved in acid resistance in Mtb. The Rv2136c:Tn strain was also sensitive to sodium dodecyl sulfate, lipophilic antibiotics, elevated temperature and reactive oxygen and nitrogen intermediates and was attenuated for growth and persistence in mice. However, none of these phenotypes could be genetically complemented, leading us to generate an Rv2136c knockout strain to test its role in Mtb pathogenicity. Genetic deletion revealed that Rv2136c is not responsible for any of the phenotypes observed in the transposon mutant strain. An independent genomic mutation is likely to have accounted for the extreme attenuation of this strain. Identification of the mutated gene will further our understanding of acid resistance mechanisms in Mtb and may offer a target for anti-tuberculosis chemotherapy. PMID:21778115

  19. Heavy metal resistant strains are widespread along Streptomyces phylogeny.

    PubMed

    Alvarez, Analía; Catalano, Santiago A; Amoroso, María Julia

    2013-03-01

    The genus Streptomyces comprises a group of bacteria species with high economic importance. Several of these species are employed at industrial scale for the production of useful compounds. Other characteristic found in different strains within this genus is their capability to tolerate high level of substances toxic for humans, heavy metals among them. Although several studies have been conducted in different species of the genus in order to disentangle the mechanisms associated to heavy metal resistance, little is known about how they have evolved along Streptomyces phylogeny. In this study we built the largest Streptomyces phylogeny generated up to date comprising six genes, 113 species of Streptomyces and 27 outgroups. The parsimony-based phylogenetic analysis indicated that (i) Streptomyces is monophyletic and (ii) it appears as sister clade of a group formed by Kitasatospora and Streptacidiphilus species, both genera also monophyletic. Streptomyces strains resistant to heavy metals are not confined to a single lineage but widespread along Streptomyces phylogeny. Our result in combination with genomic, physiological and biochemical data suggest that the resistance to heavy metals originated several times and by different mechanisms in Streptomyces history. PMID:23247041

  20. The potential for enhanced fungicide resistance in Beauveria bassiana through strain discovery and artificial selection.

    PubMed

    Shapiro-Ilan, David I; Reilly, Charles C; Hotchkiss, Michael W; Wood, Bruce W

    2002-10-01

    Our objectives were to determine the (1) natural variation in fungicide resistance among Beauveria bassiana strains, (2) potential to increase fungicide resistance in B. bassiana through artificial selection, and (3) stability of virulence in selected B. bassiana strains. Fungicides included dodine, fenbuconazole, and triphenyltin hydroxide, which are commonly used in pecan and other horticultural crops. Comparison of seven B. bassiana strains indicated some are substantially more resistant to fungicides than others; a commercial strain (GHA) was less resistant than all wild strains isolated from pecan orchards. Artificial selection resulted in enhanced fungicide resistance in the GHA strain but not in a mixed wild strain. Removal of selection pressure for three passages did not reduce the enhanced fungicide resistance. Sub-culturing with exposure to fungicides did not affect the GHA strain's virulence to pecan weevil, Curculio caryae, larvae, whereas fungicide exposure increased virulence in a mixed wild population of B. bassiana. PMID:12445792

  1. The Effect of Ivermectin in Seven Strains of Aedes aegypti (Diptera: Culicidae) Including a Genetically Diverse Laboratory Strain and Three Permethrin Resistant Strains

    PubMed Central

    Deus, K. M.; Saavedra-rodriguez, K.; Butters, M. P.; Black, W. C.; Foy, B. D.

    2014-01-01

    Seven different strains of Aedes aegypti (L.), including a genetically diverse laboratory strain, three laboratory-selected permethrin-resistant strains, a standard reference strain, and two recently colonized strains were fed on human blood containing various concentrations of ivermectin. Ivermectin reduced adult survival, fecundity, and hatch rate of eggs laid by ivermectin-treated adults in all seven strains. The LC50 of ivermectin for adults and the concentration that prevented 50% of eggs from hatching was calculated for all strains. Considerable variation in adult survival after an ivermectin-bloodmeal occurred among strains, and all three permethrin-resistant strains were significantly less susceptible to ivermectin than the standard reference strain. The hatch rate after an ivermectin bloodmeal was less variable among strains, and only one of the permethrin-resistant strains differed significantly from the standard reference strain. Our studies suggest that ivermectin induces adult mortality and decreases the hatch rate of eggs through different mechanisms. A correlation analysis of log-transformed LC50 among strains suggests that permethrin and ivermectin cross-resistance may occur. PMID:22493855

  2. Accurate Detection of Rifampicin-Resistant Mycobacterium Tuberculosis Strains.

    PubMed

    Song, Keum-Soo; Nimse, Satish Balasaheb; Kim, Hee Jin; Yang, Jeongseong; Kim, Taisun

    2016-01-01

    In 2013 alone, the death rate among the 9.0 million people infected with Mycobacterium tuberculosis (TB) worldwide was around 14%, which is unacceptably high. An empiric treatment of patients infected with TB or drug-resistant Mycobacterium tuberculosis (MDR-TB) strain can also result in the spread of MDR-TB. The diagnostic tools which are rapid, reliable, and have simple experimental protocols can significantly help in decreasing the prevalence rate of MDR-TB strain. We report the evaluation of the 9G technology based 9G DNAChips that allow accurate detection and discrimination of TB and MDR-TB-RIF. One hundred and thirteen known cultured samples were used to evaluate the ability of 9G DNAChip in the detection and discrimination of TB and MDR-TB-RIF strains. Hybridization of immobilized probes with the PCR products of TB and MDR-TB-RIF strains allow their detection and discrimination. The accuracy of 9G DNAChip was determined by comparing its results with sequencing analysis and drug susceptibility testing. Sequencing analysis showed 100% agreement with the results of 9G DNAChip. The 9G DNAChip showed very high sensitivity (95.4%) and specificity (100%). PMID:26999135

  3. Accurate Detection of Rifampicin-Resistant Mycobacterium Tuberculosis Strains

    PubMed Central

    Song, Keum-Soo; Nimse, Satish Balasaheb; Kim, Hee Jin; Yang, Jeongseong; Kim, Taisun

    2016-01-01

    In 2013 alone, the death rate among the 9.0 million people infected with Mycobacterium tuberculosis (TB) worldwide was around 14%, which is unacceptably high. An empiric treatment of patients infected with TB or drug-resistant Mycobacterium tuberculosis (MDR-TB) strain can also result in the spread of MDR-TB. The diagnostic tools which are rapid, reliable, and have simple experimental protocols can significantly help in decreasing the prevalence rate of MDR-TB strain. We report the evaluation of the 9G technology based 9G DNAChips that allow accurate detection and discrimination of TB and MDR-TB-RIF. One hundred and thirteen known cultured samples were used to evaluate the ability of 9G DNAChip in the detection and discrimination of TB and MDR-TB-RIF strains. Hybridization of immobilized probes with the PCR products of TB and MDR-TB-RIF strains allow their detection and discrimination. The accuracy of 9G DNAChip was determined by comparing its results with sequencing analysis and drug susceptibility testing. Sequencing analysis showed 100% agreement with the results of 9G DNAChip. The 9G DNAChip showed very high sensitivity (95.4%) and specificity (100%). PMID:26999135

  4. Immunization against Multidrug-Resistant Acinetobacter baumannii Effectively Protects Mice in both Pneumonia and Sepsis Models

    PubMed Central

    Huang, Weiwei; Yao, Yufeng; Long, Qiong; Yang, Xu; Sun, Wenjia; Liu, Cunbao; Jin, Xiaomei; li, Yang; Chu, Xiaojie; Chen, Bin; Ma, Yanbing

    2014-01-01

    Objective Acinetobacter baumannii is considered the prototypical example of a multi- or pan- drug-resistant bacterium. It has been increasingly implicated as a major cause of nosocomial and community-associated infections. This study proposed to evaluate the efficacy of immunological approaches to prevent and treat A. baumannii infections. Methods Mice were immunized with outer membrane vesicles (OMVs) prepared from a clinically isolated multidrug-resistant strain of A. baumannii. Pneumonia and sepsis models were used to evaluate the efficacy of active and passive immunization with OMVs. The probable effective mechanisms and the protective potential of clonally distinct clinical isolates were investigated in vitro using an opsonophagocytic assay. Results Intramuscular immunization with OMVs rapidly produced high levels of OMV-specific IgG antibodies, and subsequent intranasal challenge with A. baumannii elicited mucosal IgA and IgG responses. Both active and passive immunization protected the mice from challenges with homologue bacteria in a sepsis model. Bacterial burden in bronchoalveolar lavage fluids (BALF), lung, and spleen, inflammatory cell infiltration in BALF and lung, and inflammatory cytokine accumulation in BALF was significantly suppressed in the pneumonia model by both active and passive immunization strategies. The antisera from immunized mice presented with significant opsonophagocytic activities in a dose-dependent manner against not only homologous strains but also five of the other six clonally distinct clinical isolates. Conclusions Utilizing immunological characteristics of outer membrane proteins to elevate protective immunity and circumvent complex multidrug-resistance mechanisms might be a viable approach to effectively control A. baumannii infections. PMID:24956279

  5. Radial maze performance in three strains of mice - Role of the fimbria/fornix

    NASA Technical Reports Server (NTRS)

    Reinstein, D. K.; Deboissiere, T.; Robinson, N.; Wurtman, R. J.

    1983-01-01

    Three strains of mice were tested on an 8-arm radial maze, an index of hippocampus-dependent spatial memory. Levels of performance differed betweens strains with C57Br/cdj greater than Balb/cj greater than C57B1/6j. Lesions of the fimbria/fornix disrupted performance in the C57Br and Balb strains: the C57Bl mice never performed better than chance before or after surgery. Choline acetyltransferase activity in hippocampus was not correlated with radial maze performance. These findings suggest a possible genetic contribution towards radial maze behavior.

  6. Comparative Fitness of a Parent Leishmania donovani Clinical Isolate and Its Experimentally Derived Paromomycin-Resistant Strain

    PubMed Central

    Hendrickx, Sarah; Leemans, Annelies; Mondelaers, Annelies; Rijal, Suman; Khanal, Basudha; Dujardin, Jean-Claude; Delputte, Peter; Cos, Paul; Maes, Louis

    2015-01-01

    Paromomycin has recently been introduced for the treatment of visceral leishmaniasis and emergence of drug resistance can only be appropriately judged upon its long term routine use in the field. Understanding alterations in parasite behavior linked to paromomycin-resistance may be essential to assess the propensity for emergence and spread of resistant strains. A standardized and integrated laboratory approach was adopted to define and assess parasite fitness of both promastigotes and amastigotes using an experimentally induced paromomycin-resistant Leishmania donovani strain and its paromomycin-susceptible parent wild-type clinical isolate. Primary focus was placed on parasite growth and virulence, two major components of parasite fitness. The combination of in vitro and in vivo approaches enabled detailed comparison of wild-type and resistant strains for which no differences could be demonstrated with regard to promastigote growth, metacyclogenesis, in vitro infectivity, multiplication in primary peritoneal mouse macrophages and infectivity for Balb/c mice upon infection with 2 x 107 metacyclic promastigotes. Monitoring of in vitro intracellular amastigote multiplication revealed a consistent decrease in parasite burden over time for both wild-type and resistant parasites, an observation that was subsequently also confirmed in a larger set of L. donovani clinical isolates. Though the impact of these findings should be further explored, the study results suggest that the epidemiological implications of acquired paromomycin-resistance may remain minimal other than the loss of one of the last remaining drugs effective against visceral leishmaniasis. PMID:26469696

  7. Capsaicin Protects Mice from Community-Associated Methicillin-Resistant Staphylococcus aureus Pneumonia

    PubMed Central

    Xing, Yan; Leng, Bingfeng; Dong, Jing; Li, Hongen; Luo, Mingjing; Zhang, Yu; Dai, Xiaohan; Luo, Yonghuang; Deng, Xuming

    2012-01-01

    Background α-toxin is one of the major virulence factors secreted by most Staphylococcus aureus strains, which played a central role in the pathogenesis of S. aureus pneumonia. The aim of this study was to investigate the impact of capsaicin on the production of α-toxin by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA 300 and to further assess its performance in the treatment of CA-MRSA pneumonia in a mouse model. Methodology/Principal Findings The in vitro effects of capsaicin on α-toxin production by S. aureus USA 300 were determined using hemolysis, western blot, and real-time RT-PCR assays. The influence of capsaicin on the α-toxin-mediated injury of human alveolar epithelial cells was determined using viability and cytotoxicity assays. Mice were infected intranasally with S. aureus USA300; the in vivo protective effects of capsaicin against S. aureus pneumonia were assessed by monitoring the mortality, histopathological changes and cytokine levels. Low concentrations of capsaicin substantially decreased the production of α-toxin by S. aureus USA 300 without affecting the bacterial viability. The addition of capsaicin prevented α-toxin-mediated human alveolar cell (A549) injury in co-culture with S. aureus. Furthermore, the in vivo experiments indicated that capsaicin protected mice from CA-MRSA pneumonia caused by strain USA 300. Conclusions/Significance Capsaicin inhibits the production of α-toxin by CA-MRSA strain USA 300 in vitro and protects mice from CA-MRSA pneumonia in vivo. However, the results need further confirmation with other CA-MRSA lineages. This study supports the views of anti-virulence as a new antibacterial approach for chemotherapy. PMID:22427935

  8. Devising assisted reproductive technologies for wild-derived strains of mice: 37 strains from five subspecies of Mus musculus.

    PubMed

    Mochida, Keiji; Hasegawa, Ayumi; Otaka, Naoki; Hama, Daiki; Furuya, Takashi; Yamaguchi, Masaki; Ichikawa, Eri; Ijuin, Maiko; Taguma, Kyuichi; Hashimoto, Michiko; Takashima, Rika; Kadota, Masayo; Hiraiwa, Noriko; Mekada, Kazuyuki; Yoshiki, Atsushi; Ogura, Atsuo

    2014-01-01

    Wild-derived mice have long offered invaluable experimental models for mouse genetics because of their high evolutionary divergence from laboratory mice. A number of wild-derived strains are available from the RIKEN BioResource Center (BRC), but they have been maintained as living stocks because of the unavailability of assisted reproductive technology (ART). In this study, we sought to devise ART for 37 wild-derived strains from five subspecies of Mus musculus maintained at the BRC. Superovulation of females was effective (more than 15 oocytes per female) for 34 out of 37 strains by treatment with either equine chorionic gonadotropin or anti-inhibin serum, depending on their genetic background (subspecies). The collected oocytes could be fertilized in vitro at mean rates of 79.0% and 54.6% by the optimized protocol using fresh or frozen-thawed spermatozoa, respectively. They were cryopreserved at the 2-cell stage by vitrification with an ethylene glycol-based solution. In total, 94.6% of cryopreserved embryos survived the vitrification procedure and restored their normal morphology after warming. A conventional embryo transfer protocol could be applied to 25 out of the 35 strains tested. In the remaining 10 strains, live offspring could be obtained by a modified embryo transfer protocol using cyclosporin A treatment and co-transfer of ICR (laboratory mouse strain) embryos. Thus, ART for 37 wild-derived strains was devised successfully and is now routinely used for their preservation and transportation. The information provided here might facilitate broader use and wider distribution of wild-derived mice for biomedical research. PMID:25470728

  9. [The appearance of ciprofloxacin resistance in the microbial strains isolated from gynecologic patients].

    PubMed

    Shopova, E

    1997-01-01

    The sensitivity of 415 microbial strains isolated from clinically taken samples from gynecologically diseased women was determined. The urine strains showed sensitivity up to 93.3%, but 7 Gram/-/ strains isolated in the last 3 months of the study were resistant to Ciprofloxacin. The cervical secretion strains, those of CD aspirates, of IUP and wound secretions were found sensitive up to 81.2%. The 50 Enterococcus strains isolated in gynecological infections were found in 28% resistant to Ciprofloxacin, with 7 of the 19 resistant strains were isolated in the last 3 months of the study. The appearance of resistant strains in some microbial species, pointed out in the literature as markedly sensitivity to Ciprofloxacin, as well as the data of a fast developed resistance Ciprofloxacin in the course of treatment, allowed us to recommend their application in the infections caused by microorganisms resistant to the habitual antibiotics. PMID:9289951

  10. Live Attenuated Borrelia burgdorferi Targeted Mutants in an Infectious Strain Background Protect Mice from Challenge Infection.

    PubMed

    Hahn, Beth L; Padmore, Lavinia J; Ristow, Laura C; Curtis, Michael W; Coburn, Jenifer

    2016-08-01

    Borrelia burgdorferi, B. garinii, and B. afzelii are all agents of Lyme disease in different geographic locations. If left untreated, Lyme disease can cause significant and long-term morbidity, which may continue after appropriate antibiotic therapy has been administered and live bacteria are no longer detectable. The increasing incidence and geographic spread of Lyme disease are renewing interest in the vaccination of at-risk populations. We took the approach of vaccinating mice with two targeted mutant strains of B. burgdorferi that, unlike the parental strain, are avirulent in mice. Mice vaccinated with both strains were protected against a challenge with the parental strain and a heterologous B. burgdorferi strain by either needle inoculation or tick bite. In ticks, the homologous strain was eliminated but the heterologous strain was not, suggesting that the vaccines generated a response to antigens that are produced by the bacteria both early in mammalian infection and in the tick. Partial protection against B. garinii infection was also conferred. Protection was antibody mediated, and reactivity to a variety of proteins was observed. These experiments suggest that live attenuated B. burgdorferi strains may be informative regarding the identification of protective antigens produced by the bacteria and recognized by the mouse immune system in vivo Further work may illuminate new candidates that are effective and safe for the development of Lyme disease vaccines. PMID:27335385

  11. Isolation and Characterization of Multiply Antibiotic-Resistant Clostridium perfringens Strains from Porcine Feces

    PubMed Central

    Rood, Julian I.; Maher, Eileen A.; Somers, Eileen B.; Campos, Elena; Duncan, Charles L.

    1978-01-01

    Multiply antibiotic-resistant strains of Clostridium perfringens were isolated from porcine feces. Strains that were resistant to tetracycline, erythromycin, clindamycin, and lincomycin were isolated, but no penicillin- or chloramphenicol-resistant strains were obtained. Typical minimal inhibitory concentrations for resistant strains were 16 to 64 μg of tetracycline per ml, 64 to >128 μg of erythromycin per ml, ≥128 μg of lincomycin per ml, and 16 to 128 μg of clindamycin per ml. Resistance to erythromycin was always associated with resistance to lincomycin and clindamycin. Minimal inhibitory concentrations were determined for 258 strains from six farms that used antibiotics in their feeds and 240 strains from five farms that did not use antibiotics. The results show that 77.9 and 22.7% of the strains from the former farms were resistant to tetracycline and erythromycin-clindamycin-lincomycin, respectively. The comparable data from the latter farms were 25.0 and 0.8%, respectively. Agarose gel electrophoresis failed to reveal a plasmid band that was common to the resistant strains but absent in the susceptible strains. Attempts to transfer tetracycline, erythromycin, and clindamycin resistance from one strain, CW459, were not successful. Antibiotic-susceptible mutants were not isolated from this strain, despite the use of a variety of curing agents. Images PMID:208463

  12. Genetic basis for nitrate resistance in Desulfovibrio strains

    PubMed Central

    Korte, Hannah L.; Fels, Samuel R.; Christensen, Geoff A.; Price, Morgan N.; Kuehl, Jennifer V.; Zane, Grant M.; Deutschbauer, Adam M.; Arkin, Adam P.; Wall, Judy D.

    2014-01-01

    Nitrate is an inhibitor of sulfate-reducing bacteria (SRB). In petroleum production sites, amendments of nitrate and nitrite are used to prevent SRB production of sulfide that causes souring of oil wells. A better understanding of nitrate stress responses in the model SRB, Desulfovibrio vulgaris Hildenborough and Desulfovibrio alaskensis G20, will strengthen predictions of environmental outcomes of nitrate application. Nitrate inhibition of SRB has historically been considered to result from the generation of small amounts of nitrite, to which SRB are quite sensitive. Here we explored the possibility that nitrate might inhibit SRB by a mechanism other than through nitrite inhibition. We found that nitrate-stressed D. vulgaris cultures grown in lactate-sulfate conditions eventually grew in the presence of high concentrations of nitrate, and their resistance continued through several subcultures. Nitrate consumption was not detected over the course of the experiment, suggesting adaptation to nitrate. With high-throughput genetic approaches employing TnLE-seq for D. vulgaris and a pooled mutant library of D. alaskensis, we determined the fitness of many transposon mutants of both organisms in nitrate stress conditions. We found that several mutants, including homologs present in both strains, had a greatly increased ability to grow in the presence of nitrate but not nitrite. The mutated genes conferring nitrate resistance included the gene encoding the putative Rex transcriptional regulator (DVU0916/Dde_2702), as well as a cluster of genes (DVU0251-DVU0245/Dde_0597-Dde_0605) that is poorly annotated. Follow-up studies with individual D. vulgaris transposon and deletion mutants confirmed high-throughput results. We conclude that, in D. vulgaris and D. alaskensis, nitrate resistance in wild-type cultures is likely conferred by spontaneous mutations. Furthermore, the mechanisms that confer nitrate resistance may be different from those that confer nitrite resistance

  13. Drug resistance and R plasmids in Escherichia coli strains isolated from imported pet birds.

    PubMed

    Nakamura, M; Fukazawa, M; Yoshimura, H; Koeda, T

    1980-01-01

    Drug resistance in Escherichia coli strains isolated from pet birds (mynahs, macaws, finches, common bengals, parrots, and flamingos) imported into Japan from 10 foreign countries in 1977 and 1978 was investigated. Of the 309 strains isolated from 127 pet birds in the Animal Quarantine Service, 232 (75.1%) were drug resistant. Furthermore, strains resistant to oxytetracycline hydrochloride, dihydrostreptomycin, and sulfadimethoxine were relatively common. Resistance patterns varied from single to sextuple resistance, and 148 (63.8%) of the resistant strains had conjugative R plasmids. These results suggest that the high incidence of drug resistance and R plasmids in E. coli strains isolated from these pet birds may be a reflection of the prophylactic use of antibiotics for the prevention of diseases which increasingly occur with importation of the birds. Furthermore, the results suggest that the birds may be potential reservoirs of drug-resistant E. coli for families who raise and have intimate contact with such birds. PMID:6163947

  14. Response of liver and kidney adenylate kinase to fasting and refeeding in three strains of mice.

    PubMed

    Chinn-Norris, E; Russell, P J; Lopez, A; Urias, L

    1986-01-01

    The effects of fasting and refeeding on the AK isozymes in liver and kidney were studied in three strains of mice. Our studies showed that changes in total AK activity and AK isozyme patterns were associated with fasting and refeeding. The AK isozyme changes were strain-dependent, differing in kind and degree among the three strains. It was concluded that species, strain and individual isozyme identities should be included in studies defining changes of enzyme activity owing to changes in physiological conditions. PMID:3015484

  15. Beta-lactamase gene expression in a penicillin-resistant Bacillus anthracis strain.

    PubMed

    Chen, Yahua; Tenover, Fred C; Koehler, Theresa M

    2004-12-01

    Expression of the bla1 and bla2 genes in an archetypal Bacillus anthracis strain is insufficient for penicillin resistance. In a penicillin-resistant clinical isolate, both genes are highly transcribed, but bla1 is the major contributor to high-level resistance to ampicillin. Differential expression of the bla genes is dependent upon strain background. PMID:15561870

  16. Strain-dependency of leukotriene C4 generation from isolated lungs of immunized mice.

    PubMed Central

    Zuany-Amorim, C.; Vargaftig, B. B.; Maclouf, J.; Pretolani, M.

    1994-01-01

    1. The antigen-induced leukotriene C4 (LTC4)-like-material release from isolated perfused lungs of actively sensitized Swiss, Balb/C and CBA/J mice was compared. The intra-tracheal (i.t.) instillation of 1 and 100 micrograms ovalbumin to lungs from Swiss mice was followed by a dose-dependent generation of LTC4-like material into the effluent, as detected by radio-immunoassay and h.p.l.c., followed by an enzyme-immunoassay. In contrast, lungs from sensitized Balb/C and CBA/J mice failed to exhibit LTC4-like-material release in amounts above the basal values. No histamine secretion was observed when lungs of the three strains of mice were challenged with ovalbumin. 2. The i.t. instillation of 1 or 10 micrograms platelet-activating factor (PAF) or of 100 micrograms arachidonic acid to lungs from non-sensitized mice, induced the release of comparable amounts of LTC4-like-material in the effluent, irrespective to the strain. However, N-formyl-L-methionyl-L-leucyl-L- phenylalanine (fMLP, 0.1, 10 micrograms), was more effective in inducing the release of LTC4-like-material from lung from Swiss and CBA, than from Balb/C, mice. 3. The intraplantar injection of 0.01 microgram ovalbumin to sensitized Swiss mice induced an intense oedema formation, as measured plethysmographically, while Balb/C mice required a dose of antigen at least 10 fold higher for a similar response. CBA/J mice did not respond to antigen challenge in terms of oedema formation. The intraplantar injection of PAF or fMLP to non-immunized mice induced an oedema of similar intensity in all the strains considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7524994

  17. Prevalence and antibiotic resistance of Enterococcus strains isolated from poultry.

    PubMed

    Stępień-Pyśniak, Dagmara; Marek, Agnieszka; Banach, Tomasz; Adaszek, Łukasz; Pyzik, Ewelina; Wilczyński, Jarosław; Winiarczyk, Stanisław

    2016-06-01

    The aim of this study was to evaluate the frequency of occurrence of bacteria of the genus Enterococcus in poultry, to identify them by means of matrixassisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF MS), and to analyse the antimicrobial susceptibility of the isolated strains to the drugs most frequently used in poultry. The material for the bacteriological tests was obtained mainly from the heart (97%) of the birds investigated. Of a total of 2,970 samples tested, 911 (30.7%) tested positive for Enterococcus spp. Enterococci were detected in broilers (88.1%), laying hens (5.3%), turkeys (3.9%), breeding hens (2.2%), and geese (0.4%). The most commonly identified species were Enterococcus (E.) faecalis (74.7%), E. faecium (10.1%), E. gallinarum (5.5%), E. hirae (4.6%), and E. cecorum (4.1%). The most frequent resistance properties were resistance to sulphamethoxazole/trimethoprim (88%), tylosin (71.4%), enrofloxacin (69.4%), doxycycline (67.3%), and lincomycin/spectinomycin (56.1%). Only one vancomycin-resistant Enterococcus, E. cecorum from a broiler, was found. PMID:27342087

  18. Effects of roxithromycin on fecal bacteria in human volunteers and resistance to colonization in gnotobiotic mice.

    PubMed Central

    Pecquet, S; Chachaty, E; Tancrède, C; Andremont, A

    1991-01-01

    The ecological impact of roxithromycin given orally at 300 mg/day on the intestinal floras in six human volunteers was studied. The resulting fecal concentrations of active roxithromycin were in the range of 100 to 200 micrograms/g of feces. Consecutive modifications in the composition of the fecal floras were limited to a decrease in counts of total members of the family Enterobacteriaceae. The rest of the intestinal floras, including the predominant anaerobic floras, changed little. No overgrowth of Pseudomonas aeruginosa, staphylococci, fungi, or highly erythromycin-resistant strains of the family Enterobacteriaceae was observed. The strains of Enterobacteriaceae and of anaerobes isolated during treatment were not markedly more resistant to roxithromycin than those isolated before treatment started. Changes in intestinal resistance to colonization by exogenous microorganisms in gnotobiotic mice inoculated with human fecal flora were studied and were also found to be minimal. The impact of oral roxithromycin on the intestinal microbiota appears to be weaker than that previously observed with oral erythromycin, perhaps because the concentrations of roxithromycin in the feces were lower than those previously found for erythromycin. PMID:2039207

  19. Obesity impairs lactation performance in mice by inducing prolactin resistance

    PubMed Central

    Buonfiglio, Daniella C.; Ramos-Lobo, Angela M.; Freitas, Vanessa M.; Zampieri, Thais T.; Nagaishi, Vanessa S.; Magalhães, Magna; Cipolla-Neto, Jose; Cella, Nathalie; Donato Jr., Jose

    2016-01-01

    Obesity reduces breastfeeding success and lactation performance in women. However, the mechanisms involved are not entirely understood. In the present study, female C57BL/6 mice were chronically exposed to a high-fat diet to induce obesity and subsequently exhibited impaired offspring viability (only 15% survival rate), milk production (33% reduction), mammopoiesis (one-third of the glandular area compared to control animals) and postpartum maternal behaviors (higher latency to retrieving and grouping the pups). Reproductive experience attenuated these defects. Diet-induced obese mice exhibited high basal pSTAT5 levels in the mammary tissue and hypothalamus, and an acute prolactin stimulus was unable to further increase pSTAT5 levels above basal levels. In contrast, genetically obese leptin-deficient females showed normal prolactin responsiveness. Additionally, we identified the expression of leptin receptors specifically in basal/myoepithelial cells of the mouse mammary gland. Finally, high-fat diet females exhibited altered mRNA levels of ERBB4 and NRG1, suggesting that obesity may involve disturbances to mammary gland paracrine circuits that are critical in the control of luminal progenitor function and lactation. In summary, our findings indicate that high leptin levels are a possible cause of the peripheral and central prolactin resistance observed in obese mice which leads to impaired lactation performance. PMID:26926925

  20. Obesity impairs lactation performance in mice by inducing prolactin resistance.

    PubMed

    Buonfiglio, Daniella C; Ramos-Lobo, Angela M; Freitas, Vanessa M; Zampieri, Thais T; Nagaishi, Vanessa S; Magalhães, Magna; Cipolla-Neto, Jose; Cella, Nathalie; Donato, Jose

    2016-01-01

    Obesity reduces breastfeeding success and lactation performance in women. However, the mechanisms involved are not entirely understood. In the present study, female C57BL/6 mice were chronically exposed to a high-fat diet to induce obesity and subsequently exhibited impaired offspring viability (only 15% survival rate), milk production (33% reduction), mammopoiesis (one-third of the glandular area compared to control animals) and postpartum maternal behaviors (higher latency to retrieving and grouping the pups). Reproductive experience attenuated these defects. Diet-induced obese mice exhibited high basal pSTAT5 levels in the mammary tissue and hypothalamus, and an acute prolactin stimulus was unable to further increase pSTAT5 levels above basal levels. In contrast, genetically obese leptin-deficient females showed normal prolactin responsiveness. Additionally, we identified the expression of leptin receptors specifically in basal/myoepithelial cells of the mouse mammary gland. Finally, high-fat diet females exhibited altered mRNA levels of ERBB4 and NRG1, suggesting that obesity may involve disturbances to mammary gland paracrine circuits that are critical in the control of luminal progenitor function and lactation. In summary, our findings indicate that high leptin levels are a possible cause of the peripheral and central prolactin resistance observed in obese mice which leads to impaired lactation performance. PMID:26926925

  1. Borrelia burgdorferi strain-specific Osp C-mediated immunity in mice.

    PubMed

    Bockenstedt, L K; Hodzic, E; Feng, S; Bourrel, K W; de Silva, A; Montgomery, R R; Fikrig, E; Radolf, J D; Barthold, S W

    1997-11-01

    Antibodies to the outer surface proteins (Osps) A, B, and C of the spirochete Borrelia burgdorferi can prevent infection in animal models of Lyme borreliosis. We have previously demonstrated that immune serum from mice infected with B. burgdorferi N40 can also prevent challenge infection and induce disease regression in infected mice. The antigens targeted by protective and disease-modulating antibodies are presently unknown, but they do not include Osp A or Osp B. Because Osp C antibodies are present in immune mouse serum, we investigated the ability of hyperimmune serum to recombinant Osp C (N40) to protect mice against challenge infection with N40 spirochetes. In both active and passive immunization studies, Osp C (N40) antiserum failed to protect mice from challenge infection with cultured organisms. Mice actively immunized with recombinant Osp C (N40) were susceptible to tick-borne challenge infection, and nymphal ticks remained infected after feeding on Osp C-hyperimmunized mice. In contrast, similar immunization studies performed with Osp C (PKo) antiserum prevented challenge infection of mice with a clone of PKo spirochetes pathogenic for mice. Both Osp C (N40) and Osp C (PKo) antisera showed minimal in vitro borreliacidal activity, and immunofluorescence studies localized Osp C beneath the outer membrane of both N40 and PKo spirochetes. We conclude that Osp C antibody-mediated immunity is strain specific and propose that differences in Osp C surface expression by spirochetes in vivo may account for strain-specific immunity. PMID:9353047

  2. SENCAR mouse skin tumorigenesis model versus other strains and stocks of mice

    SciTech Connect

    Slaga, T.J.

    1986-09-01

    The SENCAR mouse stock was selectively bred for eight generations for sensitivity to skin tumor induction by the two-stage tumorigenesis protocol using 7,12-dimethylbenz(a)anthracene (DMBA) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The SENCAR mouse was derived by crossing Charles River CD-1 mice with skin-tumor-sensitive mice (STS). The SENCAR mice are much more sensitive to both DMBA tumor initiation and TPA tumor promotion than CD-1, BALB/c, and DBA/2 mice. An even greater difference in the sensitivity to two-stage skin tumorigenesis is apparent between SENCAR and C57BL/6 mice when using DMBA-TPA treatment. However, the SENCAR and C57BL/6 mice have a similar tumor response to DMBA-benzoyl peroxide treatment, suggesting that TPA is not an effective promoter in C57BL/6 mice. The DBA/2 mice respond in a similar manner to the SENCAR mice when using N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-TPA treatment. The SENCAR mouse model provides a good dose-response relationship for many carcinogens used as tumor initiators and for many compounds used as tumor promoter. When compared to other stocks and strains of mice, the SENCAR mouse has one of the largest data bases for carcinogens and promoters.

  3. Insulin Resistance Induces Posttranslational Hepatic Sortilin 1 Degradation in Mice*

    PubMed Central

    Li, Jibiao; Matye, David J.; Li, Tiangang

    2015-01-01

    Insulin promotes hepatic apolipoprotein B100 (apoB100) degradation, whereas insulin resistance is a major cause of hepatic apoB100/triglyceride overproduction in type 2 diabetes. The cellular trafficking receptor sortilin 1 (Sort1) was recently identified to transport apoB100 to the lysosome for degradation in the liver and thus regulate plasma cholesterol and triglyceride levels. Genetic variation of SORT1 was strongly associated with cardiovascular disease risk in humans. The major goal of this study is to investigate the effect and molecular mechanism of insulin regulation of Sort1. Results showed that insulin induced Sort1 protein, but not mRNA, in AML12 cells. Treatment of PI3K or AKT inhibitors decreased Sort1 protein, whereas expression of constitutively active AKT induced Sort1 protein in AML12 cells. Consistently, hepatic Sort1 was down-regulated in diabetic mice, which was partially restored after the administration of the insulin sensitizer metformin. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation. Administration of a PI3K inhibitor to mice decreased hepatic Sort1 protein and increased plasma cholesterol and triglyceride levels. Adenovirus-mediated overexpression of Sort1 in the liver prevented PI3K inhibitor-induced Sort1 down-regulation and decreased plasma triglyceride but had no effect on plasma cholesterol in mice. This study identified Sort1 as a novel target of insulin signaling and suggests that Sort1 may play a role in altered hepatic apoB100 metabolism in insulin-resistant conditions. PMID:25805502

  4. Copper deficiency increases the virulence of amyocarditic and myocarditic strains of coxsackievirus B3 in mice.

    PubMed

    Smith, Allen D; Botero, Sebastian; Levander, Orville A

    2008-05-01

    Deficiency in several trace elements, including copper and selenium, is associated with increased levels of oxidative stress. Copper deficiency also has been shown to impair immune function. Previous work by others demonstrated that passage of an amyocarditic or myocarditic strain of coxsackievirus B3 (CVB3) through selenium- or vitamin E-deficient mice led to increased cardiac pathology. To determine whether a copper deficiency would similarly alter the pathogenesis of CVB3 infections, Swiss outbred dams and their litters were fed copper-deficient diets from birth and received either deionized water or water with 0.315 mmol/L copper as copper sulfate. At 4 wk of age, copper-adequate or -deficient male and female offspring were infected with an amyocarditic or myocarditic strain of CVB3. Heart titers were elevated at d 3 and 7 postinfection in copper-deficient mice infected with the myocarditic CVB3 strain (CVB3/20) but only at d 7 in deficient mice infected with the amyocarditic CVB3 strain (CVB3/0) compared with copper-adequate controls. Copper-deficient mice infected with either strain of CVB3 had increased cardiac pathology compared with copper-adequate controls. Genomic sequences of viruses isolated from copper-adequate and -deficient mice were identical. Heart cytokine expression was elevated in copper-deficient CVB3-infected mice compared with infected controls. Circulating CVB3-specific IgG2a but not IgM levels were decreased in copper-deficient mice. Thus, copper deficiency is associated with an increased inflammatory response but decreased acquired immune response to CVB3 infection that results in increased cardiac pathology, presumably due to increased viral load. PMID:18424590

  5. Banana resistant starch and its effects on constipation model mice.

    PubMed

    Wang, Juan; Huang, Ji Hong; Cheng, Yan Feng; Yang, Gong Ming

    2014-08-01

    Banana resistant starch (BRS) was extracted to investigate the structural properties of BRS, its effects on the gastrointestinal transit, and dejecta of normal and experimentally constipated mice. The mouse constipation model was induced by diphenoxylate administration. The BRS administered mice were divided into three groups and gavaged with 1.0, 2.0, or 4.0 g/kg body weight BRS per day. The small intestinal movement, time of the first black dejecta, dejecta granules, weight and their moisture content, body weight, and food intake of mice were studied. Results showed that the BRS particles were oval and spindly and some light cracks and pits were in the surface. The degree of crystallinity of BRS was 23.13%; the main diffraction peaks were at 2(θ) 15.14, 17.38, 20.08, and 22.51. The degree of polymerization of BRS was 81.16 and the number-average molecular weight was 13147.92 Da, as determined by the reducing terminal method. In animal experiments, BRS at the dose of 4.0 g/kg body weight per day was able to increase the gastrointestinal propulsive rate, and BRS at the doses of 2.0 and 4.0 g/kg body weight per day was found to shorten the start time of defecation by observing the first black dejecta exhaust. However, there were no influences of BRS on the dejecta moisture content, the dejecta granules and their weight, body weight, or daily food intake in mice. BRS was effective in accelerating the movement of the small intestine and in shortening the start time of defecation, but did not impact body weight and food intake. Therefore, BRS had the potential to be useful for improving intestinal motility during constipation. PMID:25046686

  6. The Influence of Visual Ability on Learning and Memory Performance in 13 Strains of Mice

    ERIC Educational Resources Information Center

    Brown, Richard E.; Wong, Aimee A.

    2007-01-01

    We calculated visual ability in 13 strains of mice (129SI/Sv1mJ, A/J, AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, MOLF/EiJ, SJL/J, SM/J, and SPRET/EiJ) on visual detection, pattern discrimination, and visual acuity and tested these and other mice of the same strains in a behavioral test battery that evaluated visuo-spatial…

  7. Emergence of Fluoroquinolone-Resistant Haemophilus influenzae Strains among Elderly Patients but Not among Children▿

    PubMed Central

    Yokota, Shin-ichi; Ohkoshi, Yasuo; Sato, Kiyoshi; Fujii, Nobuhiro

    2008-01-01

    We screened 457 Haemophilus influenzae strains isolated in Japan during 2002 to 2004 and identified 12 fluoroquinolone-resistant strains (2.6%). The resistant strains were divided into three genotypes (eight, three, and one of each type). These were isolated from patients over 58 years of age. Several fluoroquinolone-resistant clones appeared to have invaded the population of elderly patients in a particular area, Sapporo city. PMID:17977993

  8. Alternative genotyping of drug-resistant Mycobacterium tuberculosis strains.

    PubMed

    Antonenko, Petro B; Kresyun, Valentin I; Antonenko, Kate O

    2014-01-01

    The aim of the present research was to study the capability of a genotyping method for M. tuberculosis through detection of six VNTR-loci (MIRU10, MIRU26, MIRU31, MIRU39, MIRU40, ETR-A). Loci MIRU10, MIRU26, MIRU40 and ETR-A have exhibited high polymorphism in group non-Beijing, while loci MIRU26 and MIRU31 - in the Beijing family. A combined detection of all six loci for fingerprinting of the isolates both from Beijing and non-Beijing was highly effective (Hunter-Gaston index was 0.88 and 0.93 correspondently), especially in areas with limited financial resources and high prevalence of multidrug resistant M. tuberculosis strains. PMID:25115121

  9. [Emergence of linezolid-resistant Enterococcus faecalis strains from two inpatients in a pediatric ward].

    PubMed

    Nihonyanagi, Shin; Adachi, Yuzuru; Onuki, Tomoyo; Nakazaki, Nobuhiko; Hirata, Yasuyosi; Fujiki, Kuniko; Takayama, Yoko; Kanoh, Yuhsaku; Bandoh, Yuki; Dantsuji, Yurika; Hanaki, Hideaki; Sunakawa, Keisuke

    2012-09-01

    We report herein on the isolation of three linezolid-resistant Enterococcus faecalis strains in 2011 from two pediatric inpatients at Kitasato University Hospital, Japan. Three linezolid resistant strains were isolated from two patients who shared the same room of a pediatric inpatient ward. Two linezolid resistant strains were isolated from patient A who had been treated with a total of 17,600mg of linezolid during 60 days of hospitalization (strains 1 and 2). The linezolid resistant E. faecalis persisted through the time that the patient had been discharged from the hospital. Another linezolid resistant strain was isolated from patient B who had no history of linezolid administration. The resistant strain in patient B phased out spontaneously. The minimum inhibitory concentration of linezolid in these strains ranged from 8.0 to 16.0 microg/mL. PCR amplification of the chromosomal gene encoding domain V of the 23S rRNA and subsequent nucleotide sequencing revealed that all the strains had at least one G2576T mutation. The pulse-field-gel electrophoretograms of the DNA treated with the SmaI restriction enzyme showed an identical profile suggesting that they were derived from a single resistant strain. These results suggested that the resistant strain occurred in patient A and was transmitted to patient B within the inpatient ward. PMID:23198574

  10. An enterovirus 71 strain causes skeletal muscle damage in infected mice

    PubMed Central

    Lin, Peixin; Gao, Lulu; Huang, Yeen; Chen, Qing; Shen, Hong

    2015-01-01

    Objective: To study the target organs for enterovirus 71 (EV71) in infected suckling mice. Methods: 5-day-old BALB/c suckling mice were infected with an EV71 strain. Tissues of the infected mice were processed for histopathological examination, including immunohistochemistry, in situ hybridization, ultrastructural observation. Results: Some mice developed limb paralysis, trouble walking and loss of balance. Results of the histopathological study showed that a large amount of EV71 existed in the skeletal muscle tissues, accounting for the damage of the skeletal muscles. Conclusion: The EV71 clinical isolate used in this study presented evident myotropism. Skeletal muscles are important target organs for EV71 in the infected suckling mice. To clarify the relationship between EV71 infection and muscle diseases may contribute to a better understanding of the pathogenesis of EV71. PMID:26097530

  11. Early differences in metabolic flexibility between obesity-resistant and obesity-prone mice.

    PubMed

    Bardova, Kristina; Horakova, Olga; Janovska, Petra; Hansikova, Jana; Kus, Vladimir; van Schothorst, Evert M; Hoevenaars, Femke P M; Uil, Melissa; Hensler, Michal; Keijer, Jaap; Kopecky, Jan

    2016-05-01

    Decreased metabolic flexibility, i.e. a compromised ability to adjust fuel oxidation to fuel availability supports development of adverse consequences of obesity. The aims of this study were (i) to learn whether obesity-resistant A/J and obesity-prone C57BL/6J mice differ in their metabolic flexibility right after weaning; and (ii) to characterize possible differences in control of glucose homeostasis in these animals using glucose tolerance tests (GTT). A/J and C57BL/6J mice of both genders were maintained at 20 °C and weaned to standard low-fat diet at 30 days of age. During the first day after weaning, using several separate animal cohorts, (i) GTT was performed using 1 or 3 mg glucose/g body weight (BW), while glucose was administered either orally (OGTT) or intraperitoneally (IPGTT) at 20 °C; and (ii) indirect calorimetry (INCA) was performed, either in a combination with oral gavage of 1 or 7.5 mg glucose/g BW, or during a fasting/re-feeding transition. INCA was conducted either at 20 °C or 34 °C. Results of both OGTT and IPGTT using 1 mg glucose/g BW at 20 °C, and INCA using 7.5 mg glucose/g BW at 34 °C, indicated higher glucose tolerance and higher metabolic flexibility to glucose, respectively, and lower fasting glycemia in A/J mice as compared with C57BL/6J mice. Thus, control of whole body glucose metabolism between A/J and C57BL/6J mice represents a phenotypic feature differentiating between the strains right after weaning. PMID:26607243

  12. Genetic diversity and clonal characteristics of ciprofloxacin-resistant meningococcal strains in China.

    PubMed

    Zhu, Bingqing; Fan, Yaochun; Xu, Zheng; Xu, Li; Du, Pengcheng; Gao, Yuan; Shao, Zhujun

    2014-11-01

    The purpose of the present study was to identify the clonal characteristics and gyrA gene diversity of ciprofloxacin-resistant meningococcal strains in China. One hundred and forty-one ciprofloxacin-resistant and 103 ciprofloxacin-susceptible meningococcal strains were selected for multilocus sequence typing. Of these, 54 ciprofloxacin-resistant and 42 ciprofloxacin-susceptible strains were selected for gyrA gene sequencing. Of the three clonal complexes prevalent in China, serogroup A of ST-5 complex (CC5) and serogroup C/B strains of CC4821 had a high proportion of ciprofloxacin resistance, whereas CC11 serogroup W strains were all susceptible. Nucleotide and amino acid sequences of the gyrA gene among ciprofloxacin-resistant strains showed more diversity than those among ciprofloxacin-susceptible strains. All ciprofloxacin-resistant strains had a T91I mutation and the ciprofloxacin-susceptible strains had no T91I mutation. Phylogenetic analysis showed that the gyrA gene sequences of CC4821 serogroup B/C strains, CC11 serogroup W, CC1 serogroup A, ciprofloxacin-susceptible CC5 serogroup A and reference strains had high similarity. By contrast, the ciprofloxacin-resistant CC5 serogroup A strains had a highly conserved gyrA gene sequence which was different (94.8% similarity) from that in the above strains. The results of our investigation showed that the high proportion of ciprofloxacin resistance in Neisseria meningitidis is associated with certain sequence types (STs) or clonal complexes (CCs). The prevalence of certain CCs with a high proportion of ciprofloxacin resistance can facilitate the spread of ciprofloxacin resistance. PMID:25082942

  13. Resistant starch promotes equol production and inhibits tibial bone loss in ovariectomized mice treated with daidzein.

    PubMed

    Tousen, Yuko; Abe, Fumiko; Ishida, Tatsuya; Uehara, Mariko; Ishimi, Yoshiko

    2011-10-01

    Daidzein is metabolized to equol in the gastrointestinal tract by gut microflora. Equol has greater estrogenic activity than genistein and daidzein, with its production shown to be promoted by dietary fiber. It is known that resistant starch (RS) is not absorbed in the proximal intestine and acts as dietary fiber in the colon. In this study, we investigated the combined effects of daidzein and RS intake on equol production, bone mineral density, and intestinal microflora in ovariectomized (OVX) mice. Female mice of the ddY strain, aged 8 weeks, were either sham operated (n = 6) or OVX. The OVX mice were randomly divided into 5 groups: OVX control (n = 6), OVX fed 0.1% daidzein-supplemented diet (OVX + Dz, n = 8), OVX fed 0.1% daidzein- and 12% RS-supplemented diet (OVX + Dz + RS, n = 8), OVX fed 12% RS-supplemented diet (OVX + RS, n = 8), and OVX who received daily subcutaneous administration of 17 β-estradiol (n = 6). After 6 weeks, urinary equol concentration was significantly higher in the OVX + Dz + RS group than in the OVX + Dz group. The bone mineral density of the whole tibia was higher in the OVX + Dz +RS group compared with the OVX + Dz group. The occupation ratios of Bifidobacterium spp in the cecal microflora in groups fed RS were significantly higher than those in the other groups. The present study demonstrated that RS may increase the bioavailability of daidzein. PMID:21550090

  14. Electrical Properties of Materials for Elevated Temperature Resistance Strain Gage Application. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Lei, Jih-Fen

    1987-01-01

    The objective was to study the electrical resistances of materials that are potentially useful as resistance strain gages at 1000 C. Transition metal carbides and nitrides, boron carbide and silicon carbide were selected for the experimental phase of this research. Due to their low temperature coefficient of resistance and good stability, TiC, ZrC, B sub 4 C and beta-SiC are suggested as good candidates for high temperature resistance strain gage applications.

  15. Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro.

    PubMed

    Gong, Zijian; Lai, Wei; Liu, Min; Hua, Zhengshuang; Sun, Yayin; Xu, Qingfang; Xia, Yue; Zhao, Yue; Xie, Xiaoyuan

    2016-04-01

    The emergence of ceftriaxone-resistantNeisseria gonorrhoeaeis currently a global public health concern. However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance inNeisseria gonorrhoeae, we subcultured six gonococcal strains with increasing concentrations of ceftriaxone and isolated the strains that became resistant. After analyzing several frequently reported genes involved in ceftriaxone resistance, we found only a single mutation inpenA(A501V). However, differential analysis of the genomes and transcriptomes between pre- and postselection strains revealed many other mutated genes as well as up- and downregulated genes. Transformation of the mutatedpenAgene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutatedftsXincreased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, whilepilM,pilN, andpilQwere downregulated. Furthermore, the resistant strain developed cross-resistance to penicillin and cefuroxime, had an increased biochemical metabolic rate, and presented fitness defects such as prolonged growth time and downregulated PilMNQ. In conclusion, antimicrobial pressure could result in the emergence of ceftriaxone resistance, and the evolution of resistance ofNeisseria gonorrhoeaeto ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry. PMID:26787702

  16. Genetic Dependence of Central Corneal Thickness among Inbred Strains of Mice

    PubMed Central

    Lively, Geoffrey D.; Jiang, Bing; Hedberg-Buenz, Adam; Chang, Bo; Petersen, Greg E.; Wang, Kai; Kuehn, Markus H.

    2010-01-01

    Purpose. Central corneal thickness (CCT) exhibits broad variability. For unknown reasons, CCT also associates with diseases not typically considered corneal, particularly glaucoma. The purpose of this study was to test the strain dependence of CCT variability among inbred mice and identify cellular and molecular factors associated with differing CCT. Methods. Methodology for measuring murine CCT with ultrasound pachymetry was developed and used to measure CCT among 17 strains of mice. Corneas from three strains with nonoverlapping differences in CCT (C57BLKS/J, C57BL/6J, and SJL/J) were compared by histology, transmission electron microscopy, and expression profiling with gene microarrays. Results. CCT in mice was highly strain dependent. CCT exhibited continuous variation from 89.2 μm in C57BLKS/J to 123.8 μm in SJL/J. Stromal thickness was the major determinant of the varying murine CCT, with epithelial thickness also contributing. Corneal expression levels of many genes differed between strains with differing CCT, but most of these changes did not correlate with the changes observed in previously studied corneal diseases nor did they correlate with genes encoding major structural proteins of the cornea. Conclusions. Murine CCT has been measured with a variety of different techniques, but only among a limited number of different strains. Here, pachymetry was established as an additional tool and used to conduct a broad survey of different strains of inbred mice. These results demonstrated that murine CCT was highly influenced by genetic background and established a baseline for future genetic approaches to further elucidate mechanisms regulating CCT and its disease associations. PMID:19710407

  17. Reduced uptake and accumulation of norfloxacin in resistant strains of Neisseria gonorrhoeae isolated in Japan.

    PubMed Central

    Tanaka, M; Fukuda, H; Hirai, K; Hosaka, M; Matsumoto, T; Kumazawa, J

    1994-01-01

    OBJECTIVE--To investigate the alteration of cell permeability toward fluoroquinolones in Neisseria gonorrhoeae, which is a major quinolone-resistance mechanism along with the alteration of DNA gyrase in gram-negative bacteria. The prevalence of fluoroquinolone-resistant N gonorrhoeae strains is rapidly increasing in Japan. MATERIALS AND METHODS--The uptake and accumulation of norfloxacin by gonococcal cells, including six clinical and five World Health Organization (WHO) reference strains, were measured. Of the six clinical strains, two were highly resistant to norfloxacin (MIC 8.0 and 4.0 micrograms/ml), two were moderately resistant (MIC 1.0 and 0.5 microgram/ml), and two were sensitive (MIC 0.063 and 0.004 microgram/ml). All five WHO reference strains were sensitive to norfloxacin (MIC < or = 0.001 to 0.063 microgram/ml). RESULTS--Mean initial norfloxacin uptake in the four resistant strains (104 ng/mg of dry cells) was significantly lower than that in the seven sensitive strains (158 ng/mg of dry cells) (p < 0.05). The mean uptake after 20 minutes was also significantly lower in the four resistant strains (130 ng/mg of dry cells) than in the seven sensitive strains (194 ng/mg of dry cells) (p < 0.05). However, there was no significant difference in mean norfloxacin accumulation after 20 minutes between the four resistant strains (26 ng/mg of dry cells) and the seven sensitive strains (36 ng/mg of dry cells). The accumulation of norfloxacin after 20 minutes was almost zero in two of the four resistant strains, while the remaining two strains accumulated norfloxacin as well as the sensitive strains. CONCLUSIONS--These findings suggest that alteration of bacterial cell permeability is a quinolone-resistance mechanism in N gonorrhoeae isolated in Japan, and that this bacteria may exhibit other mechanisms such as alteration of DNA gyrase. PMID:7959709

  18. Persistence of antibiotic resistance: evaluation of a probiotic approach using antibiotic-sensitive Megasphaera elsdenii strains to prevent colonization of swine by antibiotic-resistant strains.

    PubMed

    Stanton, Thad B; Humphrey, Samuel B

    2011-10-01

    Megasphaera elsdenii is a lactate-fermenting, obligately anaerobic bacterium commonly present in the gastrointestinal tracts of mammals, including humans. Swine M. elsdenii strains were previously shown to have high levels of tetracycline resistance (MIC=64 to >256 μg/ml) and to carry mosaic (recombinant) tetracycline resistance genes. Baby pigs inherit intestinal microbiota from the mother sow. In these investigations we addressed two questions. When do M. elsdenii strains from the sow colonize baby pigs? Can five antibiotic-sensitive M. elsdenii strains administered intragastrically to newborn pigs affect natural colonization of the piglets by antibiotic-resistant (AR) M. elsdenii strains from the mother? M. elsdenii natural colonization of newborn pigs was undetectable (<10(4) CFU/g [wet weight] of feces) prior to weaning (20 days after birth). After weaning, all pigs became colonized (4 × 10(5) to 2 × 10(8) CFU/g feces). In a separate study, 61% (76/125) of M. elsdenii isolates from a gravid sow never exposed to antibiotics were resistant to chlortetracycline, ampicillin, or tylosin. The inoculation of the sow's offspring with mixtures of M. elsdenii antibiotic-sensitive strains prevented colonization of the offspring by maternal AR strains until at least 11 days postweaning. At 25 and 53 days postweaning, however, AR strains predominated. Antibiotic susceptibility phenotypes and single nucleotide polymorphism (SNP)-based identities of M. elsdenii isolated from sow and offspring were unexpectedly diverse. These results suggest that dosing newborn piglets with M. elsdenii antibiotic-sensitive strains delays but does not prevent colonization by maternal resistant strains. M. elsdenii subspecies diversity offers an explanation for the persistence of resistant strains in the absence of antibiotic selection. PMID:21821757

  19. A Conformationally Constrained Cyclic Acyldepsipeptide Is Highly Effective in Mice Infected with Methicillin-Susceptible and -Resistant Staphylococcus aureus

    PubMed Central

    Arvanitis, Marios; Li, Gang; Li, De-Dong; Cotnoir, Daniel; Ganley-Leal, Lisa; Carney, Daniel W.; Sello, Jason K.; Mylonakis, Eleftherios

    2016-01-01

    Background Cyclic acyldepsipeptides (ADEPs) are a novel class of antibacterial agents, some of which (e.g., ADEP 4) are highly active against Gram-positive bacteria. The focus of these in vivo studies is ADEP B315, a rationally designed compound that has the most potent in vitro activity of any ADEP analog reported to date. Methods In vivo efficacy experiments were performed using lethal intraperitoneal mice infection models with a methicillin-sensitive S. aureus (MSSA) and a methicillin-resistant (MRSA) strain. The infected mice were treated with ADEP B315, a des-methyl analog of ADEP 4, vancomycin, or the vehicle used for the ADEPs and their survival was assessed daily. A subset of MSSA-infected mice was sacrificed soon after inoculation and the bacterial burden was measured in their livers and spleens. The toxicity of ADEP B315 was assessed in viability assays using human whole blood cultures. Results In the MSSA experiments, all mice treated with the vehicle succumbed to the infection within 24 hours. All tested compounds were effective in prolonging survival of infected mice (p<0.001). Mice treated with ADEP B315 had a 39% survival rate by 10 days compared to 7% survival in mice treated with a des-methyl ADEP 4 analog (p = 0.017). Survival of the infected mice treated with ADEP B315 was comparable to those treated with vanocmycin (p = 0.12) at the same dose. Further, bacterial burden in the liver and spleen was significantly lower in mice treated with ADEP B315 compared to controls. In the MRSA experiments, ADEP B315 was able to significantly prolong survival compared to mice treated with either the vehicle (p = 0.001) or vancomycin (p = 0.007). ADEP B315 exhibited no significant toxicity in human whole blood cultures at concentrations up to 25 μg/ml. Conclusions ADEP B315 is safe and can cure mice that have lethal infections of methicillin-sensitive and -resistant strains of S. aureus. PMID:27101010

  20. Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition.

    PubMed

    Schwarzer, Martin; Makki, Kassem; Storelli, Gilles; Machuca-Gayet, Irma; Srutkova, Dagmar; Hermanova, Petra; Martino, Maria Elena; Balmand, Severine; Hudcovic, Tomas; Heddi, Abdelaziz; Rieusset, Jennifer; Kozakova, Hana; Vidal, Hubert; Leulier, François

    2016-02-19

    In most animal species, juvenile growth is marked by an exponential gain in body weight and size. Here we show that the microbiota of infant mice sustains both weight gain and longitudinal growth when mice are fed a standard laboratory mouse diet or a nutritionally depleted diet. We found that the intestinal microbiota interacts with the somatotropic hormone axis to drive systemic growth. Using monocolonized mouse models, we showed that selected lactobacilli promoted juvenile growth in a strain-dependent manner that recapitulated the microbiota's effect on growth and the somatotropic axis. These findings show that the host's microbiota supports juvenile growth. Moreover, we discovered that lactobacilli strains buffered the adverse effects of chronic undernutrition on the postnatal growth of germ-free mice. PMID:26912894

  1. Gender and strain contributions to the variability of buprenorphine-related respiratory toxicity in mice.

    PubMed

    Alhaddad, Hisham; Cisternino, Salvatore; Saubamea, Bruno; Schlatter, Joel; Chiadmi, Fouad; Risède, Patricia; Smirnova, Maria; Cochois-Guégan, Véronique; Tournier, Nicolas; Baud, Frédéric J; Mégarbane, Bruno

    2013-03-01

    While most deaths from asphyxia related to buprenorphine (BUP) overdose have been reported in males, higher plasma concentrations of BUP and its toxic metabolite norbuprenorphine (NBUP) have been observed in females. We previously demonstrated that P-glycoprotein (P-gp) modulation at the blood-brain barrier (BBB) contributes highly to BUP-related respiratory toxicity, by limiting NBUP entrance into the brain. In this work, we sought to investigate the role of P-gp-mediated transport at the BBB in gender and strain-related variability of BUP and NBUP-induced respiratory effects in mice. Ventilation was studied using plethysmography, P-gp expression using western blot, and transport at the BBB using in situ cerebral perfusion. In male Fvb and Swiss mice, BUP was responsible for ceiling respiratory effects. NBUP-related reduction in minute volume was dose-dependent but more marked in Fvb (p<0.01 at 1mg/kg NBUP and p<0.001 at 3 and 9mg/kg NBUP) than in Swiss mice (p<0.001 at 9mg/kg NBUP). Female Fvb mice were more susceptible to BUP than males with significantly increased inspiratory time (p<0.05) and to NBUP with significantly increased expiratory time (p<0.01). Following BUP administration, plasma BUP concentrations were significantly higher (p<0.01) and plasma NBUP concentrations significantly lower (p<0.001) in Fvb mice compared to Swiss mice. Plasma BUP concentrations were significantly higher (p<0.05) and plasma NBUP concentrations significantly lower (p<0.01) in male compared to female Fvb mice. In contrast, following NBUP administration, comparable plasma NBUP concentrations were observed in both genders and strains. No differences in P-gp expression or BUP and NBUP transport across the BBB were observed between male and female Fvb mice as well as between Swiss and Fvb mice. Our results suggest that P-gp-mediated transport across the BBB does not play a key-role in gender and strain-related variability in BUP and NBUP-induced respiratory toxicity in mice. Both

  2. The genetic architecture of NAFLD among inbred strains of mice

    PubMed Central

    Hui, Simon T; Parks, Brian W; Org, Elin; Norheim, Frode; Che, Nam; Pan, Calvin; Castellani, Lawrence W; Charugundla, Sarada; Dirks, Darwin L; Psychogios, Nikolaos; Neuhaus, Isaac; Gerszten, Robert E; Kirchgessner, Todd; Gargalovic, Peter S; Lusis, Aldons J

    2015-01-01

    To identify genetic and environmental factors contributing to the pathogenesis of non-alcoholic fatty liver disease, we examined liver steatosis and related clinical and molecular traits in more than 100 unique inbred mouse strains, which were fed a diet rich in fat and carbohydrates. A >30-fold variation in hepatic TG accumulation was observed among the strains. Genome-wide association studies revealed three loci associated with hepatic TG accumulation. Utilizing transcriptomic data from the liver and adipose tissue, we identified several high-confidence candidate genes for hepatic steatosis, including Gde1, a glycerophosphodiester phosphodiesterase not previously implicated in triglyceride metabolism. We confirmed the role of Gde1 by in vivo hepatic over-expression and shRNA knockdown studies. We hypothesize that Gde1 expression increases TG production by contributing to the production of glycerol-3-phosphate. Our multi-level data, including transcript levels, metabolite levels, and gut microbiota composition, provide a framework for understanding genetic and environmental interactions underlying hepatic steatosis. DOI: http://dx.doi.org/10.7554/eLife.05607.001 PMID:26067236

  3. Learning Strategy Selection in the Water Maze and Hippocampal CREB Phosphorylation Differ in Two Inbred Strains of Mice

    ERIC Educational Resources Information Center

    Sung, Jin-Young; Goo, June-Seo; Lee, Dong-Eun; Jin, Da-Qing; Bizon, Jennifer L.; Gallagher, Michela; Han, Jung-Soo

    2008-01-01

    Learning strategy selection was assessed in two different inbred strains of mice, C57BL/6 and DBA/2, which are used for developing genetically modified mouse models. Male mice received a training protocol in a water maze using alternating blocks of visible and hidden platform trials, during which mice escaped to a single location. After training,…

  4. The effect of tensile hysteresis and contact resistance on the performance of strain-resistant elastic-conductive webbing.

    PubMed

    Shyr, Tien-Wei; Shie, Jing-Wen; Jhuang, Yan-Er

    2011-01-01

    To use e-textiles as a strain-resistance sensor they need to be both elastic and conductive. Three kinds of elastic-conductive webbings, including flat, tubular, and belt webbings, made of Lycra fiber and carbon coated polyamide fiber, were used in this study. The strain-resistance properties of the webbings were evaluated in stretch-recovery tests and measured within 30% strain. It was found that tensile hysteresis and contact resistance significantly influence the tensile elasticity and the resistance sensitivity of the webbings. The results showed that the webbing structure definitely contributes to the tensile hysteresis and contact resistance. The smaller the friction is among the yarns in the belt webbing, the smaller the tensile hysteresis loss. However the close proximity of the conductive yarns in flat and tubular webbings results in a lower contact resistance. PMID:22319376

  5. The Effect of Tensile Hysteresis and Contact Resistance on the Performance of Strain-Resistant Elastic-Conductive Webbing

    PubMed Central

    Shyr, Tien-Wei; Shie, Jing-Wen; Jhuang, Yan-Er

    2011-01-01

    To use e-textiles as a strain-resistance sensor they need to be both elastic and conductive. Three kinds of elastic-conductive webbings, including flat, tubular, and belt webbings, made of Lycra fiber and carbon coated polyamide fiber, were used in this study. The strain-resistance properties of the webbings were evaluated in stretch-recovery tests and measured within 30% strain. It was found that tensile hysteresis and contact resistance significantly influence the tensile elasticity and the resistance sensitivity of the webbings. The results showed that the webbing structure definitely contributes to the tensile hysteresis and contact resistance. The smaller the friction is among the yarns in the belt webbing, the smaller the tensile hysteresis loss. However the close proximity of the conductive yarns in flat and tubular webbings results in a lower contact resistance. PMID:22319376

  6. Intra-strain polymorphisms are detected but no genomic alteration is found in cloned mice

    SciTech Connect

    Gotoh, Koshichi . E-mail: koshichi@kazusa.or.jp; Inoue, Kimiko; Ogura, Atsuo; Oishi, Michio

    2006-09-15

    In-gel competitive reassociation (IGCR) is a method for differential subtraction of polymorphic (RFLP) DNA fragments between two DNA samples of interest without probes or specific sequence information. Here, we applied the IGCR procedure to two cloned mice derived from an F1 hybrid of the C57BL/6Cr and DBA/2 strains, in order to investigate the possibility of genomic alteration in the cloned mouse genomes. Each of the five of the genomic alterations we detected between the two cloned mice corresponded to the 'intra-strain' polymorphisms in the C57BL/6Cr and DBA/2 mouse strains. Our result suggests that no severe aberration of genome sequences occurs due to somatic cell nuclear transfer.

  7. Probiotic Pediococcus pentosaceus strain GS4 alleviates azoxymethane-induced toxicity in mice.

    PubMed

    Dubey, Vinay; Ghosh, Asit R; Bishayee, Kausik; Khuda-Bukhsh, Anisur R

    2015-10-01

    Probiotic treatment has been gaining attention due to its remarkable effects in alleviating toxicity and carcinogenesis. The novel strain Pediococcus pentosaceus GS4 has been reported for probiotic, survivability in simulated gastrointestinal fluid, and antioxidative and biohydrogenation properties. Therefore, we hypothesize that this specific strain might be able to assuage the effect of azoxymethane (AOM)-induced toxicity in mice. Twenty-eight Swiss albino mice were divided into 4 groups and were studied for 32 weeks. Azoxymethane (10 mg/kg body weight) was administered intraperitoneally twice (0th and 14th days), and probiotic GS4 (1.1 × 10(9) colony-forming unit/mL) was given orally for the respective groups. Mice who served as the normal control received only normal saline. GS4-intervened AOM-induced mice showed marked improvement at the histopathologic level, in the liver and kidney. Moreover, probiotic GS4 intervention in AOM-induced mice exhibited a significant reduction in the liver function biomarker when compared with the AOM-induced mice. Probiotic GS4 intervention reduced the intestinal structural deformities as evident from the elevated brush border membrane-associated disaccharidases (sucrase, lactase) and intestinal alkaline phosphatase activities, which were found disrupted by AOM intoxication. Fecal bacterial load was found to be reduced in AOM-induced mice which were subsequently replenished by the probiotic GS4 intervention as apparent from the enhanced fecal bacterial load. There were no adverse effects observed in the probiotic control group. Conclusively, novel probiotic strain GS4 exhibited safe and beneficial effects against the toxicity threats posed by AOM. Thus, GS4 could be considered as a potential food supplement/additive for therapeutic purposes in gastrointestinal disorders related to inflammation and cancer. PMID:26319614

  8. Strain commonalities and differences in response-outcome decision making in mice.

    PubMed

    Zimmermann, Kelsey S; Hsu, Chia-Chun; Gourley, Shannon L

    2016-05-01

    The ability to select between actions that are more vs. less likely to be reinforced is necessary for survival and navigation of a changing environment. A task termed "response-outcome contingency degradation" can be used in the laboratory to determine whether rodents behave according to such goal-directed response strategies. In one iteration of this task, rodents are trained to perform two food-reinforced behaviors, then the predictive relationship between one instrumental response and the associated outcome is modified by providing the reinforcer associated with that response non-contingently. During a subsequent probe test, animals can select between the two trained responses. Preferential engagement of the behavior most likely to be reinforced is considered goal-directed, while non-selective responding is considered a failure in response-outcome conditioning, or "habitual." This test has largely been used with rats, and less so with mice. Here we compiled data collected from several cohorts of mice tested in our lab between 2012 and 2015. Mice were bred on either a C57BL/6 or predominantly BALB/c strain background. We report that both strains of mice can use information acquired as a result of instrumental contingency degradation training to select amongst multiple response options the response most likely to be reinforced. Mice differ, however, during the training sessions when the familiar response-outcome contingency is being violated. BALB/c mice readily generate perseverative or habit-like response strategies when the only available response is unlikely to be reinforced, while C57BL/6 mice more readily inhibit responding. These findings provide evidence of strain differences in response strategies when an anticipated reinforcer is unlikely to be delivered. PMID:27003118

  9. Finished Annotated Genome Sequence of Burkholderia pseudomallei Strain Bp1651, a Multidrug-Resistant Clinical Isolate

    PubMed Central

    Sue, David; Hakovirta, Janetta; Loparev, Vladimir N.; Knipe, Kristen; Sammons, Scott A.; Ranganathan-Ganakammal, Satishkumar; Changayil, Shankar; Srinivasamoorthy, Ganesh; Weil, Michael R.; Tatusov, Roman L.; Gee, Jay E.; Elrod, Mindy G.; Hoffmaster, Alex R.; Weigel, Linda M.

    2015-01-01

    Burkholderia pseudomallei strain Bp1651, a human isolate, is resistant to all clinically relevant antibiotics. We report here on the finished genome sequence assembly and annotation of the two chromosomes of this strain. This genome sequence may assist in understanding the mechanisms of antimicrobial resistance for this pathogenic species. PMID:26634765

  10. Variability in empathic fear response among 11 inbred strains of mice.

    PubMed

    Keum, S; Park, J; Kim, A; Park, J; Kim, K K; Jeong, J; Shin, H-S

    2016-02-01

    Empathy is an important emotional process that involves the ability to recognize and share emotions with others. We have previously developed an observational fear learning (OFL) behavioral assay to measure empathic fear in mice. In the OFL task, a mouse is conditioned for context-dependent fear when it observes a conspecific demonstrator receiving aversive stimuli. In the present study, by comparing 11 different inbred mouse strains that are commonly used in the laboratory, we found that empathic fear response was highly variable between different strains. Five strains--C57BL/6J, C57BL/6NTac, 129S1/SvImJ, 129S4/SvJae and BTBR T(+) Itpr3(tf) /J--showed observational fear (OF) responses, whereas AKR/J, BALB/cByJ, C3H/HeJ, DBA/2J, FVB/NJ and NOD/ShiLtJ mice exhibited low empathic fear response. Importantly, day 2 OF memory was significantly correlated with contextual memory in the classical fear conditioning among the 11 strains. Innate differences in anxiety, locomotor activity, sociability and preference for social novelty were not significantly correlated with OFL. Interestingly, early adolescent C57BL/6J mice exhibited an increase in acquisition of OF. The level of OFL in C57BL/6J strain was not affected by sex or strains of the demonstrator. Taken together, these data strongly suggest that there are naturally occurring OFL-specific genetic variations modulating empathic fear behaviors in mice. The identification of causal genes may uncover novel genetic pathways and underlying neural mechanisms that modulate empathic fear and, ultimately, provide new targets for therapeutic intervention in human mental disorders associated with impaired empathy. PMID:26690560

  11. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    SciTech Connect

    Kimura, Akihiko; Ishida, Yuko; Wada, Takashi; Yokoyama, Hitoshi; Mukaida, Naofumi; Kondo, Toshikazu . E-mail: kondot@wakayama-med.ac.jp

    2005-02-15

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs.

  12. Resistance Pattern and Molecular Characterization of Enterotoxigenic Escherichia coli (ETEC) Strains Isolated in Bangladesh

    PubMed Central

    Begum, Yasmin A.; Talukder, K. A.; Azmi, Ishrat J.; Shahnaij, Mohammad; Sheikh, A.; Sharmin, Salma; Svennerholm, A.-M.; Qadri, Firdausi

    2016-01-01

    Background Enterotoxigenic Escherichia coli (ETEC) is a common cause of bacterial infection leading to acute watery diarrhea in infants and young children as well as in travellers to ETEC endemic countries. Ciprofloxacin is a broad-spectrum antimicrobial agent nowadays used for the treatment of diarrhea. This study aimed to characterize ciprofloxacin resistant ETEC strains isolated from diarrheal patients in Bangladesh. Methods A total of 8580 stool specimens from diarrheal patients attending the icddr,b Dhaka hospital was screened for ETEC between 2005 and 2009. PCR and Ganglioside GM1- Enzyme Linked Immuno sorbent Assay (ELISA) was used for detection of Heat labile (LT) and Heat stable (ST) toxins of ETEC. Antimicrobial susceptibilities for commonly used antibiotics and the minimum inhibitory concentration (MIC) of nalidixic acid, ciprofloxacin and azithromycin were examined. DNA sequencing of representative ciprofloxacin resistant strains was performed to analyze mutations of the quinolone resistance-determining region of gyrA, gyrB, parC and parE. PCR was used for the detection of qnr, a plasmid mediated ciprofloxacin resistance gene. Clonal variations among ciprofloxacin resistant (CipR) and ciprofloxacin susceptible (CipS) strains were determined by Pulsed-field gel electrophoresis (PFGE). Results Among 1067 (12%) ETEC isolates identified, 42% produced LT/ST, 28% ST and 30% LT alone. Forty nine percent (n = 523) of the ETEC strains expressed one or more of the 13 tested colonization factors (CFs) as determined by dot blot immunoassay. Antibiotic resistance of the ETEC strains was observed as follows: ampicillin 66%, azithromycin 27%, ciprofloxacin 27%, ceftriazone 13%, cotrimaxazole 46%, doxycycline 44%, erythromycin 96%, nalidixic acid 83%, norfloxacin 27%, streptomycin 48% and tetracycline 42%. Resistance to ciprofloxacin increased from 13% in 2005 to 34% in 2009. None of the strains was resistant to mecillinam. The MIC of the nalidixic acid and

  13. Antibiotic sensitivity of Haemophilus influenzae strains including three recent chloramphenicol-resistant isolates.

    PubMed

    Zackrisson, G; Brorson, J E

    1980-08-01

    The antibiotic sensitivity of 100 recent isolates of Haemophilus influenzae was determined. Three strains were resistant to chloramphenicol with minimal inhibitory concentrations of 16 microgram/ml. Of these three resistant strains, one produced betalactamase and one was resistant to sulfamethoxazole-trimethoprim. The remaining strains were inhibited by 0.25-2.0 microgram/ml of chloramphenicol. Ampicillin and benzylpenicillin were found to inhibit all but the betalactamase-producing strains at low concentrations. Regarding sulfamethoxazole-trimethoprim 96% had minimal inhibitory concentrations of 2.5-0.12 microgram/ml or less, while two strains were resistant. The invitro efficacy of erythromycin against H. influenzae was low. The majority of the strains was inhibited by low concentrations of doxycycline and cefuroxime while cefoxitin exhibited minimal inhibitory concentrations values usually exceeding 1 microgram/ml. The minimal inhibitory concentrations registered are compared to the concentrations of the different antibiotics attainable in certain body fluids. PMID:6968146

  14. Inheritance of DDT-resistance in a European strain of Blattella germanica (L.).

    PubMed

    COCHRAN, D G; ROSS, M H

    1962-01-01

    A strain of Blattella germanica has recently been obtained from Europe which has proved to be highly resistant to DDT. This paper reports on genetical studies designed to show the mechanism of inheritance of the trait. Various crosses involving this strain and strains susceptible to DDT or possessing genetic markers were made. Progeny were tested for resistance to DDT and were examined for markers. The results show that DDT resistance is inherited as a simple Mendelian trait, with the hybrid being incompletely susceptible. Resistance appears to be on the same linkage group as "balloon-wing", but is independent of "orange-body". PMID:14021877

  15. Insect growth regulators: I. Biological activity of some IGR's against the susceptible and resistant strains of Culex pipiens larvae. II. Pattern of cross resistance to IGR's in carbaryl-resistant strain.

    PubMed

    Bakr, R F; Abo Gabal, N M; Hussein, M A

    1989-12-01

    The biological activity and cross-resistance of some IGR's, Dimilin, BAY SIR 8514 and Chlorofluzuron against susceptible and carbaryl-resistant strains of Culex pipiens were determined. The results indicated that these compounds are highly effective against the larvae of C. pipiens but more potent larvicides against the susceptible larvae than against the resistant ones. The pattern of cross-resistance to the used IGR's in the carbaryl-resistant strain were obtained. The data revealed no three IGR's as larvicides against the susceptible and resistant Culex pipiens. The pattern of cross resistance to other potent IGR's was also studies. PMID:2504825

  16. Experimental Induction of Paromomycin Resistance in Antimony-Resistant Strains of L. donovani: Outcome Dependent on In Vitro Selection Protocol

    PubMed Central

    Bhandari, Vasundhra; Kuypers, Kristel; Shaw, Craig D.; Lonchamp, Julien; Salotra, Poonam; Carter, Katharine; Sundar, Shyam; Rijal, Suman; Dujardin, Jean-Claude; Cos, Paul; Maes, Louis

    2012-01-01

    Paromomycin (PMM) has recently been introduced for treatment of visceral leishmaniasis in India. Although no clinical resistance has yet been reported, proactive vigilance should be warranted. The present in vitro study compared the outcome and stability of experimental PMM-resistance induction on promastigotes and intracellular amastigotes. Cloned antimony-resistant L. donovani field isolates from India and Nepal were exposed to stepwise increasing concentrations of PMM (up to 500 µM), either as promastigotes or intracellular amastigotes. One resulting resistant strain was cloned and checked for stability of resistance by drug-free in vitro passage as promastigotes for 20 weeks or a single in vivo passage in the golden hamster. Resistance selection in promastigotes took about 25 weeks to reach the maximal 97 µM inclusion level that did not affect normal growth. Comparison of the IC50 values between the parent and the selected strains revealed a 9 to 11-fold resistance for the Indian and 3 to 5-fold for the Nepalese strains whereby the resistant phenotype was also maintained at the level of the amastigote. Applying PMM pressure to intracellular amastigotes produced resistance after just two selection cycles (IC50 = 199 µM) compared to the parent strain (IC50 = 45 µM). In the amastigote-induced strains/clones, lower PMM susceptibilities were seen only in amastigotes and not at all in promastigotes. This resistance phenotype remained stable after serial in vitro passage as promastigote for 20 weeks and after a single in vivo passage in the hamster. This study clearly demonstrates that a different PMM-resistance phenotype is obtained whether drug selection is applied to promastigotes or intracellular amastigotes. These findings may have important relevance to resistance mechanism investigations and the likelihood of resistance development and detection in the field. PMID:22666513

  17. Comparative Genomics of Environmental and Clinical Stenotrophomonas maltophilia Strains with Different Antibiotic Resistance Profiles.

    PubMed

    Youenou, Benjamin; Favre-Bonté, Sabine; Bodilis, Josselin; Brothier, Elisabeth; Dubost, Audrey; Muller, Daniel; Nazaret, Sylvie

    2015-09-01

    Stenotrophomonas maltophilia, a ubiquitous Gram-negative γ-proteobacterium, has emerged as an important opportunistic pathogen responsible for nosocomial infections. A major characteristic of clinical isolates is their high intrinsic or acquired antibiotic resistance level. The aim of this study was to decipher the genetic determinism of antibiotic resistance among strains from different origins (i.e., natural environment and clinical origin) showing various antibiotic resistance profiles. To this purpose, we selected three strains isolated from soil collected in France or Burkina Faso that showed contrasting antibiotic resistance profiles. After whole-genome sequencing, the phylogenetic relationships of these 3 strains and 11 strains with available genome sequences were determined. Results showed that a strain's phylogeny did not match their origin or antibiotic resistance profiles. Numerous antibiotic resistance coding genes and efflux pump operons were revealed by the genome analysis, with 57% of the identified genes not previously described. No major variation in the antibiotic resistance gene content was observed between strains irrespective of their origin and antibiotic resistance profiles. Although environmental strains generally carry as many multidrug resistant (MDR) efflux pumps as clinical strains, the absence of resistance-nodulation-division (RND) pumps (i.e., SmeABC) previously described to be specific to S. maltophilia was revealed in two environmental strains (BurA1 and PierC1). Furthermore the genome analysis of the environmental MDR strain BurA1 showed the absence of SmeABC but the presence of another putative MDR RND efflux pump, named EbyCAB on a genomic island probably acquired through horizontal gene transfer. PMID:26276674

  18. Resistance to antimicrobial agents of Campylobacter spp. strains isolated from animals in Poland.

    PubMed

    Krutkiewicz, A; Sałamaszyńska-Guz, A; Rzewuska, M; Klimuszko, D; Binek, M

    2009-01-01

    A total of 69 Campylobacter jejuni and 16 Campylobacter coli strains isolated from chicken, dog and pig stool samples were characterized based on their resistance to five antimicrobial agents and on plasmid pTet profiles. Antimicrobials used in this study were: amoxicillin/clavulanic acid, ciprofloxacin, erythromycin, tetracycline and trimethoprim/sulfamethoxazole. Among the isolates studied, 91.7% were resistant to one or more antimicrobial agent. The highest level of resistance for the whole test group was to trimethoprim/sulfamethoxazole (57.6%), followed by ciprofloxacin (44.2%) and tetracycline (20%). All isolates were susceptible to amoxicillin/clavulanic acid. Strains isolated from chickens were susceptible to erythromycin. Few erythromycin-resistant strains were isolated from dogs and pigs (5.8%). C. coli strains exhibited a higher antibiotic resistance than C. jejuni strains, excluding resistance to trimethoprim/sulfamethoxazole. The pTet plasmid harboring the tet(O) gene was detected in 14 Campylobacter spp. strains. Our studies demonstrate that the majority (71.4%) of tetracycline-resistant isolates carry a plasmid-borne tet(O) gene, particularly strains for which the minimum inhibitory concentration (MIC) are > or = 256 microg/ml. In conclusion, we have found high-level trimethoprim/sulfamethoxazole, ciprofloxacin and tetracycline resistance in Polish strains isolated from different sources. This study has demonstrated that resistance of Campylobacter species differs depending on both the bacterial species and animal origins. All strains that displayed resistance to four antimicrobial agents were isolated from pigs. Localization of the tet(O) gene on either plasmid or chromosome was not found to be correlated with tetracycline resistance. PMID:20169919

  19. Over-expression of CYP6A2 is associated with spirotetramat resistance and cross-resistance in the resistant strain of Aphis gossypii Glover.

    PubMed

    Peng, Tianfei; Pan, Yiou; Yang, Chen; Gao, Xiwu; Xi, Jinghui; Wu, Yongqiang; Huang, Xiao; Zhu, E; Xin, Xuecheng; Zhan, Chao; Shang, Qingli

    2016-01-01

    A laboratory-selected spirotetramat-resistant strain (SR) of cotton aphid developed 579-fold and 15-fold resistance to spirotetramat in adult aphids and 3rd instar nymphs, respectively, compared with a susceptible strain (SS) [26]. The SR strain developed high-level cross-resistance to alpha-cypermethrin and bifenthrin and very low or no cross-resistance to the other tested insecticides. Synergist piperonyl butoxide (PBO) dramatically increased the toxicity of spirotetramat and alpha-cypermethrin in the resistant strain. RT-qPCR results demonstrated that the transcriptional levels of CYP6A2 increased significantly in the SR strain compared with the SS strain, which was consistent with the transcriptome results [30]. The depletion of CYP6A2 transcripts by RNAi also significantly increased the sensitivity of the resistant aphid to spirotetramat and alpha-cypermethrin. These results indicate the possible involvement of CYP6A2 in spirotetramat resistance and alpha-cypermethrin cross-resistance in the cotton aphid. These together with other cross-resistance results have implications for the successful implementation of resistance management strategies for Aphis gossypii. PMID:26778436

  20. Streptococcus anginosus (milleri) Group Strains Isolated in Poland (1996-2012) and their Antibiotic Resistance Patterns.

    PubMed

    Obszańska, Katarzyna; Kern-Zdanowicz, Izabella; Kozińska, Aleksandra; Machura, Katarzyna; Stefaniuk, Elzbieta; Hryniewicz, Waleria; Sitkiewicz, Izabela

    2016-01-01

    Streptococcus anginosus, Streptococcus intermedius and Streptococcus constellatus form a group of related streptococcal species, namely the Streptococcus Anginosus Group (SAG). The group, previously called "milleri" had been rarely described until 1980/1990 as source of infections. Nowadays SAG bacteria are often described as pathogens causing predominantly purulent infections. The number of infections is highly underestimated, as SAG strains are often classified in the microbiology laboratory as less virulent "viridans streptococci" Epidemiological situation regarding SAG infections in Poland has been unrecognized, therefore we performed a retrospective analysis of strains isolated between 1996 and 2012. Strains suspected of belonging to SAG were re-identified using an automated biochemical approach (Vitek2) and MALDI-TOF MS. We performed first analysis of antibiotic resistance among SAG strains isolated in Poland using automated methods (Vitek2), disk diffusion tests and E-Tests. We also performed PCR detection of resistance determinants in antibiotic resistant strains. Clonal structure of analyzed strains was evaluated with PFGE and MLVF methods. All three species are difficult to distinguish using automated diagnostic methods and the same is true for automated MIC evaluation. Our analysis revealed SAG strains are rarely isolated in Poland, predominantly from purulent infections. All isolates are very diverse on the genomic level as estimated by PFGE and MLVF analyses. All analyzed strains are sensitive to penicillin, a substantial group of strains is resistant to macrolides and the majority of strains are resistant to tetracycline. PMID:27281992

  1. Molecular and virulence characteristics of multi-drug resistant Salmonella Enteritidis strains isolated from poultry.

    PubMed

    Hur, Jin; Kim, Ji Hee; Park, Jong Ho; Lee, Young-Ju; Lee, John Hwa

    2011-09-01

    Forty-six Salmonella enterica subspecies enterica serovar Enteritidis (S. Enteritidis) strains were isolated from chicken meat, faeces, and eggshells collected from hatcheries throughout Korea. The strains were examined for the presence of antimicrobial resistance and virulence genes. All 46 isolates were resistant to at least one of 21 antibiotics used in this study, 30 (65.2%) were resistant to three or more antimicrobials, and a single remarkable isolate was resistant to 15 antimicrobials. The isolates were primarily resistant to penicillins, sulfisoxazole, streptomycin, tetracycline and quinolones. The high rate of resistance in S. Enteritidis strains, sometimes to multiple drugs, may complicate future options for treating human infections. Nineteen of the 21 penicillin resistant isolates carried the bla(TEM) gene, while one strain, resistant both to penicillins and ceftriaxone, carried the bla(CTX-M) gene. Thirty-seven of the 45 sulfisoxazole resistant isolates carried sul2, and 23/24 streptomycin resistant isolates carried both strA and strB. All 10 tetracycline resistant isolates carried the tet(A) gene. Most isolates harboured both SPI-1 and SPI-2-associated genes, and the spv operon, which are known to be associated with human infections. The presence of these genes suggests that these strains could give rise to public health problems if dispersed in the general human population. PMID:20822940

  2. Re-infection of the prion from the scrapie-infected cell line SMB-S15 in three strains of mice, CD1, C57BL/6 and Balb/c

    PubMed Central

    XIAO, KANG; ZHANG, BAO-YUN; ZHANG, XIAO-MEI; WANG, JING; CHEN, CAO; CHEN, LI-NA; LV, YAN; SHI, QI; DONG, XIAO-PING

    2016-01-01

    It is well known that the SMB-S15 cell line was originally established by cultures from the brains of mice affected by the Chandler scrapie strain, and this cell line may express PrPSc permanently. However, the infectivity of the S15-derived prions on experimental animals has not yet been well documented. In the present study, the cell lysates of SMB-S15 were intracerebrally inoculated into three different strains of mice, namely C57BL/6, Balb/c and CD1. Prion protein (PRNP) gene sequencing revealed the same encoded PrP proteins in the sequences of amino acids in the three strains of mice, in addition to a synonymous single nucleotide polymorphism (SNP) in CD1 mice. All infected mice developed typical experimental transmissible spongiform encephalopathies (TSEs) approximately six months post-infection. The clinical features of three infected mice were comparable. The pathogenic characteristics, such as the electrophoretic and glycosylation profiles and proteinase K (PK) resistance of PrPSc molecules, as well as the neuropathological characteristics, such as spongiform vacuolation, PrPSc deposits in cortex regions, astrogliosis and activated microglia, were also similar in all three strains of infected mice. However, PrPSc deposits in the cerebellums of CD1 mice were significantly fewer, which was linked with the observation that lower numbers of CD1 mice presented cerebellum-associated symptoms. Successive inoculation of the individual strains of mice with brain homogenates from the infected mice also induced typical experimental scrapie. The data in the present study thus confirm that the prion agent in SMB-S15 cells causes stable infectivity in different types of mice with distinct phenotypes after long-term propagation in vitro. The present study also provides further scrapie rodent models, which may be used in further studies. PMID:26820255

  3. Re-infection of the prion from the scrapie‑infected cell line SMB-S15 in three strains of mice, CD1, C57BL/6 and Balb/c.

    PubMed

    Xiao, Kang; Zhang, Bao-Yun; Zhang, Xiao-Mei; Wang, Jing; Chen, Cao; Chen, Li-Na; Lv, Yan; Shi, Qi; Dong, Xiao-Ping

    2016-03-01

    It is well known that the SMB-S15 cell line was originally established by cultures from the brains of mice affected by the Chandler scrapie strain, and this cell line may express PrPSc permanently. However, the infectivity of the S15-derived prions on experimental animals has not yet been well documented. In the present study, the cell lysates of SMB-S15 were intracerebrally inoculated into three different strains of mice, namely C57BL/6, Balb/c and CD1. Prion protein (PRNP) gene sequencing revealed the same encoded PrP proteins in the sequences of amino acids in the three strains of mice, in addition to a synonymous single nucleotide polymorphism (SNP) in CD1 mice. All infected mice developed typical experimental transmissible spongiform encephalopathies (TSEs) approximately six months post-infection. The clinical features of three infected mice were comparable. The pathogenic characteristics, such as the electrophoretic and glycosylation profiles and proteinase K (PK) resistance of PrPSc molecules, as well as the neuropathological characteristics, such as spongiform vacuolation, PrPSc deposits in cortex regions, astrogliosis and activated microglia, were also similar in all three strains of infected mice. However, PrPSc deposits in the cerebellums of CD1 mice were significantly fewer, which was linked with the observation that lower numbers of CD1 mice presented cerebellum-associated symptoms. Successive inoculation of the individual strains of mice with brain homogenates from the infected mice also induced typical experimental scrapie. The data in the present study thus confirm that the prion agent in SMB-S15 cells causes stable infectivity in different types of mice with distinct phenotypes after long-term propagation in vitro. The present study also provides further scrapie rodent models, which may be used in further studies. PMID:26820255

  4. Identification and detection of genetically modified papaya resistant to papaya ringspot virus strains in Thailand.

    PubMed

    Nakamura, Kosuke; Kondo, Kazunari; Kobayashi, Tomoko; Noguchi, Akio; Ohmori, Kiyomi; Takabatake, Reona; Kitta, Kazumi; Akiyama, Hiroshi; Teshima, Reiko; Nishimaki-Mogami, Tomoko

    2014-01-01

    Many lines of genetically modified (GM) papaya (Carica papaya Linnaeus) have been developed worldwide to resist infection from various strains of papaya ringspot virus (PRSV). We found an unidentified and unauthorized GM papaya in imported processed papaya food. Transgenic vector construct that provides resistance to the PRSV strains isolated in Thailand was detected. An original and specific real-time polymerase chain reaction method was generated to qualitatively detect the PRSV-Thailand-resistant GM papaya. PMID:24172062

  5. Physiological resistance of grasshopper mice (Onychomys spp.) to Arizona bark scorpion (Centruroides exilicauda) venom.

    PubMed

    Rowe, Ashlee H; Rowe, Matthew P

    2008-10-01

    Predators feeding on toxic prey may evolve physiological resistance to the preys' toxins. Grasshopper mice (Onychomys spp.) are voracious predators of scorpions in North American deserts. Two species of grasshopper mice (Onychomys torridus and Onychomys arenicola) are broadly sympatric with two species of potentially lethal bark scorpion (Centruroides exilicauda and Centruroides vittatus) in the Sonoran and Chihuahuan deserts, respectively. Bark scorpions produce toxins that selectively bind sodium (Na(+)) and potassium (K(+)) ion channels in vertebrate nerve and muscle tissue. We previously reported that grasshopper mice showed no effects of bark scorpion envenomation following natural stings. Here we conducted a series of toxicity tests to determine whether grasshopper mice have evolved resistance to bark scorpion neurotoxins. Five populations of grasshopper mice, either sympatric with or allopatric to bark scorpions, were injected with bark scorpion venom; LD50s were estimated for each population. All five populations of grasshopper mice demonstrated levels of venom resistance greater than that reported for non-resistant Mus musculus. Moreover, venom resistance in the mice showed intra- and interspecific variability that covaried with bark scorpion sympatry and allopatry, patterns consistent with the hypothesis that venom resistance in grasshopper mice is an adaptive response to feeding on their neurotoxic prey. PMID:18687353

  6. Effect of Lactobacillus plantarum Strain K21 on High-Fat Diet-Fed Obese Mice

    PubMed Central

    Wu, Chien-Chen; Weng, Wei-Lien; Lai, Wen-Lin; Tsai, Hui-Ping; Liu, Wei-Hsien; Lee, Meng-Hwan; Tsai, Ying-Chieh

    2015-01-01

    Recent studies have demonstrated beneficial effects of specific probiotics on alleviating obesity-related disorders. Here we aimed to identify probiotics with potential antiobesity activity among 88 lactic acid bacterial strains via in vitro screening assays, and a Lactobacillus plantarum strain K21 was found to harbor abilities required for hydrolyzing bile salt, reducing cholesterol, and inhibiting the accumulation of lipid in 3T3-L1 preadipocytes. Furthermore, effects of K21 on diet-induced obese (DIO) mice were examined. Male C57Bl/6J mice received a normal diet, high-fat diet (HFD), or HFD with K21 administration (109 CFU in 0.2 mL PBS/day) for eight weeks. Supplementation of K21, but not placebo, appeared to alleviate body weight gain and epididymal fat mass accumulation, reduce plasma leptin levels, decrease cholesterol and triglyceride levels, and mitigate liver damage in DIO mice. Moreover, the hepatic expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) related to adipogenesis was significantly downregulated in DIO mice by K21 intervention. We also found that K21 supplementation strengthens intestinal permeability and modulates the amount of Lactobacillus spp., Bifidobacterium spp., and Clostridium perfringens in the cecal contents of DIO mice. In conclusion, our results suggest that dietary intake of K21 protects against the onset of HFD-induced obesity through multiple mechanisms of action. PMID:25802537

  7. Macrophage production during murine listeriosis: colony-stimulating factor 1 (CSF-1) and CSF-1-binding cells in genetically resistant and susceptible mice.

    PubMed Central

    Cheers, C; Stanley, E R

    1988-01-01

    The concentration of the macrophage-specific colony-stimulating factor (CSF-1) and the numbers of bone marrow and spleen cells with specific receptors for that factor have been investigated in a number of mouse strains under normal conditions and after infection with the facultative intracellular bacterium Listeria monocytogenes. The CSF-1 concentration in serum and tissue was markedly elevated in infected mice, the degree of stimulation reflecting the dose of L. monocytogenes. The CSF-1 titer did not correlate with genetic resistance or susceptibility of the mice to L. monocytogenes. In contrast to the effect of lipopolysaccharide, Listeria infection was able to increase the level of CSF-1 in the lipopolysaccharide nonresponder strain C3H/HeJ. In line with earlier findings on colony-forming cells, cells bearing receptors for CSF-1 in uninfected susceptible BALB/cJ mice were only half those in resistant C57BL/6J mice. After infection the majority of these cells disappeared from the bone marrow and spleen cells of both resistant and susceptible mice. The number of CSF-1 receptor-bearing cells in the normal bone marrow may determine the degree of resistance to L. monocytogenes. PMID:3262588

  8. Altered accumulation and subcellular disposition of testicular cadmium in inbred mice resistant to cadmium-induced testicular necrosis

    SciTech Connect

    Chellman, G.J.

    1985-01-01

    Rodent testis is one of the most sensitive mammalian tissues to the toxic effects of acutely administered Cd. However, numerous inbred mouse strains are resistant to Cd-induced testicular damage, even at lethal Cd doses; the mechanism of this resistance has not been determined. Therefore, testes of mice susceptible (129/J) or resistant (A/J) to Cd-induced damage were examined for possible differences in the accumulation and subcellular disposition of Cd. Twenty-four hours after subcutaneous injection of mice with 30 ..mu..moles CdCl/sub 2//kg, 129/J testes showed extensive interstitial hemorrhage and seminiferous tubule necrosis, while A/J testes appeared histologically normal. Testicular Cd accumulation was 5-6 times less in A/J mice than in 129/J mice at all time points examined. Chromatography of testicular cytosol on Sephadex G-75 Superfine revealed four Cd-binding peaks. Both 15 min and 6 hr after dosing, A/J testes had 14% more of the total tissue Cd bound to the 14,500 MW protein (Cd-BP III), compared to 129/J testes, Cd-BP III behaved like metallothionein during gel filtration and ion exchange chromatography. Additional mice were injected i.v. with 10 (129/J) or 45 (A/J) ..mu..moles CdCl/sub 2//kg to achieve equal testicular Cd concentrations (approx. 4 nmoles Cd/g testis). Twenty-four hours later, 129/J testes were necrotic while A/J testes showed no microscopic evidence of damage. Therefore, resistance of A/J testes to Cd is not determined solely by decreased Cd accumulation, but is associated with increased binding of testicular Cd to Cd-BP III.

  9. Absence of strong strain effects in behavioral analyses of Shank3-deficient mice

    PubMed Central

    Drapeau, Elodie; Dorr, Nate P.; Elder, Gregory A.; Buxbaum, Joseph D.

    2014-01-01

    Haploinsufficiency of SHANK3, caused by chromosomal abnormalities or mutations that disrupt one copy of the gene, leads to a neurodevelopmental syndrome called Phelan-McDermid syndrome, symptoms of which can include absent or delayed speech, intellectual disability, neurological changes and autism spectrum disorders. The SHANK3 protein forms a key structural part of the post-synaptic density. We previously generated and characterized mice with a targeted disruption of Shank3 in which exons coding for the ankyrin-repeat domain were deleted and expression of full-length Shank3 was disrupted. We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions, in Shank3 heterozygous mice. Changes in phenotype owing to a mutation at a single locus are quite frequently modulated by other loci, most dramatically when the entire genetic background is changed. In mice, each strain of laboratory mouse represents a distinct genetic background and alterations in phenotype owing to gene knockout or transgenesis are frequently different across strains, which can lead to the identification of important modifier loci. We have investigated the effect of genetic background on phenotypes of Shank3 heterozygous, knockout and wild-type mice, using C57BL/6, 129SVE and FVB/Ntac strain backgrounds. We focused on observable behaviors with the goal of carrying out subsequent analyses to identify modifier loci. Surprisingly, there were very modest strain effects over a large battery of analyses. These results indicate that behavioral phenotypes associated with Shank3 haploinsufficiency are largely strain-independent. PMID:24652766

  10. Complete Genome Sequence of Staphylococcus aureus FCFHV36, a Methicillin-Resistant Strain Heterogeneously Resistant to Vancomycin

    PubMed Central

    Silveira, Alessandro Conrado de Oliveira; Lima Moraes, Aline da Costa; Pérez-Chaparro, Paula Juliana; Ferreira Silva, Manoella; Almeida, Lara Mendes; d’Azevedo, Pedro Alves; Mamizuka, Elsa Masae

    2015-01-01

    We report here the sequence of the entire chromosome of Staphylococcus aureus strain FCFHV36, a methicillin-resistant strain heterogeneously intermediate to vancomycin, bearing a type II staphylococcal chromosome cassette mec element (SCCmec), belonging to multilocus sequence type (MLST) 105, and isolated from a vertebra of a patient with osteomyelitis. PMID:26272570

  11. Severity of Group B Streptococcal Arthritis in Selected Strains of Laboratory Mice

    PubMed Central

    Puliti, Manuela; Bistoni, Francesco; von Hunolstein, Christina; Orefici, Graziella; Tissi, Luciana

    2001-01-01

    The susceptibilities of C3H/HeN, BALB/c, and C57BL/6N mouse strains to group B streptococci (GBS) infection were evaluated. C3H/HeN mice developed severe polyarthitis; mild lesions and no lesions were observed in BALB/c and C57BL/6N mice, respectively. A correlation between the severity of arthritis, the number of GBS in the joints, and local interleukin-6 and interleukin-1β production was evident. PMID:11119551

  12. Reliability of transcutaneous measurement of renal function in various strains of conscious mice.

    PubMed

    Schock-Kusch, Daniel; Geraci, Stefania; Ermeling, Esther; Shulhevich, Yury; Sticht, Carsten; Hesser, Juergen; Stsepankou, Dzmitry; Neudecker, Sabine; Pill, Johannes; Schmitt, Roland; Melk, Anette

    2013-01-01

    Measuring renal function in laboratory animals using blood and/or urine sampling is not only labor-intensive but puts also a strain on the animal. Several approaches for fluorescence based transcutaneous measurement of the glomerular filtration rate (GFR) in laboratory animals have been developed. They allow the measurement of GFR based on the elimination kinetics of fluorescent exogenous markers. None of the studies dealt with the reproducibility of the measurements in the same animals. Therefore, the reproducibility of a transcutaneous GFR assessment method was investigated using the fluorescent renal marker FITC-Sinistrin in conscious mice in the present study. We performed two transcutaneous GFR measurements within three days in five groups of mice (Balb/c, C57BL/6, SV129, NMRI at 3-4 months of age, and a group of 24 months old C57BL/6). Data were evaluated regarding day-to-day reproducibility as well as intra- and inter-strain variability of GFR and the impact of age on these parameters. No significant differences between the two subsequent GFR measurements were detected. Fastest elimination for FITC-Sinistrin was detected in Balb/c with significant differences to C57BL/6 and SV129 mice. GFR decreased significantly with age in C57BL/6 mice. Evaluation of GFR in cohorts of young and old C57BL/6 mice from the same supplier showed high consistency of GFR values between groups. Our study shows that the investigated technique is a highly reproducible and reliable method for repeated GFR measurements in conscious mice. This gentle method is easily used even in old mice and can be used to monitor the age-related decline in GFR. PMID:23977062

  13. Comparative sensitivity and resistance of some strains of Pseudomonas aeruginosa and Pseudomonas stutzeri to antibacterial agents

    PubMed Central

    Russell, A. D.; Mills, A. P.

    1974-01-01

    A comparison has been made of the sensitivities to various antibiotic and non-antibiotic substances of some strains of Pseudomonas aeruginosa and P. stutzeri, the latter including strains isolated from eye and other cosmetic products and from other sources. Whereas P. aeruginosa strains showed a high resistance to cetrimide and to benzalkonium chloride, the P. stutzeri strains were generally more sensitive to these and to chlorhexidine. The P. stutzeri strains were also more sensitive to the various antibiotics tested. The loss of the ability to transfer an R factor by two strains of P. aeruginosa caused no significant change in their drug sensitivity pattern. PMID:4369876

  14. Neurotoxicity of two Cylindrospermopsis raciborskii (cyanobacteria) strains to mice, Daphnia, and fish.

    PubMed

    Zagatto, Pedro A; Buratini, Sandra V; Aragão, Márcia A; Ferrão-Filho, Aloysio S

    2012-04-01

    In recent decades, toxic cyanobacterial blooms have become frequent in the drinking water supply and have caused serious deleterious effects to domestic and wild animals, as well as to humans. Two strains of the cyanobacterium species Cylindrospermopsis raciborskii (T2 and T3) were isolated from the Billings Reservoir (São Paulo, Brazil) and cultured in the laboratory for use in acute toxicity tests with mice, micro crustaceans, and fish. The results showed high toxicity of both strains in mouse bioassays (median lethal dose [LD50]; 24 h = 9.6 and 27 mg/kg; intraperitoneal injections). The symptomatology presented by mice was typical of neurotoxicosis, such as trembling, ataxia, convulsions and death by respiratory arrest. Acute and chronic effects were observed in Daphnia similis and Ceriodaphnia dubia, such as immobilization and reduced fitness, respectively. Although acute effects were not detected on the adult fish Danio rerio, chronic toxicity was observed for its larval stage. Although both strains showed high toxicity to all organisms, no consistent pattern was seen between the different bioassays and strains. The results also showed that C. raciborskii toxins are stable to heat and to extreme pH variations. Because of high toxicity of these strains and the potential risk to human health, the authors propose a revision of the legislation regarding safety factors for drinking water supply. PMID:22278803

  15. PCR-based identification of methicillin-resistant Staphylococcus aureus strains and their antibiotic resistance profiles

    PubMed Central

    Pournajaf, Abazar; Ardebili, Abdollah; Goudarzi, Leyla; Khodabandeh, Mahmoud; Narimani, Tahmineh; Abbaszadeh, Hassan

    2014-01-01

    Objective To evaluated the PCR for mecA gene compared with the conventional oxacillin disk diffusion method for methicillin-resistant Staphylococcus aureus (S. aureus) identification. Methods A total of 292 S. aureus strains were isolated from various clinical specimens obtained from hospitalized patients. Susceptibility test to several antimicrobial agents was performed by disk diffusion agar according to Clinical and Laboratory Standards Institute guidelines. The PCR amplification of the mecA gene was carried out in all the clinical isolates. Results Among antibiotics used in our study, penicillin showed the least anti-staphylococcal activity and vancomycin was the most effective. The rate of methicillin-resistant S. aureus prevalence determined by oxacillin disk diffusion method was 47.6%; whereas, 45.1% of S. aureus isolates were mecA- positive in the PCR assay. Conclusions This study is suggestive that the PCR for detection of mecA gene is a fast, accurate and valuable diagnostic tool, particularly in hospitals in areas where methicillin-resistant S. aureus is endemic. PMID:25183100

  16. Differences in Antibiotic Resistance Patterns of Enterococcus faecalis and Enterococcus faecium Strains Isolated from Farm and Pet Animals

    PubMed Central

    Butaye, Patrick; Devriese, Luc A.; Haesebrouck, Freddy

    2001-01-01

    The prevalence of acquired resistance in 146 Enterococcus faecium and 166 Enterococcus faecalis strains from farm and pet animals, isolated in 1998 and 1999 in Belgium, against antibiotics used for growth promotion and for therapy was determined. Acquired resistance against flavomycin and monensin, two antibiotics used solely for growth promotion, was not detected. Avoparcin (glycopeptide) resistance was found sporadically in E. faecium only. Avilamycin resistance was almost exclusively seen in strains from farm animals. Resistance rates were higher in E. faecium strains from broiler chickens than in strains from other animal groups with tylosin and virginiamycin and in E. faecalis as well as in E. faecium strains with narasin and bacitracin. Resistance against ampicillin was mainly found among E. faecium strains from pets and was absent in E. faecalis. Tetracycline resistance occurred most often in strains from farm animals, while enrofloxacin resistance, only found in E. faecalis, occurred equally among strains from all origins. Resistance against gentamicin was very rare in broiler strains, whereas resistance rates were high in strains from other origins. It can be concluded that resistance against antibiotics used solely for growth promotion was more prevalent in E. faecium strains than in E. faecalis strains. With few exceptions, resistance against the different categories of antibiotics was more prevalent in strains from farm animals than in those from pets. PMID:11302798

  17. Differences in antibiotic resistance patterns of Enterococcus faecalis and Enterococcus faecium strains isolated from farm and pet animals.

    PubMed

    Butaye, P; Devriese, L A; Haesebrouck, F

    2001-05-01

    The prevalence of acquired resistance in 146 Enterococcus faecium and 166 Enterococcus faecalis strains from farm and pet animals, isolated in 1998 and 1999 in Belgium, against antibiotics used for growth promotion and for therapy was determined. Acquired resistance against flavomycin and monensin, two antibiotics used solely for growth promotion, was not detected. Avoparcin (glycopeptide) resistance was found sporadically in E. faecium only. Avilamycin resistance was almost exclusively seen in strains from farm animals. Resistance rates were higher in E. faecium strains from broiler chickens than in strains from other animal groups with tylosin and virginiamycin and in E. faecalis as well as in E. faecium strains with narasin and bacitracin. Resistance against ampicillin was mainly found among E. faecium strains from pets and was absent in E. faecalis. Tetracycline resistance occurred most often in strains from farm animals, while enrofloxacin resistance, only found in E. faecalis, occurred equally among strains from all origins. Resistance against gentamicin was very rare in broiler strains, whereas resistance rates were high in strains from other origins. It can be concluded that resistance against antibiotics used solely for growth promotion was more prevalent in E. faecium strains than in E. faecalis strains. With few exceptions, resistance against the different categories of antibiotics was more prevalent in strains from farm animals than in those from pets. PMID:11302798

  18. Identification and characterization of a serious multidrug resistant Stenotrophomonas maltophilia strain in China.

    PubMed

    Zhao, Yan; Niu, Wenkai; Sun, Yanxia; Hao, Huaijie; Yu, Dong; Xu, Guangyang; Shang, Xueyi; Tang, Xueping; Lu, Sijing; Yue, Junjie; Li, Yan

    2015-01-01

    An S. maltophilia strain named WJ66 was isolated from a patient; WJ66 showed resistance to more antibiotics than the other S. maltophilia strains. This bacteraemia is resistant to sulphonamides, or fluoroquinolones, while the representative strain of S. maltophilia, K279a, is sensitive to both. To explore drug resistance determinants of this strain, the draft genome sequence of WJ66 was determined and compared to other S. maltophilia sequences. Genome sequencing and genome-wide evolutionary analysis revealed that WJ66 was highly homologous with the strain K279a, but strain WJ66 contained additional antibiotic resistance genes. Further analysis confirmed that strain WJ66 contained an amino acid substitution (Q83L) in fluoroquinolone target GyrA and carried a class 1 integron, with an aadA2 gene in the resistance gene cassette. Homology analysis from the pathogen-host interaction database showed that strain WJ66 lacks raxST and raxA, which is consistent with K279a. Comparative genomic analyses revealed that subtle nucleotide differences contribute to various significant phenotypes in close genetic relationship strains. PMID:25654114

  19. Development and Characterization of Rifampicin Resistant Flavobacterium Psychrophilum Strains and Their Potential as Live Attenuated Vaccine Candidates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have demonstrated that passage of pathogenic bacteria on increasing concentrations of the antibiotic rifampicin leads to the attenuation of virulence and these resistant strains may serve as live attenuated vaccines. Two rifampicin resistant strains of Flavobacterium psychrophilum,...

  20. Performance of rhizomania resistant sugarbeet under normal and resistance-breaking strains of Beet necrotic yellow vein virus.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rhizomania in sugarbeet (Beta vulgaris) is caused by Beet necrotic yellow vein virus (BNYVV). In current commercial cultivars, resistance to BNYVV is conditioned primarily by the allele Rz1. Since 2003, observations indicate that Rz1 has been compromised by resistance-breaking strains of BNYVV (RB-B...

  1. Surface changes and polymyxin interactions with a resistant strain of Klebsiella pneumoniae

    PubMed Central

    Velkov, Tony; Deris, Zakuan Z; Huang, Johnny X; Azad, Mohammad AK; Butler, Mark; Sivanesan, Sivashangarie; Kaminskas, Lisa M; Dong, Yao-Da; Boyd, Ben; Baker, Mark A; Cooper, Matthew A; Nation, Roger L; Li, Jian

    2014-01-01

    This study examines the interaction of polymyxin B and colistin with the surface and outer membrane components of a susceptible and resistant strain of Klebsiella pneumoniae. The interaction between polymyxins and bacterial membrane and isolated LPS from paired wild type and polymyxin-resistant strains of K. pneumoniae were examined with N-phenyl-1-naphthylamine (NPN) uptake, fluorometric binding and thermal shift assays, lysozyme and deoxycholate sensitivity assays, and by 1H NMR. LPS from the polymyxin-resistant strain displayed a reduced binding affinity for polymyxins B and colistin in comparison with the wild type LPS. The outer membrane NPN permeability of the resistant strain was greater compared with the susceptible strain. Polymyxin exposure enhanced the permeability of the outer membrane of the wild type strain to lysozyme and deoxycholate, whereas polymyxin concentrations up to 32 mg/ml failed to permeabilize the outer membrane of the resistant strain. Zeta potential measurements revealed that mid-logarithmic phase wild type cells exhibited a greater negative charge than the mid-logarithmic phase-resistant cells. Taken together, our findings suggest that the resistant derivative of K. pneumoniae can block the electrostatically driven first stage of polymyxin action, which thereby renders the hydrophobically driven second tier of polymyxin action on the outer membrane inconsequential. PMID:23887184

  2. Abnormalities in the WFU strain of Taenia crassiceps (Cyclophyllidea: Taeniidae) following years of propagation in mice.

    PubMed

    Aguilar-Vega, L; García-Prieto, L; Zurabian, R

    2016-09-01

    Asexually proliferating Taenia crassiceps (Zeder, 1800) metacestodes isolated within past decades have been successfully sub-cultured under experimental conditions using Mus musculus Linnaeus, 1758 mice. However, during their development, morphological irregularities of scolex structures have been reported in two of the three strains of this cestode species maintained in mice - ORF and KBS. The main goal of this work is to describe the abnormalities observed in a sample of 118 cysticerci of the third T. crassiceps strain used at present - WFU. Morphological abnormalities were detected in 39.8% of the evaginated scoleces; they consisted of supernumerary suckers (n= 2), duplicated (n= 2) or absent rostellum (n= 1), as well as absent or aberrant (n= 29) hooks, which were significantly shorter when compared to the large and short hook lengths referred to in the literature. PMID:26264231

  3. Comparative Genomics of Environmental and Clinical Stenotrophomonas maltophilia Strains with Different Antibiotic Resistance Profiles

    PubMed Central

    Youenou, Benjamin; Favre-Bonté, Sabine; Bodilis, Josselin; Brothier, Elisabeth; Dubost, Audrey; Muller, Daniel; Nazaret, Sylvie

    2015-01-01

    Stenotrophomonas maltophilia, a ubiquitous Gram-negative γ-proteobacterium, has emerged as an important opportunistic pathogen responsible for nosocomial infections. A major characteristic of clinical isolates is their high intrinsic or acquired antibiotic resistance level. The aim of this study was to decipher the genetic determinism of antibiotic resistance among strains from different origins (i.e., natural environment and clinical origin) showing various antibiotic resistance profiles. To this purpose, we selected three strains isolated from soil collected in France or Burkina Faso that showed contrasting antibiotic resistance profiles. After whole-genome sequencing, the phylogenetic relationships of these 3 strains and 11 strains with available genome sequences were determined. Results showed that a strain’s phylogeny did not match their origin or antibiotic resistance profiles. Numerous antibiotic resistance coding genes and efflux pump operons were revealed by the genome analysis, with 57% of the identified genes not previously described. No major variation in the antibiotic resistance gene content was observed between strains irrespective of their origin and antibiotic resistance profiles. Although environmental strains generally carry as many multidrug resistant (MDR) efflux pumps as clinical strains, the absence of resistance–nodulation–division (RND) pumps (i.e., SmeABC) previously described to be specific to S. maltophilia was revealed in two environmental strains (BurA1 and PierC1). Furthermore the genome analysis of the environmental MDR strain BurA1 showed the absence of SmeABC but the presence of another putative MDR RND efflux pump, named EbyCAB on a genomic island probably acquired through horizontal gene transfer. PMID:26276674

  4. Resistance fail strain gage technology as applied to composite materials

    NASA Technical Reports Server (NTRS)

    Tuttle, M. E.; Brinson, H. F.

    1985-01-01

    Existing strain gage technologies as applied to orthotropic composite materials are reviewed. The bonding procedures, transverse sensitivity effects, errors due to gage misalignment, and temperature compensation methods are addressed. Numerical examples are included where appropriate. It is shown that the orthotropic behavior of composites can result in experimental error which would not be expected based on practical experience with isotropic materials. In certain cases, the transverse sensitivity of strain gages and/or slight gage misalignment can result in strain measurement errors.

  5. Genetic Background and Antibiotic Resistance of Staphylococcus aureus Strains Isolated in the Republic of Georgia

    PubMed Central

    Revazishvili, Tamara; Bakanidze, Lela; Gomelauri, Tsaro; Zhgenti, Ekaterine; Chanturia, Gvantsa; Kekelidze, Merab; Rajanna, Chythanya; Kreger, Arnold; Sulakvelidze, Alexander

    2006-01-01

    The genetic composition and antibiotic sensitivities of 50 clinical isolates of Staphylococcus aureus obtained from various clinics in the Republic of Georgia were characterized. S. aureus strains ATCC 700699 and ATCC 29737 were included as reference standards in all analyses. All 52 strains had identical 16S rRNA profiles. In contrast, pulsed-field gel electrophoresis (PFGE) identified 20 distinct PFGE types among the 52 strains examined, which indicates that PFGE is more discriminating than is 16S rRNA sequence analysis for differentiating S. aureus strains. The results of our PFGE typing also suggest that multiple genetic subpopulations (related at the ca. 85% similarity level, based on their SmaI PFGE patterns) exist among the Georgian S. aureus strains. Twenty-two of the 50 Georgian strains were methicillin resistant and PCR positive for mecA, and 5 strains were methicillin sensitive even though they possessed mecA. None of the strains were vancomycin resistant or contained vanA. The nucleotide sequences of mecA fragments obtained from all mecA-containing strains were identical. Our data indicate that the population of S. aureus strains in Georgia is fairly homogeneous and that the prevalence of methicillin-resistant, mecA-positive strains is relatively high in that country. PMID:17021070

  6. Molecular characterisation of quinolone-resistant Shigella strains isolated in Tehran, Iran.

    PubMed

    Ranjbar, Reza; Behnood, Vahid; Memariani, Hamed; Najafi, Ali; Moghbeli, Majid; Mammina, Caterina

    2016-06-01

    Over the past few years, the number of Shigella strains resistant to nalidixic acid has increased and has made the selection of effective antimicrobial therapy more difficult. The purpose of this study was to investigate the molecular mechanism of quinolone resistance in Shigella strains. Shigella strains isolated from 1100 diarrhoeal patients in Tehran, Iran, were assessed for their susceptibility to nalidixic acid prior to PCR-RFLP and sequence analysis of their quinolone resistance genes. Among 73 Shigella strains isolated, 23 (31.5%) were resistant to nalidixic acid. The most common Shigella spp. was Shigella sonnei (54; 74.0%). Of the 23 quinolone-resistant isolates, 4 (17.4%) (including 2 Shigella flexneri, 1 S. sonnei and 1 Shigella boydii) contained the qnrS gene. However, none of the isolates harboured qnrA or qnrB genes. PCR-RFLP analysis of gyrA showed a mutation profile in two nalidixic acid-resistant strains, including one S. sonnei and one S. flexneri. Sequencing of mutant gyrA genes revealed a point mutation at position 83, resulting in the replacement of serine by leucine. In conclusion, molecular mechanisms of resistance to quinolones were identified in 6 of 23 Shigella isolates. Other possible mechanisms of resistance should also be investigated for better characterisation of quinolone-resistant Shigella isolates. PMID:27436462

  7. RNAi validation of resistance genes and their interactions in the highly DDT-resistant 91-R strain of Drosophila melanogaster.

    PubMed

    Gellatly, Kyle J; Yoon, Kyong Sup; Doherty, Jeffery J; Sun, Weilin; Pittendrigh, Barry R; Clark, J Marshall

    2015-06-01

    4,4'-dichlorodiphenyltrichloroethane (DDT) has been re-recommended by the World Health Organization for malaria mosquito control. Previous DDT use has resulted in resistance, and with continued use resistance will increase in terms of level and extent. Drosophila melanogaster is a model dipteran that has many available genetic tools, numerous studies done on insecticide resistance mechanisms, and is related to malaria mosquitoes allowing for extrapolation. The 91-R strain of D. melanogaster is highly resistant to DDT (>1500-fold), however, there is no mechanistic scheme that accounts for this level of resistance. Recently, reduced penetration, increased detoxification, and direct excretion have been identified as resistance mechanisms in the 91-R strain. Their interactions, however, remain unclear. Use of UAS-RNAi transgenic lines of D. melanogaster allowed for the targeted knockdown of genes putatively involved in DDT resistance and has validated the role of several cuticular proteins (Cyp4g1 and Lcp1), cytochrome P450 monooxygenases (Cyp6g1 and Cyp12d1), and ATP binding cassette transporters (Mdr50, Mdr65, and Mrp1) involved in DDT resistance. Further, increased sensitivity to DDT in the 91-R strain after intra-abdominal dsRNA injection for Mdr50, Mdr65, and Mrp1 was determined by a DDT contact bioassay, directly implicating these genes in DDT efflux and resistance. PMID:26047118

  8. Cadmium- and mercury-resistant Bacillus strains from a salt marsh and from Boston Harbor

    SciTech Connect

    Mahler, I.; Levinson, H.S.; Wang, Y.; Halvorson, H.O.

    1986-12-01

    Bacteria resistant to cadmium or mercury or both were isolated from the Great Sippewissett Marsh (Cape Cod, Mass.) and from Boston Harbor. Many of these metal-resistant isolates were gram-positive aerobic sporeformers, although not necessarily isolated as spores. Although several of the isolated strains bore plasmids, cadmium and mercury resistances appeared to be, for the most part, chromosomally encoded. DNA sequence homology of the gram-positive cadmium- and mercury-resistant isolates was not demonstrable with metal resistance genes from plasmids of either gram-positive (pI258) or gram-negative (pDB7) origin. Cadmium resistance of all the marsh isolates tested resulted from reduced Cd/sup 2 +/ transport. On the other hand, three cadmium-resistant harbor isolates displayed considerable influx but no efflux of Cd/sup 2 +/. Hg-resistant strains detoxified mercury by transforming Hg/sup 2 +/ to volatile Hg0 via mercuric reductase.

  9. Effects of environmental enrichment on males of a docile inbred strain of mice.

    PubMed

    Marashi, Vera; Barnekow, Angelika; Sachser, Norbert

    2004-10-15

    Environmental enrichment is intended to improve the welfare of laboratory animals. However, regarding male mice, numerous studies indicate an increase in aggressive behavior due to cage structuring. On the one hand, this might be a problem concerning animal welfare. On the other hand, enrichment is though to hamper environmental standardization and to increase variability of data. Furthermore, increasing fights, arousal, and/or injury in enriched housed animals might superimpose other (positive) environmental effects on behavior and physiology. Therefore, the present study investigated effects of environmental enrichment on behavioral, endocrinological, and immunological parameters in male mice of the docile inbred strain ABG. From weaning until day 77+/-3 of life, animals were kept in stable sibling groups of four under three different housing conditions: (A) nonstructured Makrolon type III laboratory cages ("standard housing"=S); (B) equivalent laboratory cages that were enriched with a box and scaffolding ("enriched housing"=E); and (C) spacious terrariums that were structured richly ("super-enriched housing"=SE). No differences in agonistic behavior, levels of plasma corticosterone (CORT), and activities of adrenal tyrosine hydroxylase (TH) existed among S-, E-, and SE-housed ABG males. Play behavior and general activity increased significantly with increasing enrichment. Concerning immunological parameters, males of both forms of enriched housing showed significantly lower percentages of CD4 and CD8 cells compared to S-housed mice. However, regarding the ratio of CD4/CD8 cells, IL-2, IL-4, IL-10, IFN-gamma, IgG1, and IgG2a, no significant housing-dependent differences were found. Enrichment did neither hamper standardization nor negatively influence the variability of physiological parameters. In summary, using a docile strain of mice revealed the positive effects of environmental enrichment also on male mice. The lack of adverse effects on behavior

  10. Effect of Regular Exercise on Inflammation Induced by Drug-resistant Staphylococcus aureus 3089 in ICR mice

    PubMed Central

    Lee, Jong-Kook; Luchian, Tudor; Park, Yoonkyung

    2015-01-01

    Obesity is often associated with irregular dietary habits and reduced physical activity. Regular exercise induces a metabolic response that includes increased expression of various cytokines, signaling proteins and hormones, and reduced adipocyte size. In this study, mice performed a swimming exercise for 10 min/day, 5 days/week for 3 weeks. We then investigated the effect of this exercise regimen on inflammation induced by infection with drug-resistant Staphylococcus aureus strain 3089 (DRSA). In humans, DRSA causes dermatitis and pneumonitis. Similarly, DRSA induced inflammatory pneumonitis in both no-exercise (No-EX) and swim-trained (SW-EX) ICR mice. Regular exercise increased levels of the pro-inflammatory cytokines TNF-α and IL-1β and nitric oxide in both serum and whole lung tissue in SW-EX, as compared to No-EX control mice. Moreover, levels of the antimicrobial peptide cathelicidin were significantly increased in visceral adipose tissue and whole lung tissue in the SW-EX group, and this was accompanied by a reduction in the size of visceral adipocytes. In addition, levels of the inflammation marker peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) were not increased in the lung tissue of SW-EX mice. These findings suggest that in these model mice, regular exercise strengthens immune system responses, potentially preventing or mitigating infectious disease. PMID:26542343

  11. SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus Strain N315.

    PubMed

    Liu, Xiaoyu; Zhang, Shijie; Sun, Baolin

    2016-06-01

    Increasing cases of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains in healthy individuals have raised concerns worldwide. MRSA strains are resistant to almost the entire family of β-lactam antibiotics due to the acquisition of an extra penicillin-binding protein, PBP2a. Studies have shown that spoVG is involved in oxacillin resistance, while the regulatory mechanism remains elusive. In this study, we have found that SpoVG plays a positive role in oxacillin resistance through promoting cell wall synthesis and inhibiting cell wall degradation in MRSA strain N315. Deletion of spoVG in strain N315 led to a significant decrease in oxacillin resistance and a dramatic increase in Triton X-100-induced autolytic activity simultaneously. Real-time quantitative reverse transcription-PCR revealed that the expression of 8 genes related to cell wall metabolism or oxacillin resistance was altered in the spoVG mutant. Electrophoretic mobility shift assay indicated that SpoVG can directly bind to the putative promoter regions of lytN (murein hydrolase), femA, and lytSR (the two-component system). These findings suggest a molecular mechanism in which SpoVG modulates oxacillin resistance by regulating cell wall metabolism in MRSA. PMID:27001809

  12. Identification and deconvolution of cross-resistance signals from antimalarial compounds using multidrug-resistant Plasmodium falciparum strains.

    PubMed

    Chugh, Monika; Scheurer, Christian; Sax, Sibylle; Bilsland, Elizabeth; van Schalkwyk, Donelly A; Wicht, Kathryn J; Hofmann, Natalie; Sharma, Anil; Bashyam, Sridevi; Singh, Shivendra; Oliver, Stephen G; Egan, Timothy J; Malhotra, Pawan; Sutherland, Colin J; Beck, Hans-Peter; Wittlin, Sergio; Spangenberg, Thomas; Ding, Xavier C

    2015-02-01

    Plasmodium falciparum, the most deadly agent of malaria, displays a wide variety of resistance mechanisms in the field. The ability of antimalarial compounds in development to overcome these must therefore be carefully evaluated to ensure uncompromised activity against real-life parasites. We report here on the selection and phenotypic as well as genotypic characterization of a panel of sensitive and multidrug-resistant P. falciparum strains that can be used to optimally identify and deconvolute the cross-resistance signals from an extended panel of investigational antimalarials. As a case study, the effectiveness of the selected panel of strains was demonstrated using the 1,2,4-oxadiazole series, a newly identified antimalarial series of compounds with in vitro activity against P. falciparum at nanomolar concentrations. This series of compounds was to be found inactive against several multidrug-resistant strains, and the deconvolution of this signal implicated pfcrt, the genetic determinant of chloroquine resistance. Targeted mode-of-action studies further suggested that this new chemical series might act as falcipain 2 inhibitors, substantiating the suggestion that these compounds have a site of action similar to that of chloroquine but a distinct mode of action. New antimalarials must overcome existing resistance and, ideally, prevent its de novo appearance. The panel of strains reported here, which includes recently collected as well as standard laboratory-adapted field isolates, is able to efficiently detect and precisely characterize cross-resistance and, as such, can contribute to the faster development of new, effective antimalarial drugs. PMID:25487796

  13. Identification and Deconvolution of Cross-Resistance Signals from Antimalarial Compounds Using Multidrug-Resistant Plasmodium falciparum Strains

    PubMed Central

    Chugh, Monika; Scheurer, Christian; Sax, Sibylle; Bilsland, Elizabeth; van Schalkwyk, Donelly A.; Wicht, Kathryn J.; Hofmann, Natalie; Sharma, Anil; Bashyam, Sridevi; Singh, Shivendra; Oliver, Stephen G.; Egan, Timothy J.; Malhotra, Pawan; Sutherland, Colin J.; Beck, Hans-Peter; Wittlin, Sergio; Spangenberg, Thomas

    2014-01-01

    Plasmodium falciparum, the most deadly agent of malaria, displays a wide variety of resistance mechanisms in the field. The ability of antimalarial compounds in development to overcome these must therefore be carefully evaluated to ensure uncompromised activity against real-life parasites. We report here on the selection and phenotypic as well as genotypic characterization of a panel of sensitive and multidrug-resistant P. falciparum strains that can be used to optimally identify and deconvolute the cross-resistance signals from an extended panel of investigational antimalarials. As a case study, the effectiveness of the selected panel of strains was demonstrated using the 1,2,4-oxadiazole series, a newly identified antimalarial series of compounds with in vitro activity against P. falciparum at nanomolar concentrations. This series of compounds was to be found inactive against several multidrug-resistant strains, and the deconvolution of this signal implicated pfcrt, the genetic determinant of chloroquine resistance. Targeted mode-of-action studies further suggested that this new chemical series might act as falcipain 2 inhibitors, substantiating the suggestion that these compounds have a site of action similar to that of chloroquine but a distinct mode of action. New antimalarials must overcome existing resistance and, ideally, prevent its de novo appearance. The panel of strains reported here, which includes recently collected as well as standard laboratory-adapted field isolates, is able to efficiently detect and precisely characterize cross-resistance and, as such, can contribute to the faster development of new, effective antimalarial drugs. PMID:25487796

  14. Macrolide Resistance in the Syphilis Spirochete, Treponema pallidum ssp. pallidum: Can We Also Expect Macrolide-Resistant Yaws Strains?

    PubMed

    Šmajs, David; Paštěková, Lenka; Grillová, Linda

    2015-10-01

    Treponema pallidum ssp. pallidum (TPA) causes over 10 million new cases of syphilis worldwide whereas T. pallidum ssp. pertenue (TPE), the causative agent of yaws, affects about 2.5 million people. Although penicillin remains the drug of choice in the treatment of syphilis, in penicillin-allergic patients, macrolides have been used in this indication since the 1950s. Failures of macrolides in syphilis treatment have been well documented in the literature and since 2000, there has been a dramatic increase in a number of clinical samples with macrolide-resistant TPA. Scarce data regarding the genetics of macrolide-resistant mutations in TPA suggest that although macrolide-resistance mutations have emerged independently several times, the increase in the proportion of TPA strains resistant to macrolides is mainly due to the spread of resistant strains, especially in developed countries. The emergence of macrolide resistance in TPA appears to require a two-step process including either A2058G or A2059G mutation in one copy of the 23S rRNA gene and a subsequent gene conversion unification of both rRNA genes. Given the enormous genetic similarity that was recently revealed between TPA and TPE strains, there is a low but reasonable risk of emergence and spread of macrolide-resistant yaws strains following azithromycin treatment. PMID:26217043

  15. Physiological implications of class IIa bacteriocin resistance in Listeria monocytogenes strains.

    PubMed

    Vadyvaloo, Viveka; Snoep, Jacky L; Hastings, John W; Rautenbach, Marina

    2004-02-01

    High-level resistance to class IIa bacteriocins has been directly associated with the absent EIIAB(Man) (MptA) subunit of the mannose-specific phosphoenolpyruvate-dependent phosphotransferase system (PTS) (EIIt(MAN)) in Listeria monocytogenes strains. Class IIa bacteriocin-resistant strains used in this study were a spontaneous resistant, L. monocytogenes B73-MR1, and a defined mutant, L. monocytogenes EGDe-mptA. Both strains were previously reported to have the EIIAB(Man) PTS component missing. This study shows that these class IIa bacteriocin-resistant strains have significantly decreased specific growth and glucose consumption rates, but they also have a significantly higher growth yield than their corresponding wild-type strains, L. monocytogenes B73 and L. monocytogenes EGDe, respectively. In the presence of glucose, the strains showed a shift from a predominantly lactic-acid to a mixed-acid fermentation. It is here proposed that elimination of the EIIAB(Man) in the resistant strains has caused a reduced glucose consumption rate and a reduced specific growth rate. The lower glucose consumption rate can be correlated to a shift in metabolism to a more efficient pathway with respect to ATP production per glucose, leading to a higher biomass yield. Thus, the cost involved in obtaining bacteriocin resistance, i.e. losing substrate transport capacity leading to a lower growth rate, is compensated for by a higher biomass yield. PMID:14766911

  16. Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection.

    PubMed

    Yang, Jiseon; Barrila, Jennifer; Roland, Kenneth L; Kilbourne, Jacquelyn; Ott, C Mark; Forsyth, Rebecca J; Nickerson, Cheryl A

    2015-06-01

    A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 10(5) CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580. PMID:26091096

  17. Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection

    PubMed Central

    Roland, Kenneth L.; Kilbourne, Jacquelyn; Ott, C. Mark; Forsyth, Rebecca J.; Nickerson, Cheryl A.

    2015-01-01

    A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 105 CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580. PMID:26091096

  18. Recall of acquired cellular resistance in mice by antigens from killed Brucella.

    PubMed

    Halliburton, B L; Hinsdill, R D

    1972-01-01

    Mice infected with Brucella abortus 19 were challenged intravenously with Listeria monocytogenes. Spleen assays to determine the number of viable Listeria cells present revealed that these mice were highly resistant to Listeria when challenged on day 17 of the Brucella infection. Resistance was absent in mice challenged on the 5th day and was declining in mice challenged on the 33rd day. Resistance could not be detected by day 49 of the Brucella infection but could be recalled by the injection of antigens from smooth B. abortus 2308. Thus, extracted antigens appeared to be as effective in recall as the live cells used in earlier studies. Similar injections of extracts from rough B. abortus 45/20, or from B. ovis REO 198, were also effective in recalling resistance; this suggests that the smooth surface agglutinogen may be relatively unimportant in recall. PMID:4632467

  19. Partial resistance to homologous challenge infections of the digenean Echinostoma caproni in ICR mice.

    PubMed

    Muñoz-Antoli, C; Cortés, A; Martín-Grau, C; Fried, B; Esteban, J G; Toledo, R

    2016-07-01

    In the present paper, we analyse the effect of a primary infection of ICR mice with Echinostoma caproni (Trematoda: Echinostomatidae) on the generation of resistance against homologous challenge infections. In ICR mice, E. caproni induces chronic infections concomitantly with strong responses characterized by the development of T-helper 1 (Th1)-type local immune responses with elevated levels of local interferon-gamma (IFN-γ) and inflammatory and antibody responses. Here, the effect of the response generated against a primary infection with E. caproni in the generation of resistance against subsequent homologous infections was analysed. For this purpose, ICR mice were challenged with metacercariae of E. caproni and the results obtained showed that primary infection induces partial resistance against subsequent homologous infections in ICR mice. This resistance was expressed as a reduced rate of infection, worm recovery and worm size, indicating that primary infection induces changes in the host, making a hostile environment for the development of the parasite. PMID:26202834

  20. Activities of Various 4-Aminoquinolines Against Infections with Chloroquine-Resistant Strains of Plasmodium falciparum1

    PubMed Central

    Schmidt, L. H.; Vaughan, Dennis; Mueller, Donna; Crosby, Ruth; Hamilton, Rebecca

    1977-01-01

    The studies reported here stemmed from a personal report by Geiman on the capacity of the 4-aminoquinoline amodiaquin to inhibit in vitro maturation of ring stages of the chloroquine-resistant Monterey strain of Plasmodium falciparum. This observation, confirmed in owl monkeys infected with this strain, led to a comparison of the activities of chloroquine, amodiaquin, amopyroquin, and dichlorquinazine (12,278 RP) against infections with various chloroquine-susceptible and chloroquine-resistant strains. The results showed that: (i) these 4-aminoquinolines were essentially equally active against infections with chloroquine-susceptible strains and (ii) the activities of amodiaquin, amopyroquin, and dichlorquinazine were reduced significantly in the face of chloroquine resistance, but (iii) well-tolerated doses of these compounds would cure infections with strains that fully resisted treatment with maximally tolerated doses of chloroquine. Two other 4-aminoquinolines, SN-8137 and SN-9584, which also exhibited activity against chloroquine-resistant parasites in vitro, displayed curative activity in monkeys infected with a chloroquine-resistant strain. These observations show that there is cross-resistance among the 4-aminoquinolines, confirming earlier findings, but indicate that the dimensions of this phenomenon are sufficiently limited so that some derivatives are therapeutically effective against infections refractory to maximally tolerated doses of chloroquine. PMID:406829

  1. Carbamate and pyrethroid resistance in the akron strain of Anopheles gambiae.

    PubMed

    Mutunga, James M; Anderson, Troy D; Craft, Derek T; Gross, Aaron D; Swale, Daniel R; Tong, Fan; Wong, Dawn M; Carlier, Paul R; Bloomquist, Jeffrey R

    2015-06-01

    Insecticide resistance in the malaria vector, Anopheles gambiae, is a serious problem, epitomized by the multi-resistant Akron strain, originally isolated in the country of Benin. Here we report resistance in this strain to pyrethroids and DDT (13-fold to 35-fold compared to the susceptible G3 strain), but surprisingly little resistance to etofenprox, a compound sometimes described as a "pseudo-pyrethroid." There was also strong resistance to topically-applied commercial carbamates (45-fold to 81-fold), except for the oximes aldicarb and methomyl. Biochemical assays showed enhanced cytochrome P450 monooxygenase and carboxylesterase activity, but not that of glutathione-S-transferase. A series of substituted α,α,α,-trifluoroacetophenone oxime methylcarbamates were evaluated for enzyme inhibition potency and toxicity against G3 and Akron mosquitoes. The compound bearing an unsubstituted phenyl ring showed the greatest toxicity to mosquitoes of both strains. Low cross resistance in Akron was retained by all analogs in the series. Kinetic analysis of acetylcholinesterase activity and its inhibition by insecticides in the G3 strain showed inactivation rate constants greater than that of propoxur, and against Akron enzyme inactivation rate constants similar to that of aldicarb. However, inactivation rate constants against recombinant human AChE were essentially identical to that of the G3 strain. Thus, the acetophenone oxime carbamates described here, though potent insecticides that control resistant Akron mosquitoes, require further structural modification to attain acceptable selectivity and human safety. PMID:26047119

  2. Carbamate and Pyrethroid Resistance in the Akron Strain of Anopheles gambiae

    PubMed Central

    Mutunga, James M.; Anderson, Troy D.; Craft, Derek T.; Gross, Aaron D.; Swale, Daniel R.; Tong, Fan; Wong, Dawn M.; Carlier, Paul R.; Bloomquist, Jeffrey R.

    2015-01-01

    Insecticide resistance in the malaria vector, Anopheles gambiae is a serious problem, epitomized by the multi-resistant Akron strain, originally isolated in the country of Benin. Here we report resistance in this strain to pyrethroids and DDT (13-fold to 35-fold compared to the susceptible G3 strain), but surprisingly little resistance to etofenprox, a compound sometimes described as a “pseudo-pyrethroid.” There was also strong resistance to topically-applied commercial carbamates (45-fold to 81-fold), except for the oximes aldicarb and methomyl. Biochemical assays showed enhanced cytochrome P450 monooxygenase and carboxylesterase activity, but not that of glutathione-S-transferase. A series of substituted α,α,α,-trifluoroacetophenone oxime methylcarbamates were evaluated for enzyme inhibition potency and toxicity against G3 and Akron mosquitoes. The compound bearing an unsubstituted phenyl ring showed the greatest toxicity to mosquitoes of both strains. Low cross resistance in Akron was retained by all analogs in the series. Kinetic analysis of acetylcholinesterase activity and its inhibition by insecticides in the G3 strain showed inactivation rate constants greater than that of propoxur, and against Akron enzyme inactivation rate constants similar to that of aldicarb. However, inactivation rate constants against recombinant human AChE were essentially identical to that of the G3 strain. Thus, the acetophenone oxime carbamates described here, though potent insecticides that control resistant Akron mosquitoes, require further structural modification to attain acceptable selectivity and human safety. PMID:26047119

  3. Sensitivity of antibiotic resistant and antibiotic susceptible Escherichia coli, Enterococcus and Staphylococcus strains against ozone.

    PubMed

    Heß, Stefanie; Gallert, Claudia

    2015-12-01

    Tolerance of antibiotic susceptible and antibiotic resistant Escherichia coli, Enterococcus and Staphylococcus strains from clinical and wastewater samples against ozone was tested to investigate if ozone, a strong oxidant applied for advanced wastewater treatment, will affect the release of antibiotic resistant bacteria into the aquatic environment. For this purpose, the resistance pattern against antibiotics of the mentioned isolates and their survival after exposure to 4 mg/L ozone was determined. Antibiotic resistance (AR) of the isolates was not correlating with higher tolerance against ozone. Except for ampicillin resistant E. coli strains, which showed a trend towards increased resistance, E. coli strains that were also resistant against cotrimoxazol, ciprofloxacin or a combination of the three antibiotics were similarly or less resistant against ozone than antibiotic sensitive strains. Pigment-producing Enterococcus casseliflavus and Staphylococcus aureus seemed to be more resistant against ozone than non-pigmented species of these genera. Furthermore, aggregation or biofilm formation apparently protected bacteria in subsurface layers from inactivation by ozone. The relatively large variance of tolerance against ozone may indicate that resistance to ozone inactivation most probably depends on several factors, where AR, if at all, does not play a major role. PMID:26608763

  4. Echinococcus granulosus pig strain (G7 genotype) protoscoleces did not develop secondary hydatid cysts in mice.

    PubMed

    Cucher, M; Mourglia-Ettlin, G; Prada, L; Costa, H; Kamenetzky, L; Poncini, C; Dematteis, S; Rosenzvit, M C

    2013-03-31

    Echinococcus granulosus, the aetiological agent of cystic hydatid disease, exists as a series of strains or genotypes which differ in biological features. Pig strain (G7 genotype) has been shown to differ from sheep strain (G1 genotype) in phenotypical characters such as intermediate host range, geographical distribution and rate of development of the adult worm. Since in vivo studies of different parasite genotypes can provide insights into host-parasite relationship we analysed for the first time the behaviour of E. granulosus G7 genotype protoscoleces in the murine experimental model. Our results show that G7 protoscoleces were unable to establish a regular infection in mice in contrast to G1 protoscoleces which developed intraperitoneal hydatid cysts. This inability was observed in co-infection experiments, i.e. even in the presence of a controlled immune response that allows G1 genotype protoscoleces establishment. In addition, the implantation of in vitro obtained E. granulosus G7 genotype microcysts resulted in a low percentage of hydatid cysts establishment. These results show a difference in the biological ability of both E. granulosus strains to develop secondary hydatid cysts in mice. We suggest that the comparison of infective and non infective genotypes of E. granulosus in the experimental host can be regarded as a new model to study the mechanisms of infection of Echinococcus spp. This knowledge could provide helpful information for the development of therapies, drugs and/or vaccines against cystic hydatid disease. PMID:23265812

  5. Loss of resistance to murine hepatitis virus strain 3 infection after treatment with corticosteroids is associated with induction of macrophage procoagulant activity.

    PubMed Central

    Fingerote, R J; Abecassis, M; Phillips, M J; Rao, Y S; Cole, E H; Leibowitz, J; Levy, G A

    1996-01-01

    Activation of the immune coagulation system has been implicated in the pathogenesis of liver injury following infection of inbred mice with murine hepatitis virus strain 3 (MHV-3). Following MHV-3 infection, macrophages isolated from MHV-3-susceptible and -semisusceptible inbred strains of mice express increased procoagulant activity (PCA), whereas macrophages from resistant strains express no increase in PCA over basal levels. The PCA induced by MHV-3 is a prothrombinase, encoded by the gene Fgl-2, which encodes a fibrinogen-like protein (musfiblp). In this study, MHV-3-resistant A/J mice treated with methylprednisolone prior to infection with MHV-3 developed elevated levels of alanine aminotransferase in serum and died within 10 days of infection, with histological findings of fulminant hepatitis. In vitro, macrophages isolated from A/J mice and pretreated with methylprednisolone produced a marked increase in functional PCA following infection with MHV-3. The PCA was shown to be a prothrombinase by its ability to cleave 125I-prothrombin. Northern blot analysis of RNA transcripts from these macrophages demonstrated increased transcription of the Fgl-2 gene relative to that in macrophages which had not been pretreated with methylprednisolone prior to MHV-3 infection. Methylprednisolone pretreatment of MHV-3-infected macrophages stabilized the Fgl-2 mRNA. Thus, loss of resistance to MHV-3 secondary to methylprednisolone therapy is associated with increased transcription and stability of Fgl-2 mRNA resulting in expression of the Fgl-2 gene product, musfiblp. These results provide further insight into mechanisms of PCA regulation in response to MHV-3 infection in inbred strains of mice. PMID:8676449

  6. Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.

    PubMed

    Zhang, Lu; Ru, Huan-wei; Chen, Fu-zeng; Jin, Chun-yan; Sun, Rui-feng; Fan, Xiao-yong; Guo, Ming; Mai, Jun-tao; Xu, Wen-xi; Lin, Qing-xia; Liu, Jun

    2016-02-01

    Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development. PMID:26643797

  7. Differential Immune Responses and Protective Effects in Avirulent Mycobacterial Strains Vaccinated BALB/c Mice.

    PubMed

    Liu, Laicheng; Fu, Ruiling; Yuan, Xuefeng; Shi, Chunwei; Wang, Shuling; Lu, Xianyu; Ma, Zhao; Zhang, Xiaoming; Qin, Weiyan; Fan, Xionglin

    2015-07-01

    Screening live mycobacterial vaccine candidates is the important strategy to develop new vaccines against adult tuberculosis (TB). In this study, the immunogenicity and protective efficacy of several avirulent mycobacterial strains including Mycobacterium smegmatis, M. vaccae, M. terrae, M. phlei, M. trivial, and M. tuberculosis H37Ra were compared with M. bovis BCG in BALB/c mice. Our results demonstrated that differential immune responses were induced in different mycobacterial species vaccinated mice. As BCG-vaccinated mice did, M. terrae immunization resulted in Th1-type responses in the lung, as well as splenocytes secreting IFN-γ against a highly conserved mycobacterial antigen Ag85A. M. smegmatis also induced the same splenocytes secreting IFN-γ as BCG and M. terrae did. In addition, M. terrae and M. smegmatis-immunized mice predominantly increased expression of IL-10 and TGF-β in the lung. Most importantly, mice vaccinated with H37Ra and M. vaccae could provide the same protection in the lung against virulent M. tuberculosis challenge as BCG. The result may have important implications in developing adult TB vaccine. PMID:25995039

  8. New strain of mouse hepatitis virus as the cause of lethal enteritis in infant mice.

    PubMed Central

    Hierholzer, J C; Broderson, J R; Murphy, F A

    1979-01-01

    A new strain of mouse hepatitis virus (MHV) was isolated from pooled gut suspensions from an epizootic of lethal enteritis in newborn mice. Negative-contrast electron microscopy showed an abundance of coronavirus particles in the intestinal contents and intestinal epithelium of moribund mice. We found no other virus in the epizootic. Dams seroconverted to MHV polyvalent antigen and to the agent isolated, but did not develop antibodies to other known mouse pathogens. Virus propagated in NCTC-1469 tissue culture produced enteric disease in suckling mice but not fatal diarrhea; the dams of these mice also developed antibodies to MHV and to the isolates. By complement fixation, single radial hemolysis, and quantal neutralization tests, we found the isolates antigenically most closely related to MHV-S, unilaterally related to MHV-JHM, and more distantly related to MHV-1, MHV-3, MHV-A59, and human coronavirus OC-43. We also studied cross-reactions among the murine and human coronaviruses in detail. Tissues of infected newborn mice were examined by light microscopy, thin-section electron microscopy, and frozen-section indirect immunofluorescence, revealing that viral antigen, virus particles, and pathological changes were limited to the intestinal tract. We have designated our isolates as MHV-S/CDC. Images PMID:222687

  9. Antibacterial activity of extracellular compounds produced by a Pseudomonas strain against methicillin-resistant Staphylococcus aureus (MRSA) strains

    PubMed Central

    2013-01-01

    Background The emergence of multidrug-resistant bacteria is a world health problem. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains, is one of the most important human pathogens associated with hospital and community-acquired infections. The aim of this work was to evaluate the antibacterial activity of a Pseudomonas aeruginosa-derived compound against MRSA strains. Methods Thirty clinical MRSA strains were isolated, and three standard MRSA strains were evaluated. The extracellular compounds were purified by vacuum liquid chromatography. Evaluation of antibacterial activity was performed by agar diffusion technique, determination of the minimal inhibitory concentration, curve of growth and viability and scanning electron microscopy. Interaction of an extracellular compound with silver nanoparticle was studied to evaluate antibacterial effect. Results The F3 (ethyl acetate) and F3d (dichloromethane- ethyl acetate) fractions demonstrated antibacterial activity against the MRSA strains. Phenazine-1-carboxamide was identified and purified from the F3d fraction and demonstrated slight antibacterial activity against MRSA, and synergic effect when combined with silver nanoparticles produced by Fusarium oxysporum. Organohalogen compound was purified from this fraction showing high antibacterial effect. Using scanning electron microscopy, we show that the F3d fraction caused morphological changes to the cell wall of the MRSA strains. Conclusions These results suggest that P. aeruginosa-produced compounds such as phenazines have inhibitory effects against MRSA and may be a good alternative treatment to control infections caused by MRSA. PMID:23773484

  10. Cyclopean gauge factor of the strain-resistance transduction of indium oxide films

    NASA Astrophysics Data System (ADS)

    Ivančo, J.; Halahovets, Y.; Végsö, K.; Klačková, I.; Kotlár, M.; Vojtko, A.; Micuśík, M.; Jergel, M.; Majková, E.

    2016-03-01

    The resistance of indium-oxide covered polyethylene terephthalate foils (IO-PET) shows an extreme sensitivity to tensile strain. In terms of the deformation-resistance transduction, the gauge factor as high as about 60 000 was recorded upon the relative elongation up to 1%. Except the onset of deformation, the nearly exponential dependence of the resistance on strain suggests that the conductivity of the strained films is governed by tunnelling mechanism; this notion is supported by the formation of scattered cracks in the IO- PET film. The cracks are oriented perpendicularly to the strain vector and are characterized by a rather similar and uniform width. Appropriateness of the standard definition of the gauge factor for strain sensors, which are governed by tunnelling conductance, is critically discussed.

  11. Antibiotic Resistances of Starter and Probiotic Strains of Lactic Acid Bacteria▿

    PubMed Central

    Hummel, Anja S.; Hertel, Christian; Holzapfel, Wilhelm H.; Franz, Charles M. A. P.

    2007-01-01

    The antibiotic resistances of 45 lactic acid bacteria strains belonging to the genera Lactobacillus, Streptococcus, Lactococcus, Pediococcus, and Leuconostoc were investigated. The objective was to determine antibiotic resistances and to verify these at the genetic level, as is currently suggested by the European “qualified presumption of safety” safety evaluation system for industrial starter strains. In addition, we sought to pinpoint possible problems in resistance determinations. Primers were used to PCR amplify genes involved in β-lactam antibiotic, chloramphenicol, tetracycline, and erythromycin resistance. The presence of ribosomal protection protein genes and the ermB gene was also determined by using a gene probe. Generally, the incidences of erythromycin, chloramphenicol, tetracycline, or β-lactam resistances in this study were low (<7%). In contrast, aminoglycoside (gentamicin and streptomycin) and ciprofloxacin resistances were higher than 70%, indicating that these may constitute intrinsic resistances. The genetic basis for ciprofloxacin resistance could not be verified, since no mutations typical of quinolone resistances were detected in the quinolone determining regions of the parC and gyrA genes. Some starter strains showed low-level ampicillin, penicillin, chloramphenicol, and tetracycline resistances, but no known resistance genes could be detected. Although some strains possessed the cat gene, none of these were phenotypically resistant to chloramphenicol. Using reverse transcription-PCR, these cat genes were shown to be silent under both inducing and noninducing conditions. Only Lactobacillus salivarius BFE 7441 possessed an ermB gene, which was encoded on the chromosome and which could not be transferred in filter-mating experiments. This study clearly demonstrates problems encountered with resistance testing, in that the breakpoint values are often inadequately identified, resistance genes may be present but silent, and the genetic basis

  12. Role for Lyt-2+ T cells in resistance to cutaneous leishmaniasis in immunized mice

    SciTech Connect

    Farrell, J.P.; Muller, I.; Louis, J.A.

    1989-03-15

    The role of Lyt-2+ T cells in immunologic resistance to cutaneous leishmaniasis was analyzed by comparing infection patterns in resistant C57BL/6 mice and susceptible BALB/c mice induced to heal their infections after sub-lethal irradiation or i.v. immunization, with similar mice treated in vivo with anti-Lyt-2 antibodies. Administration of anti-Lyt-2 mAb resulted in a dramatic reduction in the number of lymphoid cells expressing the Lyt-2+ phenotype. Such treatment led to enhanced disease in both resistant C57BL/6 and irradiated BALB/c mice, as assessed by lesion size, but did not affect the capacity of these mice to ultimately resolve their infections. In contrast, anti-Lyt-2 treatment totally blocked the induction of resistance in i.v. immunized mice. These results suggest, that Lyt-2+ T cells may play a role in immunity to a Leishmania major infection and that their relative importance to resistance may depend on how resistance is induced.

  13. Comparison of activity to stimulate mucosal IgA production between Leuconostoc mesenteroides strain NTM048 and type strain JCM6124 in mice

    PubMed Central

    MATSUZAKI, Chiaki; MATSUMOTO, Kenji; KATOH, Toshihiko; YAMAMOTO, Kenji; HISA, Keiko

    2015-01-01

    The effects of Leuconostoc mesenteroides strain NTM048 and type strain JCM6124T on the murine immune system were characterized. Although the bacterial cells and exopolysaccharides of each strain induced immunoglobulin A production in Peyer’s patch cells, the effects of NTM048 were more potent than those of JCM6124T. Oral administration of the cells of each strain increased the fecal immunoglobulin A content in NTM048-treated mice, but not in JCM6124T-treated mice. A flow cytometric analysis showed that the CD4+ T-cell populations in the mouse spleens tended to increase in the NTM048 group. These results suggest that immunomodulating ability is characteristic of strain NTM048. PMID:26858930

  14. Genes from Chagas Susceptibility Loci That Are Differentially Expressed in T. cruzi-Resistant Mice Are Candidates Accounting for Impaired Immunity

    PubMed Central

    Graefe, Sebastian E. B.; Streichert, Thomas; Budde, Birgit S.; Nürnberg, Peter; Steeg, Christiane; Müller-Myhsok, Bertram; Fleischer, Bernhard

    2006-01-01

    Variation between inbred mice of susceptibility to experimental Trypanosoma cruzi infection has frequently been described, but the immunogenetic background is poorly understood. The outcross of the susceptible parental mouse strains C57BL/6 (B6) and DBA/2 (D2), B6D2F1 (F1) mice, is highly resistant to this parasite. In the present study we show by quantitative PCR that the increase of tissue parasitism during the early phase of infection is comparable up to day 11 between susceptible B6 and resistant F1 mice. A reduction of splenic parasite burdens occurs thereafter in both strains but is comparatively retarded in susceptible mice. Splenic microarchitecture is progressively disrupted with loss of follicles and B lymphocytes in B6 mice, but not in F1 mice. By genotyping of additional backcross offspring we corroborate our earlier findings that susceptibility maps to three loci on Chromosomes 5, 13 and 17. Analysis of gene expression of spleen cells from infected B6 and F1 mice with microarrays identifies about 0.3% of transcripts that are differentially expressed. Assuming that differential susceptibility is mediated by altered gene expression, we propose that the following differentially expressed transcripts from these loci are strong candidates for the observed phenotypic variation: H2-Eα, H2-D1, Ng23, Msh5 and Tubb5 from Chromosome 17; and Cxcl11, Bmp2k and Spp1 from Chromosome 5. Our results indicate that innate mechanisms are not of primary relevance to resistance of F1 mice to T. cruzi infection, and that differential susceptibility to experimental infection with this protozoan pathogen is not paralleled by extensive variation of the transcriptome. PMID:17183687

  15. Studies of resistance to anticoccidials in Eimeria field isolates and pure Eimeria strains.

    PubMed

    Stephen, B; Rommel, M; Daugschies, A; Haberkorn, A

    1997-04-01

    Ten Eimeria field isolates from North Germany were studied in battery tests for sensitivity to selected anticoccidials. A high percentage of the Eimeria field isolates (9 out of 10) showed resistance to anticoccidials, mostly multiple resistance. Partial or complete resistance to maduramicin was found in 7 field isolates, to monensin in 6, to salinomycin in 5, to nicarbazin in 8, to halofuginone in 7, to robenidine and toltrazuril in 1, and to diclazuril in 2 field isolates. Multiple resistance had developed in 7 of the 10 isolates. Cross-resistance between maduramicin, monensin, and salinomycin occurred in 5 Eimeria isolates. One isolate showed cross-resistance between diclazuril and toltrazuril. From the resistant isolates 15 pure E. acerculina and 5 pure E. brunetti strains were obtained by single oocyst infections. Seven of the E. acerculina and 4 of the E. brunetti strains showed resistance or partial resistance that was also present in the original isolate. Ten of 11 resistant strains were multiply resistant. PMID:9187026

  16. Prevention of Mycobacterium avium subsp. paratuberculosis Infection in BALB/c Mice by Feeding Lactobacillus acidophilus Strain NP-51

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The immune responses of 390 BALB/c mice fed the probiotic Lactobacillus acidophilus strain NP51® and infected with Mycobacterium avium subspecies paratuberculosis (MAP) were evaluated in a 6-month trial. Mice were randomized to nine treatment groups fed either viable- or heat-killed NP51 and inocula...

  17. Isolation of an oxalate-resistant Ashbya gossypii strain and its improved riboflavin production.

    PubMed

    Sugimoto, Takashi; Morimoto, Aki; Nariyama, Masashi; Kato, Tatsuya; Park, Enoch Y

    2010-01-01

    An oxalate-resistant strain of Ashbya gossypii was naturally isolated from spores grown on an oxalate-containing medium, and its medium was optimized to improve riboflavin production. Riboflavin production by the resistant strain was three-fold higher than that by the wild-type organism when grown in flask cultures. Medium optimization increased the riboflavin production by the resistant strain to 5 g l(-1), which was five-fold higher than that obtained by the wild-type strain. The productivity was reproduced in a 3-l bioreactor. During the early growth phase, the specific activity of isocitrate lyase in the oxalate-resistant strain was slightly higher than that in the wild-type strain. Proteomic analysis of the oxalate-resistant strain revealed that the expression of aldose reductase and cobalamin-independent methionine synthase decreased significantly. This is the first report that describes the natural isolation of a riboflavin producer using an antimetabolite-containing medium to enhance the riboflavin production level. This method should also be useful for improving the productivity of other bioproducts since it does not require any mutations or genetic modifications of the microorganism. PMID:19826846

  18. Complete genome sequence of an attenuated Sparfloxacin resistant Streptococcus agalactiae strain 138spar

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Through selection of resistance to sparfloxacin, an attenuated Streptococcus agalactiae strain 138spar was obtained from its virulent parent strain S. agalactiae 138P. The full genome of S. agalactiae 138spar is 1,838,126 bp. The availability of this genome will allow comparative genomics to identi...

  19. RADIATION-RESISTANT FIBER OPTIC STRAIN SENSORS FOR SNS TARGET INSTRUMENTATION

    SciTech Connect

    Blokland, Willem; Bryan, Jeff; Riemer, Bernie; Sangrey, Robert L; Wendel, Mark W; Liu, Yun

    2016-01-01

    Measurement of stresses and strains in the mercury tar-get vessel of the Spallation Neutron Source (SNS) is important to understand the structural dynamics of the target. This work reports the development of radiation-resistant fiber optic strain sensors for the SNS target in-strumentation.

  20. Multidisciplinary Analysis of a Nontoxigenic Clostridium difficile Strain with Stable Resistance to Metronidazole

    PubMed Central

    Moura, Ines; Monot, Marc; Tani, Chiara; Barbanti, Fabrizio; Norais, Nathalie; Dupuy, Bruno; Bouza, Emilio; Mastrantonio, Paola

    2014-01-01

    Stable resistance to metronidazole in a nontoxigenic Clostridium difficile strain was investigated at both the genomic and proteomic levels. Alterations in the metabolic pathway involving the pyruvate-ferredoxin oxidoreductase were found, suggesting that reduction of metronidazole, required for its activity, may be less efficient in this strain. Proteomic studies also showed a cellular response to oxidative stress. PMID:24913157

  1. Multidisciplinary analysis of a nontoxigenic Clostridium difficile strain with stable resistance to metronidazole.

    PubMed

    Moura, Ines; Monot, Marc; Tani, Chiara; Spigaglia, Patrizia; Barbanti, Fabrizio; Norais, Nathalie; Dupuy, Bruno; Bouza, Emilio; Mastrantonio, Paola

    2014-08-01

    Stable resistance to metronidazole in a nontoxigenic Clostridium difficile strain was investigated at both the genomic and proteomic levels. Alterations in the metabolic pathway involving the pyruvate-ferredoxin oxidoreductase were found, suggesting that reduction of metronidazole, required for its activity, may be less efficient in this strain. Proteomic studies also showed a cellular response to oxidative stress. PMID:24913157

  2. Cell-surface alterations in class IIa bacteriocin-resistant Listeria monocytogenes strains.

    PubMed

    Vadyvaloo, Viveka; Arous, Safia; Gravesen, Anne; Héchard, Yann; Chauhan-Haubrock, Ramola; Hastings, John W; Rautenbach, Marina

    2004-09-01

    Strains of the food-borne pathogen Listeria monocytogenes, showing either intermediate or high-level resistance to class IIa bacteriocins, were investigated to determine characteristics that correlated with their sensitivity levels. Two intermediate and one highly resistant spontaneous mutant of L. monocytogenes B73, a highly resistant mutant of L. monocytogenes 412, and a highly resistant, defined (mptA) mutant of L. monocytogenes EGDe were compared with their respective wild-type strains in order to investigate the contribution of different factors to resistance. Decreased mannose-specific phosphotransferase system gene expression (mptA, EIIAB(Man) component) was implicated in all levels of resistance, confirming previous studies by the authors' group. However, a clear correlation between d-alanine content in teichoic acid (TA), in particular the alanine : phosphorus ratio, and a more positive cell surface, as determined by cytochrome c binding, were found for the highly resistant strains. Furthermore, two of the three highly resistant strains showed a significant increase in sensitivity towards d-cycloserine (DCS). However, real-time PCR of the dltA (d-alanine esterification), and dal and ddlA genes (peptidoglycan biosynthesis) showed no change in transcriptional levels. The link between DCS sensitivity and increased d-alanine esterification of TA may be that DCS competes with alanine for transport via the alanine transporter. A possible tendency towards increased lysinylation of membrane phospholipid in the highly resistant strains was also found. A previous study reported that cell membranes of all the resistant strains, including the intermediate resistant strains, contained more unsaturated phosphatidylglycerol, which is an indication of a more fluid cell membrane. The results of that study correlate with the possible lysinylation, decreased mptA expression, d-alanine esterification of TA and more positive cell surface charge found in this study for

  3. The persistence of antibiotic resistance: evaluation of a probiotic approach using antibiotic-sensitive M. elsdenii strains to prevent colonization of swine by antibiotic-resistant strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Megasphaera elsdenii is a lactate-fermenting, obligately anaerobic bacterium commonly present in the gastrointestinal tracts of mammals, including humans. Swine M. elsdenii strains were previously shown to have high levels of tetracycline resistance (MIC = 64->256 micro g/ml) and to carry mosaic (re...

  4. Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors.

    PubMed

    Fišerová, Anna; Richter, Jan; Čapková, Katarína; Bieblová, Jana; Mikyšková, Romana; Reiniš, Milan; Indrová, Marie

    2016-08-01

    To elucidate the immunological mechanisms critical for tumor progression, we bred novel mouse strains, different in the NKC and H-2D domains. We used inbreeding to generate hybrids of Balb/c and C57BL/6 of stable H-2Db+d-NK1.1neg and H-2Db-d+NK1.1high phenotypes. We analyzed the growth of three established MHC class I-deficient tumor cell lines: TC-1/A9 tumor (HPV-associated) and B16F10 melanoma, both syngeneic to C57BL/6, and the MCB8 (3-methycholanthrene-induced tumor) syngeneic to Balb/c. Furthermore, we induced colorectal carcinoma by azoxymethane-DSS treatment to test the susceptibility to chemically-induced primary cancer. We found that the novel strains spontaneously regressed the tumor transplants syngeneic to both Balb/c (MCB8) and C57BL/6 (B16F10 and TC-1/A9) mice. The H2-Db+d-NK1.1neg, but not the H2-Db-d+NK1.1high strain was also highly resistant to chemically-induced colorectal cancer in comparison to the parental mice. The immune changes during TC-1/A9 cancer development involved an increase of the NK cell distribution in the peripheral blood and spleen along with higher expression of NKG2D activation antigen; this was in correlation with the time-dependent rise of cytotoxic activity in comparison to C57BL/6 mice. The TC-1/A9 cancer regression was accompanied by higher proportion of B cells in the spleen and B220+/CD86+ activated antigen-presenting B cells distributed in the lymphoid organs, as well as in the periphery. The changes in the T-cell population were represented mainly by the prevalence of T helper cells reflected by grown CD4/CD8 ratio, most prominent in the b+d-NK1.1neg strain. The results of the present study imply usefulness of the two novel mouse strains as an experimental model for further studies of tumor resistance mechanisms. PMID:27279019

  5. Antibiotic Resistance Determinants in a Pseudomonas putida Strain Isolated from a Hospital

    PubMed Central

    Duque, Estrella; Fernández, Matilde; Molina-Santiago, Carlos; Roca, Amalia; Porcel, Mario; de la Torre, Jesús; Segura, Ana; Plesiat, Patrick; Jeannot, Katy; Ramos, Juan-Luis

    2014-01-01

    Environmental microbes harbor an enormous pool of antibiotic and biocide resistance genes that can impact the resistance profiles of animal and human pathogens via horizontal gene transfer. Pseudomonas putida strains are ubiquitous in soil and water but have been seldom isolated from humans. We have established a collection of P. putida strains isolated from in-patients in different hospitals in France. One of the isolated strains (HB3267) kills insects and is resistant to the majority of the antibiotics used in laboratories and hospitals, including aminoglycosides, ß-lactams, cationic peptides, chromoprotein enediyne antibiotics, dihydrofolate reductase inhibitors, fluoroquinolones and quinolones, glycopeptide antibiotics, macrolides, polyketides and sulfonamides. Similar to other P. putida clinical isolates the strain was sensitive to amikacin. To shed light on the broad pattern of antibiotic resistance, which is rarely found in clinical isolates of this species, the genome of this strain was sequenced and analysed. The study revealed that the determinants of multiple resistance are both chromosomally-borne as well as located on the pPC9 plasmid. Further analysis indicated that pPC9 has recruited antibiotic and biocide resistance genes from environmental microorganisms as well as from opportunistic and true human pathogens. The pPC9 plasmid is not self-transmissible, but can be mobilized by other bacterial plasmids making it capable of spreading antibiotic resistant determinants to new hosts. PMID:24465371

  6. Antibiotic resistance determinants in a Pseudomonas putida strain isolated from a hospital.

    PubMed

    Molina, Lázaro; Udaondo, Zulema; Duque, Estrella; Fernández, Matilde; Molina-Santiago, Carlos; Roca, Amalia; Porcel, Mario; de la Torre, Jesús; Segura, Ana; Plesiat, Patrick; Jeannot, Katy; Ramos, Juan-Luis

    2014-01-01

    Environmental microbes harbor an enormous pool of antibiotic and biocide resistance genes that can impact the resistance profiles of animal and human pathogens via horizontal gene transfer. Pseudomonas putida strains are ubiquitous in soil and water but have been seldom isolated from humans. We have established a collection of P. putida strains isolated from in-patients in different hospitals in France. One of the isolated strains (HB3267) kills insects and is resistant to the majority of the antibiotics used in laboratories and hospitals, including aminoglycosides, ß-lactams, cationic peptides, chromoprotein enediyne antibiotics, dihydrofolate reductase inhibitors, fluoroquinolones and quinolones, glycopeptide antibiotics, macrolides, polyketides and sulfonamides. Similar to other P. putida clinical isolates the strain was sensitive to amikacin. To shed light on the broad pattern of antibiotic resistance, which is rarely found in clinical isolates of this species, the genome of this strain was sequenced and analysed. The study revealed that the determinants of multiple resistance are both chromosomally-borne as well as located on the pPC9 plasmid. Further analysis indicated that pPC9 has recruited antibiotic and biocide resistance genes from environmental microorganisms as well as from opportunistic and true human pathogens. The pPC9 plasmid is not self-transmissible, but can be mobilized by other bacterial plasmids making it capable of spreading antibiotic resistant determinants to new hosts. PMID:24465371

  7. New Ceftriaxone- and Multidrug-Resistant Neisseria gonorrhoeae Strain with a Novel Mosaic penA Gene Isolated in Japan.

    PubMed

    Nakayama, Shu-Ichi; Shimuta, Ken; Furubayashi, Kei-Ichi; Kawahata, Takuya; Unemo, Magnus; Ohnishi, Makoto

    2016-07-01

    We have characterized in detail a new ceftriaxone- and multidrug-resistant Neisseria gonorrhoeae strain (FC428) isolated in Japan in 2015. FC428 differed from previous ceftriaxone-resistant strains and contained a novel mosaic penA allele encoding a new mosaic penicillin-binding protein 2 (PBP 2). However, the resistance-determining 3'-terminal region of penA was almost identical to the regions of two previously reported ceftriaxone-resistant strains from Australia and Japan, indicating that both ceftriaxone-resistant strains and conserved ceftriaxone resistance-determining PBP 2 regions might spread. PMID:27067334

  8. Strain differences in the attenuation of bone accrual in a young growing mouse model of insulin resistance.

    PubMed

    Rendina-Ruedy, Elizabeth; Graef, Jennifer L; Davis, McKale R; Hembree, Kelsey D; Gimble, Jeffrey M; Clarke, Stephen L; Lucas, Edralin A; Smith, Brenda J

    2016-07-01

    Skeletal fractures are considered a chronic complication of type 2 diabetes mellitus (T2DM), but the etiology of compromised bone quality that develops over time remains uncertain. This study investigated the concurrent alterations in metabolic and skeletal changes in two mouse strains, a responsive (C57BL/6) and a relatively resistant (C3H/HeJ) strain, to high-fat diet-induced glucose intolerance. Four-week-old male C57BL/6 and C3H/HeJ mice were randomized to a control (Con = 10 % kcal fat) or high-fat (HF = 60 % kcal fat) diet for 2, 8, or 16 weeks. Metabolic changes, including blood glucose, plasma insulin and leptin, and glucose tolerance were monitored over time in conjunction with alterations in bone structure and turn over. Elevated fasting glucose occurred in both the C57BL/6 and C3H/HeJ strains on the HF diet at 2 and 8 weeks, but only in the C57BL/6 strain at 16 weeks. Both strains on the HF diet demonstrated impaired glucose tolerance at each time point. The C57BL/6 mice on the HF diet exhibited lower whole-body bone mineral density (BMD) by 8 and 16 weeks, but the C3H/HeJ strain had no evidence of bone loss until 16 weeks. Analyses of bone microarchitecture revealed that trabecular bone accrual in the distal femur metaphysis was attenuated in the C57BL/6 mice on the HF diet at 8 and 16 weeks. In contrast, the C3H/HeJ mice were protected from the deleterious effects of the HF diet on trabecular bone. Alterations in gene expression from the femur revealed that several toll-like receptor (TLR)-4 targets (Atf4, Socs3, and Tlr4) were regulated by the HF diet in the C57BL/6 strain, but not in the C3H/HeJ strain. Structural changes observed only in the C57BL/6 mice were accompanied with a decrease in osteoblastogenesis after 8 and 16 weeks on the HF diet, suggesting a TLR-4-mediated mechanism in the suppression of bone formation. Both the C57BL/6 and C3H/HeJ mice demonstrated an increase in osteoclastogenesis after 8 weeks on the HF diet; however

  9. Liver lobe and strain difference in gene expression after hydrodynamics-based gene delivery in mice.

    PubMed

    Nakamura, Shingo; Maehara, Tadaaki; Watanabe, Satoshi; Ishihara, Masayuki; Sato, Masahiro

    2015-01-01

    Hydrodynamics-based gene delivery (HGD) is a widely recognized technique for delivering exogenous DNA with high efficiency to murine hepatocytes. In this study, we investigated stimulation of exogenous DNA uptake and expression using a commercially available reagent for HGD. We also examined which mouse strain and mouse liver lobe would achieve the best gene delivery performance. Mice were injected with a solution containing reporter plasmid DNA or DNA and a gene delivery reagent. One day after the HGD procedure, liver samples were isolated and subjected to biochemical and histochemical analyses. The reporter plasmid DNA showed the strongest signal when the DNA was dissolved in TransIT-EE Hydrodynamic Delivery Solution (Takara Bio Inc., Shiga, Japan). Evaluation of transgene expression in each hepatic lobe in ICR, C57BL/6N, Balb/cA, and B6C3F1 mice showed that ICR mice exhibited the best gene transfer and that the right median lobe had the highest level of transgene expression. These findings suggest the importance of choice in mouse strains and liver lobes when performing gene-based manipulations of the liver. PMID:25153456

  10. Activity of faropenem tested against Neisseria gonorrhoeae isolates including fluoroquinolone-resistant strains.

    PubMed

    Jones, Ronald N; Critchley, Ian A; Whittington, William L H; Janjic, Nebojsa; Pottumarthy, Sudha

    2005-12-01

    We evaluated the anti-gonococcal potency of faropenem along with 7 comparator reference antimicrobials against a preselected collection of clinical isolates. The 265 isolates were inclusive of 2 subsets: 1) 76 well-characterized resistant phenotypes of gonococcal strains (53 quinolone-resistant strains--31 with documented quinolone resistance-determining region changes from Japan, 15 strains resistant to penicillin and tetracycline, and 8 strains with intermediate susceptibility to penicillin) and 2) 189 recent isolates from clinical specimens in 2004 from 6 states across the United States where quinolone resistance is prevalent. Activity of faropenem was adversely affected by l-cysteine hydrochloride in IsoVitaleX (4-fold increase in [minimal inhibitory concentration] MIC50; 0.06 versus 0.25 microg/mL). The rank order of potency of the antimicrobials for the entire collection was ceftriaxone (MIC90, 0.06 microg/mL) > faropenem (0.25 microg/mL) > azithromycin (0.5 microg/mL) > cefuroxime (1 microg/mL) > tetracycline (2 microg/mL) > penicillin = ciprofloxacin = levofloxacin (4 microg/mL). Using MIC90 for comparison, faropenem was 4-fold more potent than cefuroxime (0.25 versus 1 microg/mL), but was 4-fold less active than ceftriaxone (0.25 versus 0.06 microg/mL). Although the activity of faropenem was not affected by either penicillinase production (MIC90, 0.12 microg/mL, penicillinase-positive) or increasing ciprofloxacin MIC (0.25 microg/mL, ciprofloxacin-resistant), increasing penicillin MIC was associated with an increase in MIC90 values (0.016 microg/mL for penicillin-susceptible to 0.25 microg/mL for penicillin-resistant strains). Among the recent (2004) clinical gonococcal isolates tested, reduced susceptibility to penicillins, tetracycline, and fluoroquinolones was high (28.0-94.2%). Geographic distribution of the endemic resistance rates of gonococci varied considerably, with 16.7-66.7% of the gonococcal isolates being ciprofloxacin-resistant in Oregon

  11. Compensatory Mutations of Rifampin Resistance Are Associated with Transmission of Multidrug-Resistant Mycobacterium tuberculosis Beijing Genotype Strains in China.

    PubMed

    Li, Qin-Jing; Jiao, Wei-Wei; Yin, Qing-Qin; Xu, Fang; Li, Jie-Qiong; Sun, Lin; Xiao, Jing; Li, Ying-Jia; Mokrousov, Igor; Huang, Hai-Rong; Shen, A-Dong

    2016-05-01

    Mycobacterium tuberculosis can acquire resistance to rifampin (RIF) through mutations in the rpoB gene. This is usually accompanied by a fitness cost, which, however, can be mitigated by secondary mutations in the rpoA or rpoC gene. This study aimed to identify rpoA and rpoC mutations in clinical M. tuberculosis isolates in northern China in order to clarify their role in the transmission of drug-resistant tuberculosis (TB). The study collection included 332 RIF-resistant and 178 RIF-susceptible isolates. The majority of isolates belonged to the Beijing genotype (95.3%, 486/510 isolates), and no mutation was found in rpoA or rpoC of the non-Beijing genotype strains. Among the Beijing genotype strains, 27.8% (89/320) of RIF-resistant isolates harbored nonsynonymous mutations in the rpoA (n = 6) or rpoC (n = 83) gene. The proportion of rpoC mutations was significantly higher in new cases (P = 0.023) and in strains with the rpoB S531L mutation (P < 0.001). In addition, multidrug-resistant (MDR) strains with rpoC mutations were significantly associated with 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat clustering (P = 0.016). In summary, we believe that these findings indirectly suggest an epistatic interaction of particular mutations related to RIF resistance and strain fitness and, consequently, the role of such mutations in the spread of MDR M. tuberculosis strains. PMID:26902762

  12. Antimicrobial Susceptibility and Resistance Patterns among Helicobacter pylori Strains from The Gambia, West Africa

    PubMed Central

    Berg, Douglas E.; Antonio, Martin; Corrah, Tumani; Tapgun, Mary; Walton, Robert; Thomas, Vivat; Galano, Juan J.; Sancho, Javier; Adegbola, Richard A.; Thomas, Julian E.

    2013-01-01

    Helicobacter pylori is a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Eradication efforts are complicated by antibiotic resistance, which varies in frequency geographically. There are very few data on resistance in African strains. Sixty-four Gambian H. pylori strains were tested for antibiotic susceptibility. The role of rdxA in metronidazole (Mtz) susceptibility was tested by DNA transformation and sequencing; RdxA protein variants were interpreted in terms of RdxA structure. Forty-four strains (69%) were resistant to at least 8 μg of Mtz/ml. All six strains from infants, but only 24% of strains from adults, were sensitive (P = 0.0031). Representative Mtz-resistant (Mtzr) strains were rendered Mtz susceptible (Mtzs) by transformation with a functional rdxA gene; conversely, Mtzs strains were rendered Mtzr by rdxA inactivation. Many mutations were found by Gambian H. pylori rdxA sequencing; mutations that probably inactivated rdxA in Mtzr strains were identified and explained using RdxA protein's structure. All of the strains were sensitive to clarithromycin and erythromycin. Amoxicillin and tetracycline resistance was rare. Sequence analysis indicated that most tetracycline resistance, when found, was not due to 16S rRNA gene mutations. These data suggest caution in the use of Mtz-based therapies in The Gambia. The increasing use of macrolides against respiratory infections in The Gambia calls for continued antibiotic susceptibility monitoring. The rich variety of rdxA mutations that we found will be useful in further structure-function studies of RdxA, the enzyme responsible for Mtz susceptibility in this important pathogen. PMID:23263004

  13. Implication of phagosome-lysosome fusion in restriction of Mycobacterium avium growth in bone marrow macrophages from genetically resistant mice.

    PubMed Central

    de Chastellier, C; Fréhel, C; Offredo, C; Skamene, E

    1993-01-01

    The ability of the host to resist infection to a variety of intracellular pathogens, including mycobacteria, is strongly dependent upon the expression of the Bcg gene. Mouse strains which express the resistance phenotype (Bcgr) restrict bacterial growth, whereas susceptible strains (Bcgs) allow bacterial growth. Expression of the Bcg allele is known to influence the priming of host macrophages (M phi s) for bactericidal function. In the present work, bone marrow-derived M phi s from congenic BALB/c (Bcgs) and C.D2 (BALB/c.Bcgr) mice were infected with the virulent strain Mycobacterium avium TMC 724 to define the mechanism involved in growth restriction of M. avium. By combining CFU measurements and ultrastructural analyses, we show that growth of this bacterium is restricted in marrow M phi s from resistant mice. Using acid phosphatase as a lysosomal marker, we provide evidence that the hydrolytic activity of M phi s, as measured by the capacity of lysosomes to fuse with and transfer active hydrolytic enzymes to phagosomes in which M. avium resides, is an expression of the Bcg gene and that this phenomenon is a key antibacterial activity responsible for growth restriction of M. avium: (i) the percentage of phagosome-lysosome fusions was twice as high in Bcgr M phi s as in Bcgs M phi s, and (ii) the percentage of intact viable bacteria residing in acid phosphatase-negative phagosomes was twice as low in Bcgr M phi s as in the Bcgs counterparts. These differences are not due to a lower activity of the enzyme in Bcgr M phi s. The mechanism by which the Bcg gene exerts control over the phagolysosomal fusion is discussed. Images PMID:8359899

  14. Determination of Three-Dimensional Ventricular Strain Distributions in Gene-Targeted Mice Using Tagged MRI

    PubMed Central

    Chuang, Joyce S.; Zemljic-Harpf, Alice; Ross, Robert S.; Frank, Lawrence R.; McCulloch, Andrew D.; Omens, Jeffrey H.

    2012-01-01

    A model-based method for calculating three-dimensional (3D) cardiac wall strain distributions in the mouse has been developed and tested in a genetically engineered mouse model of dilated cardiomyopathy. Data from MR tagging and harmonic phase (HARP) tracking were used to measure material point displacements, and 3D Lagrangian strains were calculated throughout the entire left ventricle (LV) with a deformable parametric model. A mouse model where cardiomyocytes are specifically made deficient in vinculin (VclKO) were compared to wild-type (WT) littermates. 3D strain analysis revealed differences in LV wall mechanics between WT and VclKO mice at 8 weeks of age when systolic function had just begun to decline. Most notably, end-systolic radial strain and torsional shear were reduced in VclKO hearts which contributed to regional mechanical dysfunction. This study demonstrates the feasibility of using MRI tagging methods to detect alterations in 3D myocardial strain distributions in genetically engineered mouse models of cardiovascular disease. PMID:20981782

  15. Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3int B220+ γδ T cells with double-negative CD4 − CD8− phenotype in the liver

    PubMed Central

    Bakir, Hanaa Y; Tomiyama-Miyaji, Chikako; Watanabe, Hisami; Nagura, Toru; Kawamura, Toshihiko; Sekikawa, Hiroho; Abo, Toru

    2006-01-01

    DBA/2 (H-2d) mice are known to be more resistant than C57BL/6 (B6, H-2b) mice to the non-lethal 17XNL strain of Plasmodium yoelii. This is a very strange phenomenon because the functions of conventional T cells, especially CD8+ T cells, are known to be somewhat lower in DBA/2 mice than in other strains of mice. We examined herein how immune responses differed between DBA/2 mice and B6 mice during malarial infection. DBA/2 mice and (DBA/2 × B6)F1 (BDF1, H-2b/d) mice were found to have milder parasitaemia and to recover more quickly from malarial infection than B6 mice. These DBA/2 and BDF1 mice were also found to experience a marked expansion of interleukin (IL)-2Rβ+ CD3int cells and γδ T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220+ T cells) was also marked in DBA/2 and BDF1 mice. The majority of B220+ T cells were γδ T cells and these T cells were double-negative CD4− CD8−. More importantly, the production of immunoglobulin M (IgM)-type anti-DNA autoantibody was also higher in DBA/2 and BDF1 mice than in B6 mice. In conjunction with data on cytokine production, these results indicate that primitive T and B cells, namely autoreactive extrathymic T cells and autoantibody-producing B cells, may be much more activated in DBA/2 mice and therefore resistant to the non-lethal 17XNL strain of P. yoelii. PMID:16423048

  16. HOST RESISTANCE TO MURINE MALARIA IN MICE EXPOSED TO THE ADENOSINE TEAMINASE INHIBITOR, 2'-DEOXYCOFORMYCIN

    EPA Science Inventory

    Resistance to infection with the nonlethal rodent malaria parasite Plasmodium yoelii 17XNL is mediated by humoral, T-cell and accessory cell activity. he purpose of this study was to profile host resistance to infection with this organism in mice xposed to 2'-deoxycoformycin (2dC...

  17. Genome Sequence of Riemerella anatipestifer Strain RCAD0122, a Multidrug-Resistant Isolate from Ducks

    PubMed Central

    Song, Xiao-Heng; Zhou, Wang-Shu; Wang, Jiang-Bo; Liu, Ma-Feng; Wang, Ming-Shu; Cheng, An-Chun; Jia, Ren-Yong; Chen, Shun; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Chen, Xiao-Yue

    2016-01-01

    Riemerella anatipestifer is an important pathogenic bacterium in waterfowl and other avian species. We present here the genome sequence of R. anatipestifer RCAD0122, a multidrug-resistant strain isolated from infected ducks. The isolate contains at least nine types of antibiotic resistance-associated genes. PMID:27151800

  18. Campylobacter coli naturally resistant to elevated levels of gentamicin as a marker strain in poultry research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inoculation studies with Campylobacter are limited without a suitable marker. The purpose of the study was to screen Campylobacter strains (n>2,000) obtained from poultry carcass rinses through the National Antimicrobial Resistant Monitoring System (NARMS) for resistance to gentamicin and evaluate ...

  19. Antimicrobial edible apple films inactivate antibiotic resistant and susceptible Campylobacter jejuni strains on chicken breast

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter jejuni is the leading cause of bacterial diarrheal illness worldwide. Many strains are now becoming multi-drug resistant. To help overcome this problem, apple-based edible films containing carvacrol and cinnamaldehyde were evaluated for their effectiveness against antibiotic resistant...

  20. [Resistance to fluoroquinolone among Klebsiella spp strains producing extended-spectrum betalactamases isolated from urine].

    PubMed

    Tlamçani, Z; Ellaia, K; Benomar, A; Kabbaj, H; Alaoui, Ae; Seffar, M

    2009-01-01

    The aim of the study was to assess the frequency of resistance to fluoroquinolones in extended-spectrum beta-lactamase (ESBLs) Klebsiella spp isolated from urines of consulting and hospitalized patients in Rabat Specialities Hospital. A retrospective survey was made over 3 years (2006-2008). Two hundred ant fifty three patients presented with confirmed urinary tractus infection (UTI). Klebsiella spp was the etiologic agent in 28% (72/253) of reported UTI. Among them, 86% of Klebsiella pneumoniae and 14% of Klebsiella oxytoca. The frequency of Klebsiella spp resistance to fluoroquinolones was 33% and to third generation cephalosporins was 35%. Thirteen Klebsiella spp strains were producing extended-spectrum beta-lactamase witch corresponds to 18% of all the klebsiella. The extended-spectrum beta-lactamase strains with resistance to fluoroquinolones were 85% (11/13) or 15 % of all klebsiella (11/72). None of those strains was resistant to imipenem. In conclusions resistance of enterobacteries such as Klebsiella spp to fluoroquinolones is becoming worrying among consulting and hospitalized patients. Eleven strains multiresistant (ESBL + resistance to fluoroquinolones), isolated probably because of plasmids carrying genes of ESBL and fluoroquinolones resistances. This increasingly frequent resistance mechanism should lead to a more careful use of first line fluoroquinolones for UTI. PMID:19789127

  1. Emergence of Carbapenem-Resistant Serotype K1 Hypervirulent Klebsiella pneumoniae Strains in China

    PubMed Central

    Zhang, Rong; Lin, Dachuan; Chan, Edward Wai-chi; Gu, Danxia

    2015-01-01

    We report the emergence of five carbapenem-resistant K1 hypervirulent Klebsiella pneumoniae (hvKP) strains which caused fatal infections in hospital patients in Zhejiang Province, China, upon entry through surgical wounds. Genotyping results revealed the existence of three genetically related strains which exhibited a new sequence type, ST1797, and revealed that all strains harbored the magA and wcaG virulence genes and a plasmid-borne blaKPC-2 gene. These findings indicate that K1 hvKP is simultaneously hypervirulent, multidrug resistant, and transmissible. PMID:26574010

  2. Contribution of orosensory stimulation to strain differences in oil intake by mice.

    PubMed

    Glendinning, John I; Feld, Natalie; Goodman, Leora; Bayor, Rouane

    2008-10-20

    Little is known about why animals differ in daily intake of oils. Here, we tested the hypothesis that the oral acceptability of oil is a key determinant of daily intake. To this end, we examined short- and long-term ingestive responses of eight mouse strains (FVB/NJ, SWR/J, SM/J, C57BL/6J, BALB/cJ, 129P3/J, DBA/2J and AKR/J) to Intralipid, a stable emulsion of soybean oil. In Experiment 1, we compared orosensory responsiveness (as indicated by initial licking rates) of eight mouse strains to a range of concentrations of Intralipid and sucrose. We included sucrose because there are two natural alleles of Tas1r3 (the gene that encodes the T1R3 sweet taste receptor), and strains with the Tas1r3Sac-b allele exhibit higher daily intake of sucrose and oil than strains with the Tas1r3Sac-d allele. All strains exhibited concentration-dependent increases in lick rates for both sucrose and Intralipid, but the extent of these increases varied greatly across strains. The strains with the Tas1r3Sac-b allele licked more vigorously for sucrose at concentrations < or =0.3 M, but not for Intralipid at any concentration. In Experiment 2, we ran the mice through 24-h preference tests, in which they had a choice between water and each of four concentrations of Intralipid (1, 5, 10 and 20%). The strains differed greatly in daily intake of Intralipid, particularly at the 1 and 5% concentrations. Regression analyses revealed that strain differences in orosensory responsiveness reliably predicted strain differences in daily intake of 1 and 5% Intralipid, but not 10 or 20% Intralipid. These findings indicate (i) that Tas1r3 genotype does not modulate orosensory stimulation from oil, (ii) that orosensory stimulation contributes to strain differences in daily intake of dilute oil emulsions, but not concentrated ones, and (iii) that daily intake of concentrated oil emulsions is controlled primarily by post-oral satiety mechanisms. PMID:18691606

  3. Antimicrobial resistance of 100 Salmonella strains isolated from Gallus gallus in 4 wilayas of Algeria.

    PubMed

    Bounar-Kechih, S; Hamdi, T M; Mezali, L; Assaous, F; Rahal, K

    2012-05-01

    This study aims at identifying serotypes and surveying the antimicrobial resistance and plasmid support of resistance of 100 Salmonella strains, which were isolated from 96 out of 506 (18.97%) samples taken from different production farms in the wilayas (i.e., Algerian states) of Tizi-Ouzou, Bouira, Bejaïa, and Boumerdes in 2007. The highest percentage of Salmonella (48%) was recorded in Bouira. Thirteen serotypes were identified among the 100 Salmonella strains used in this study. The most prevalent ones were Salmonella Heidelberg (24%), Salmonella Enteritidis (20%), Salmonella Albany (16%), and Salmonella Typhimurium (9%). The strains showed resistance to 8 of the 34 antibiotics tested. Fifty-three percent of strains were resistant to at least one antibiotic, among which 15.09% were multiresistant. The most frequently observed resistance was to quinolones (58.49%), with a contribution of 94.74% of Salmonella Heidelberg resistant strains. The plasmid transfer performed on 53 strains showed that only 11 exhibited one or more markers of resistance, the most frequent being ampicillin, followed by tetracycline, then cotrimoxazole, sulphonamides, and kanamycin, in that order. The tetracycline characteristics were present in 72.72% of transconjugants, those of the β-lactams and sulphonamides in 27.27% each and those of the aminosides in 9.09%. The incompatibility groups of plasmids belong to the F1me and Com1 classes, and the molecular weight of the plasmid DNA was greater than 100 kb. The phenotypic and genotypic results indicate a clonal dissemination in the Gallus gallus species in this particular study; this phenomenon could generate resistant bacteria and transferable genes of resistance to humans. PMID:22499877

  4. Association of Nrf2 Polymorphism Haplotypes with Acute Lung Injury Phenotypes in Inbred Strains of Mice

    PubMed Central

    Jedlicka, Anne E.; Gladwell, Wesley; Marzec, Jacqui; McCaw, Zackary R.; Bienstock, Rachelle J.; Kleeberger, Steven R.

    2015-01-01

    Abstract Aims: Nrf2 is a master transcription factor for antioxidant response element (ARE)-mediated cytoprotective gene induction. A protective role for pulmonary Nrf2 was determined in model oxidative disorders, including hyperoxia-induced acute lung injury (ALI). To obtain additional insights into the function and genetic regulation of Nrf2, we assessed functional single nucleotide polymorphisms (SNPs) of Nrf2 in inbred mouse strains and tested whether sequence variation is associated with hyperoxia susceptibility. Results: Nrf2 SNPs were compiled from publicly available databases and by re-sequencing DNA from inbred strains. Hierarchical clustering of Nrf2 SNPs categorized the strains into three major haplotypes. Hyperoxia susceptibility was greater in haplotypes 2 and 3 strains than in haplotype 1 strains. A promoter SNP −103 T/C adding an Sp1 binding site in haplotype 2 diminished promoter activation basally and under hyperoxia. Haplotype 3 mice bearing nonsynonymous coding SNPs located in (1862 A/T, His543Gln) and adjacent to (1417 T/C, Thr395Ile) the Neh1 domain showed suppressed nuclear transactivation of pulmonary Nrf2 relative to other strains, and overexpression of haplotype 3 Nrf2 showed lower ARE responsiveness than overexpression of haplotype 1 Nrf2 in airway cells. Importantly, we found a significant correlation of Nrf2 haplotypes and hyperoxic lung injury phenotypes. Innovation and Conclusion: The results indicate significant influence of Nrf2 polymorphisms and haplotypes on gene function and hyperoxia susceptibility. Our findings further support Nrf2 as a genetic determinant in ALI pathogenesis and provide useful tools for investigators who use mouse strains classified by Nrf2 haplotypes to elucidate the role for Nrf2 in oxidative disorders. Antioxid. Redox Signal. 22, 325–338. PMID:25268541

  5. Interaction of (+)-amphetamine with cerebral dopaminergic neurones in two strains of mice, that show different temperature responses to this drug

    PubMed Central

    Caccia, S.; Cecchetti, G.; Garattini, S.; Jori, A.

    1973-01-01

    1. (+)-Amphetamine sulphate elicits a dose-dependent hyperthermia in NMRI mice but it does not significantly increase the body temperature of C3H mice. 2. When low doses of (+)-amphetamine are given, the body temperature of C3H mice decreases. 3. (+)-Amphetamine decreases the noradrenaline concentration in the brain-stem and increases the homovanillic acid concentration (HVA) in the striatum of NMRI mice, but only slightly reduces the noradrenaline concentration and does not change the HVA concentration in the brains of C3H mice. 4. The two strains appear to show a difference in the metabolism of dopamine in the striatum. The rates at which dopamine disappears from the tissue after blocking catecholamine synthesis with α-methyltyrosine and the rates at which HVA accumulates after blocking the active transport of this metabolite out of the brain with probenecid suggest that the turnover of dopamine is lower in C3H mice than in NMRI mice. PMID:4777703

  6. IS6110 fingerprinting of drug-resistant Mycobacterium tuberculosis strains isolated in Germany during 1995.

    PubMed Central

    Niemann, S; Rüsch-Gerdes, S; Richter, E

    1997-01-01

    The epidemiological relatedness of drug-resistant Mycobacterium tuberculosis strains isolated in Germany in 1995 was evaluated by the standardized IS6110 fingerprinting method. Altogether, 196 M. tuberculosis isolates from 167 patients were analyzed. A large degree of IS6110 polymorphism was found, ranging from 1 to 20 copies. Multiple isolates from one patient generally remained stable over a period of up to 1 year. However, one strain showed an additional fragment 7 months after the first isolate was obtained. Isolates from 55 patients (33%) showed identical fingerprint patterns or fingerprint patterns that differed only in one band, and thus they were clustered in 22 fingerprint groups. Specific transmission links could be established between members of four groups, e.g., transmission by family contacts. In one case, transmission of a multidrug-resistant strain to a patient initially infected with a drug-susceptible strain could be shown. Besides these fingerprint groups, 30 of the 167 isolates (approximately 18%) could be grouped in two fingerprint clusters with a similarity of at least 78%. Approximately 60% of the patients of these two clusters were known to be immigrants from the former Soviet Union, and one patient is still living in Belarus. In conclusion, our results indicate that (i) transmission of drug-resistant strains contributes substantially to the emergence of drug-resistant tuberculosis in Germany and (ii) drug-resistant M. tuberculosis strains were presumably carried over from the former Soviet Union to Germany by immigrants. PMID:9399486

  7. Biofilm production among methicillin resistant Staphylococcus aureus strains isolated from catheterized patients with urinary tract infection.

    PubMed

    Rahimi, Fateh; Katouli, Mohammad; Karimi, Sharmin

    2016-09-01

    Between June 2011 and May 2014, we isolated a total of 419 Staphylococcus aureus strains from catheterized patients with UTI in a referral hospital in Tehran. Of these, 108 were identified as methicillin resistant (MRSA) based on their phenotypic resistance to oxacillin and the presence of mecA gene. The MRSA isolates were tested for their clonality using a combination of PFGE, prophage typing, SCCmec and ccr typing and examined for their biofilm formation as well as their resistance against 17 antibiotics. In all, 15 common pulsotypes consisted of 105 isolates and 3 single types were identified among the MRSA strains of which, 97% carried SCCmec type III and type 3 ccr. Eighty three (77%) strains were positive for biofilm formation and also carried icaA and icaD genes. Moreover, agr group III and its related tst gene were detected in 81% and 77% of biofilm producing strains, respectively 105 of the 108 MRSA were multidrug resistant with 82.4% being resistant to more than 10 antibiotics. Strains with SCCmec type IV and type 2 ccr, contained SGA and SGL prophage types, were positive for pvl gene and belonged to single PFGE types. This study highlights the important role of biofilm formation and virulence factors of MRSA strains in catheterized patients. PMID:27374894

  8. Spontaneous Staphylococcus xylosus Infection in Mice Deficient in NADPH Oxidase and Comparison with Other Laboratory Mouse Strains

    PubMed Central

    Gozalo, Alfonso S; Hoffmann, Victoria J; Brinster, Lauren R; Elkins, William R; Ding, Li; Holland, Steven M

    2010-01-01

    Staphylococcus xylosus typically is described as a nonpathogenic common inhabitant of rodent skin. Reports of S. xylosus as a primary pathogen in human and veterinary medicine are scarce. Here we report 37 cases, affecting 12 strains of laboratory mice, of spontaneous infections in which S. xylosus was isolated and considered to be the primary pathogen contributing to the death or need for euthanasia of the animal. Infection with S. xylosus was the major cause of death or euthanasia in 3 strains of mice deficient in the production of phagocyte superoxide due to defects in NADPH oxidase. NADPH-oxidase–deficient mice (n = 21) were most susceptible to spontaneous S. xylosus infections. The infections were characterized by abscesses and granulomas in soft tissues, with bacterial migration to internal organs (primarily regional lymph nodes and lungs and, to a lesser degree, muscle, bone, and meninges). In contrast, 9 strains of phagocyte-superoxide–producing mice (n = 16) also had S. xylosus infections, but these were largely confined to eyelids, ocular conjunctiva, and skin and rarely involved other tissues or organs. Because exhaustive bacterial culture and isolation may not be performed routinely from mouse abscesses, S. xylosus infections may be underdiagnosed. S. xylosus should be considered in the differential diagnosis in laboratory mice with abscesses and other skin lesions. This report expands the range of mouse strains and tissues and organs susceptible to spontaneous S. xylosus infection and compares the pathology among various mice strains. PMID:20819397

  9. Finite element modeling for strain rate dependency of fracture resistance in compact bone.

    PubMed

    Charoenphan, S; Polchai, A

    2007-02-01

    Crack growths in compact bones driven by various strain rate levels were studied using finite element modeling. The energy resistance curves in bovine femur cortical bones were characterized, whereas the orthotropic viscoelasticity in bone materials was accounted for to assess the effect of strain rate on the energy resistance curve. The models were also used to justify the anticipated plane strain response as a result of rather thick specimens used in experiments. Similarities were found between the experimental and model results when crack resistance ability exhibited in bones with slow loading rates, while unstable crack growth existed in bones with rapid loading rates. The critical energy release rates slightly decreased with the increase in strain rates. The hybrid experimental and computational method introduced in this study could be beneficial for application in fracture study in which standard experiments cannot be validly performed. PMID:17227094

  10. HDL from apoA1 transgenic mice expressing the 4WF isoform is resistant to oxidative loss of function.

    PubMed

    Berisha, Stela Z; Brubaker, Greg; Kasumov, Takhar; Hung, Kimberly T; DiBello, Patricia M; Huang, Ying; Li, Ling; Willard, Belinda; Pollard, Katherine A; Nagy, Laura E; Hazen, Stanley L; Smith, Jonathan D

    2015-03-01

    HDL functions are impaired by myeloperoxidase (MPO), which selectively targets and oxidizes human apoA1. We previously found that the 4WF isoform of human apoA1, in which the four tryptophan residues are substituted with phenylalanine, is resistant to MPO-mediated loss of function. The purpose of this study was to generate 4WF apoA1 transgenic mice and compare functional properties of the 4WF and wild-type human apoA1 isoforms in vivo. Male mice had significantly higher plasma apoA1 levels than females for both isoforms of human apoA1, attributed to different production rates. With matched plasma apoA1 levels, 4WF transgenics had a trend for slightly less HDL-cholesterol versus human apoA1 transgenics. While 4WF transgenics had 31% less reverse cholesterol transport (RCT) to the plasma compartment, equivalent RCT to the liver and feces was observed. Plasma from both strains had similar ability to accept cholesterol and facilitate ex vivo cholesterol efflux from macrophages. Furthermore, we observed that 4WF transgenic HDL was partially (∼50%) protected from MPO-mediated loss of function while human apoA1 transgenic HDL lost all ABCA1-dependent cholesterol acceptor activity. In conclusion, the structure and function of HDL from 4WF transgenic mice was not different than HDL derived from human apoA1 transgenic mice. PMID:25561462

  11. Salmonella serovars and antimicrobial resistance in strains isolated from wild animals in captivity in Sinaloa, Mexico.

    PubMed

    Silva-Hidalgo, Gabriela; López-Valenzuela, Martin; Juárez-Barranco, Felipe; Montiel-Vázquez, Edith; Valenzuela-Sánchez, Beatriz

    2014-08-01

    The aim of the present study was to evaluate the frequency of antibiotic resistance in Salmonella spp. strains from wild animals in captivity at the Culiacan Zoo and the Mazatlan Aquarium in Sinaloa, Mexico. We identified 17 different Salmonella enterica serovars at a prevalence of 19.90% (Culiacan Zoo) and 6.25% (Mazatlan Aquarium). Antibiotic sensitivity tests revealed that, of the 83 strains studied, 100% were multidrug resistant (MDR). The drugs against which the greatest resistance was observed were: penicillin, erythromycin, dicloxacillin, ampicillin, cephalothin, and chloramphenicol. We therefore conclude that MDR is common among Salmonella isolates originating from wild animals in captivity in Sinaloa. PMID:25282954

  12. TGF-β1 levels and intraocular tissue alterations in mice infected with a virulent type I RH Toxoplasma gondii strain.

    PubMed

    Iqbal, Jamshaid; Al-Awadhi, Mohammad Ahmed; Raghupathy, Raj Gopal

    2016-03-01

    Toxoplasmosis is generally self-limiting in healthy adults but it may cause toxoplasmic retinochoroiditis in cases of congenital infection leading to blindness. The importance of host genetics in determining disease severity in ocular toxoplasmosis has been shown in different inbred mouse strains using low-virulence toxoplasma strain. In this study, we studied intraocular immune response and tissue alterations in the genetically resistant BALB/c and susceptible MF1 mice infected with a virulent type I RH Toxoplasma gondii strain by intravitreal route. We observed a significant up-regulation of IFN-γ and TNF-α to >2200 pg/ml and >300 pg/ml respectively in the blood of both BALB/c and MF1mice during the early stages of post intraocular infection (p < 0.01) but the levels dropped sharply to normal during the late stages of the infection on day 26. The cytokine levels detected were higher in the MF1 mice compared with the BALB/c mice and a relatively higher levels were observed in the aqueous humour (AqH) than in the blood of both group of mice. The TGF-β1 level in the blood and AqH of BALB/c mice remained low throughout the infection period compared with MF1 mice which showed gradual increase to 50 pg/ml in the blood and AqH during the early stages of infection which then further increased 2-fold-132 pg/ml on day 11 (p < 0.01) and remained high till the last day of observation on day 26 except that the TGF-β1 level in AqH dropped sharply to normal level. In summary, our results support that TGF-β1 may down-regulate the effector functions of anti-Toxoplasma cellular immunity during acute toxoplasmosis. We document that a mild Th1 pro-inflammatory response in the BALB/c mice with high IFN-γ and TNF-α and, low TGF-β1 levels during the early stages of infection may have contributed to an effective cellular immune response leading to lower morbidity, mortality and less ocular tissue damage. However in the MF1 mice, a significantly high TGF-β1 level in the blood as

  13. [Prevalence of multidrug-resistant Proteus spp. strains in clinical specimens and their susceptibility to antibiotics].

    PubMed

    Reśliński, Adrian; Gospodarek, Eugenia; Mikucka, Agnieszka

    2005-01-01

    Proteus sp. are opportunistic microorganisms which cause urinary tract and wounds infections, bacteriaemia and sepsis. The aim of this study was analysis of prevalence of multidrug-resistant Proteus sp. strains in clinical specimens and evaluation of their susceptibility to selected antibiotics. The study was carried out of 1499 Proteus sp. strains were isolated in 2000-2003 from patients of departments and dispensaries of the University Hospital CM in Bydgoszcz UMK in Torun. The strains were identified on the basis of appearance of bacterial colonies on bloody and McConkey's agars, movement ability, indole and urease production and in questionable cases biochemical profile in ID GN or ID E (bio-Mérieux) tests was also included. Antibiotic susceptibility was tested by disk diffusion method. Isolated strains were regarded as multidrug-resistant when they were resistant to three kinds of antibiotics at least. Received Proteus sp. the most frequently belonged to P. mirabilis species (92.3%). Most of these bacteria were isolated from urine from patients of Rehabilitation Clinic. All of multidrug-resistant strains were resistant to penicillins and cephalosporins, 98.9% to co-trimoxazole, 77.7% to quinolones, 63.8% to tetracyclines, 38.5% to aminoglycosides, 19.3% to monobactams and 3.4% to carbapenems. Almost 25% multidrug-resistant Proteus sp. produced ESBL. PMID:16134389

  14. Constitutive activation of the Nrf2/Keap1 pathway in insecticide-resistant strains of Drosophila

    PubMed Central

    Misra, Jyoti R.; Lam, Geanette; Thummel, Carl S.

    2013-01-01

    Pesticide resistance poses a major challenge for the control of vector-borne human diseases and agricultural crop protection. Although a number of studies have defined how mutations in specific target proteins can lead to insecticide resistance, much less is known about the mechanisms by which constitutive overexpression of detoxifying enzymes contribute to metabolic pesticide resistance. Here we show that the Nrf2/Keap1 pathway is constitutively active in two laboratory-selected DDT-resistant strains of Drosophila, 91R and RDDTR, leading to the overexpression of multiple detoxifying genes. Disruption of the Drosophila Nrf2 ortholog, CncC, or overexpression of Keap1, is sufficient to block this transcriptional response. In addition, a CncC-responsive reporter is highly active in both DDT-resistant strains and this response is dependent on the presence of an intact CncC binding site in the promoter. Microarray analysis revealed that ~20% of the genes differentially expressed in the 91R strain are known CncC target genes. Finally, we show that CncC is partially active in these strains, consistent with the fitness cost associated with constitutive activation of the pathway. This study demonstrates that the Nrf2/Keap1 pathway contributes to the widespread overexpression of detoxification genes in insecticide-resistant strains and raises the possibility that inhibitors of this pathway could provide effective synergists for insect population control. PMID:24099738

  15. Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice

    PubMed Central

    Lee, Sangmoo; Hwang, Min-Woong; Bae, Joon-Yong; Heo, Jun; Kim, Donghwan; Jang, Seok-Il; Kim, Hyejin; Cheong, Hee Jin; Song, Jin-Won; Song, Ki-Joon; Baek, Luck Ju; Park, Man-Seong

    2014-01-01

    Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection. PMID:24992479

  16. Antibacterial resistance in mice infected with Mycobacterium lepraemurium.

    PubMed Central

    Patel, P J

    1981-01-01

    The differences in susceptibility among C57Bl/6, DBA/2 mice and their F1 hybrids to infections with M. lepraemurium were shown to depend upon the route of infection and size of the inoculum. A method was developed to measure the ability of lymphocytes obtained from M. lepraemurium-infected donors to effect adoptive immunization of syngeneic naive mice against infection with M. tuberculosis. This required sublethal irradiation of recipient mice prior to cell transfer and bacterial challenge. Using this method, it was found that mice infected subcutaneously generated antituberculous immune mechanisms concordantly with the development of delayed-hypersensitivity to antigens of M. lepraemurium. In contrast, intravenously infected mice demonstrated only a transient from of delayed hypersensitivity and little or no antimycobacterial immunity in that progression of infection was associated with a rapid decay of both these functions. Moreover, during the terminal stage, M. lepraemurium-infected mice lost the ability to control the growth of a sublethal intravenous inoculum of the antigenically unrelated bacterium. Listeria monocytogenes. PMID:7039875

  17. [Generation of nalidixic acid-resistant strains and signature-tagged mutants of Actinobacillus pleuropneumoniae].

    PubMed

    Shang, Lin; Li, Wei; Li, Liangjun; Li, Lu; Zhang, Sihua; Li, Tingting; Li, Yaokun; Liu, Lei; Guo, Zhiwei; Zhou, Rui; Chen, Huanchun

    2008-01-01

    Actinobacillus pleuropneumoniae is a very important respiratory pathogen for swine and causes great economic losses in pig industry worldwide. Signature-tagged mutagenesis (STM) is an effective method to identify virulence genes in bacteria. In this study, we selected nalidixic acid-resistant strains of APP serotypes 1 and 3 by in vitro cultivation, and used as receipt strains for constructing transposon mutants by mating with E. coli CC 118 lambdapir or S17-1 lambdapir containing mini-Tn10 tag plasmids pLOF/TAG1-48, with or without the help of E. coli DH5alpha (pRK2073). We screened mutant strains by antibiotics selection, PCR and Southern blot identification. Our data revealed that nalidixic acid-resistance of APP strains could easily be induced in vitro and the resistance was due to the mutation in the DNA gyrase A subunit gene gyrA. In the mating experiments, the bi-parental mating was more effective and easier than tri-parental mating. Different APP strains showed a different mating and transposon efficiency in the bi-parental mating, with the strains of serotype 1 much higher than serotype 3 and the reference strain of serotype 3 higher than the field strains. These data were helpful for the construction of STM mutants and pickup of virulence genes of APP. PMID:18338580

  18. Comparison of two multimetal resistant bacterial strains: Enterobacter sp. YSU and Stenotrophomonas maltophilia ORO2.

    PubMed

    Holmes, Andrew; Vinayak, Anubhav; Benton, Cherise; Esbenshade, Aaron; Heinselman, Carlisle; Frankland, Daniel; Kulkarni, Samatha; Kurtanich, Adrienne; Caguiat, Jonathan

    2009-11-01

    The Y-12 plant in Oak Ridge, TN, which manufactured nuclear weapons during World War II and the Cold War, contaminated East Fork Poplar Creek with heavy metals. The multimetal resistant bacterial strain, Stenotrophomonas maltophilia Oak Ridge strain O2 (S. maltophilia O2), was isolated from East Fork Poplar Creek. Sequence analysis of 16s rDNA suggested that our working strain of S. maltophilia O2 was a strain of Enterobacter. Phylogenetic tree analysis and biochemical tests confirmed that it belonged to an Enterobacter species. This new strain was named Enterobacter sp. YSU. Using a modified R3A growth medium, R3A-Tris, the Hg(II), Cd(II), Zn(II), Cu(II), Au(III), Cr(VI), Ag(I), As(III), and Se(IV) MICs for a confirmed strain of S. maltophilia O2 were 0.24, 0.33, 5, 5, 0.25, 7, 0.03, 14, and 40 mM, respectively, compared to 0.07, 0.24, 0.8, 3, 0.05, 0.4, 0.08, 14, and 40 mM, respectively, for Enterobacter sp. YSU. Although S. maltophilia O2 was generally more metal resistant than Enterobacter sp. YSU, in comparison to Escherichia coli strain HB101, Enterobacter sp. YSU was resistant to Hg(II), Cd(II), Zn(II), Au(III), Ag(I), As(III), and Se(IV). By studying metal resistances in these two strains, it may be possible to understand what makes one microorganism more metal resistant than another microorganism. This work also provided benchmark MICs that can be used to evaluate the metal resistance properties of other bacterial isolates from East Fork Poplar Creek and other metal contaminated sites. PMID:19688378

  19. How Fitness Reduced, Antimicrobial Resistant Bacteria Survive and Spread: A Multiple Pig - Multiple Bacterial Strain Model

    PubMed Central

    Græsbøll, Kaare; Nielsen, Søren Saxmose; Toft, Nils; Christiansen, Lasse Engbo

    2014-01-01

    More than 30% of E. coli strains sampled from pig farms in Denmark over the last five years were resistant to the commonly used antimicrobial tetracycline. This raises a number of questions: How is this high level sustained if resistant bacteria have reduced growth rates? Given that there are multiple susceptible and resistant bacterial strains in the pig intestines, how can we describe their coexistence? To what extent does the composition of these multiple strains in individual pigs influence the total bacterial population of the pig pen? What happens to a complex population when antimicrobials are used? To investigate these questions, we created a model where multiple strains of bacteria coexist in the intestines of pigs sharing a pen, and explored the parameter limits of a stable system; both with and without an antimicrobial treatment. The approach taken is a deterministic bacterial population model with stochastic elements of bacterial distributions and transmission. The rates that govern the model are process-oriented to represent growth, excretion, and uptake from environment, independent of herd and meta-population structures. Furthermore, an entry barrier and elimination process for the individual strains in each pig were implemented. We demonstrate how competitive growth between multiple bacterial strains in individual pigs, and the transmission between pigs in a pen allow for strains of antimicrobial resistant bacteria to persist in a pig population to different extents, and how quickly they can become dominant if antimicrobial treatment is initiated. The level of spread depends in a non-linear way of the parameters that govern excretion and uptake. Furthermore, the sampling of initial distributions of strains and stochastic transmission events give rise to large variation in how homogenous and how resistant the bacterial population becomes. Most important: resistant bacteria are demonstrated to survive with a disadvantage in growth rate of well over 10

  20. Protection from Severe Influenza Virus Infections in Mice Carrying the Mx1 Influenza Virus Resistance Gene Strongly Depends on Genetic Background

    PubMed Central

    Shin, Dai-Lun; Hatesuer, Bastian; Bergmann, Silke; Nedelko, Tatiana

    2015-01-01

    ABSTRACT Influenza virus infections represent a serious threat to human health. Both extrinsic and intrinsic factors determine the severity of influenza. The MX dynamin-like GTPase 1 (Mx1) gene has been shown to confer strong resistance to influenza A virus infections in mice. Most laboratory mouse strains, including C57BL/6J, carry nonsense or deletion mutations in Mx1 and thus a nonfunctional allele, whereas wild-derived mouse strains carry a wild-type Mx1 allele. Congenic C57BL/6J (B6-Mx1r/r) mice expressing a wild-type allele from the A2G mouse strain are highly resistant to influenza A virus infections, to both mono- and polybasic subtypes. Furthermore, in genetic mapping studies, Mx1 was identified as the major locus of resistance to influenza virus infections. Here, we investigated whether the Mx1 protective function is influenced by the genetic background. For this, we generated a congenic mouse strain carrying the A2G wild-type Mx1 resistance allele on a DBA/2J background (D2-Mx1r/r). Most remarkably, congenic D2-Mx1r/r mice expressing a functional Mx1 wild-type allele are still highly susceptible to H1N1 virus. However, pretreatment of D2-Mx1r/r mice with alpha interferon protected them from lethal infections. Our results showed, for the first time, that the presence of an Mx1 wild-type allele from A2G as such does not fully protect mice from lethal influenza A virus infections. These observations are also highly relevant for susceptibility to influenza virus infections in humans. IMPORTANCE Influenza A virus represents a major health threat to humans. Seasonal influenza epidemics cause high economic loss, morbidity, and deaths each year. Genetic factors of the host strongly influence susceptibility and resistance to virus infections. The Mx1 (MX dynamin-like GTPase 1) gene has been described as a major resistance gene in mice and humans. Most inbred laboratory mouse strains are deficient in Mx1, but congenic B6-Mx1r/r mice that carry the wild-type Mx1

  1. Cellular immunity in experimental Echinococcus multilocularis infection. I. Sequential and comparative study of specific in vivo delayed-type hypersensitivity against E. multilocularis antigens in resistant and sensitive mice.

    PubMed Central

    Liance, M; Bresson-Hadni, S; Meyer, J P; Houin, R; Vuitton, D A

    1990-01-01

    Species- or strain-related differences in receptivity of intermediate hosts to E. multilocularis larvae could be related to differences in specific cellular immune response of the host. In order to test this hypothesis, we assessed the delayed-type hypersensitivity (DTH) to E. multilocularis antigens (EmAg) in mice of three strains differing by their sensitivity (AKR and C57BL.6) or resistance (C57BL.10) to E. multilocularis infection. DTH was determined by measuring in vivo the foot-pad response 24 h after an EmAg antigenic challenge. The level of positive response was evaluated in immunized mice; however, a typical DTH response was only observed by immunizing mice with a strong adjuvant schedule. Course of DTH in the immunized mice was shown to be somewhat different in sensitive and resistant mice. The differences were much more marked in mice infected with proliferative E. multilocularis larvae. The levels of the footpad response was significantly higher in resistant mice, although the peak of the reaction was obtained later than in sensitive mice. DTH, expressed by the foot-pad response against EmAg, remained significant for the entire period of observation in sensitive as well as in resistant mice. There was no correlation between receptivity of the murine hosts and levels of specific antibodies against EmAg. These results suggest a relationship between resistance to E. multilocularis infection and intensity and/or course of DTH in mice. The resistance could be mediated by some particularities of the in situ cellular immune response in the periparasitic granuloma. PMID:2242618

  2. Genotyping and drug resistance patterns of M. tuberculosis strains in Pakistan

    PubMed Central

    Tanveer, Mahnaz; Hasan, Zahra; Siddiqui, Amna R; Ali, Asho; Kanji, Akbar; Ghebremicheal, Solomon; Hasan, Rumina

    2008-01-01

    Background The incidence of tuberculosis in Pakistan is 181/100,000 population. However, information about transmission and geographical prevalence of Mycobacterium tuberculosis strains and their evolutionary genetics as well as drug resistance remains limited. Our objective was to determine the clonal composition, evolutionary genetics and drug resistance of M. tuberculosis isolates from different regions of the country. Methods M. tuberculosis strains isolated (2003–2005) from specimens submitted to the laboratory through collection units nationwide were included. Drug susceptibility was performed and strains were spoligotyped. Results Of 926 M. tuberculosis strains studied, 721(78%) were grouped into 59 "shared types", while 205 (22%) were identified as "Orphan" spoligotypes. Amongst the predominant genotypes 61% were Central Asian strains (CAS ; including CAS1, CAS sub-families and Orphan Pak clusters), 4% East African-Indian (EAI), 3% Beijing, 2% poorly defined TB strains (T), 2% Haarlem and LAM (0.2). Also TbD1 analysis (M. tuberculosis specific deletion 1) confirmed that CAS1 was of "modern" origin while EAI isolates belonged to "ancestral" strain types. Prevalence of CAS1 clade was significantly higher in Punjab (P < 0.01, Pearsons Chi-square test) as compared with Sindh, North West Frontier Province and Balochistan provinces. Forty six percent of isolates were sensitive to five first line antibiotics tested, 45% were Rifampicin resistant, 50% isoniazid resistant. MDR was significantly associated with Beijing strains (P = 0.01, Pearsons Chi-square test) and EAI (P = 0.001, Pearsons Chi-square test), but not with CAS family. Conclusion Our results show variation of prevalent M. tuberculosis strain with greater association of CAS1 with the Punjab province. The fact that the prevalent CAS genotype was not associated with drug resistance is encouraging. It further suggests a more effective treatment and control programme should be successful in reducing the

  3. Investigation of Metallo Beta Lactamases and Oxacilinases in Carbapenem Resistant Acinetobacter baumannii Strains Isolated from Inpatients

    PubMed Central

    Aksoy, M. Duygu; Çavuşlu, Şaban; Tuğrul, H. Murat

    2015-01-01

    Background: Resistance to beta-lactam antibiotics is widespread among Acinetobacter strains. Plasmid-mediated metallo beta lactamases (MBL) are responsible for carbapenem resistance, as are oxacillinases (OXA). In recent years, MBL producing carbapenem-resistant strains have been reported in the world and in Turkey in increasing rates. In our country, besides the OXA 51-like enzyme which is inherent in A. baumannii strains, OXA 58-like and OXA 23-like carbapenemases producing strains have also been widely detected. In addition, Verona Imipenemase (VIM) and (IMP)-type MBL have been reported in some centers. Aims: The aim of our study was to investigate the presence of carbapenemases in Acinetobacter strains isolated from hospitalized patients in Edirne. Study Design: Cross-sectional study. Methods: A total of 52 imipenem-resistant A. baumannii strains isolated between January and March 2013 were investigated. The presence of MBL was described phenotypically by the combined disk diffusion test (CDDT), double disk synergy test (DDST), MBL E-test (only performed in 28 strains) and modified Hodge test. blaIMP, blaVIM, blaGIM, blaSIM, blaSPM genes and blaOXA-23, blaOXA-51, blaOXA-40, blaOXA-58 genes were investigated by multiplex polymerase chain reaction (PCR). The blaNDM-1 gene was determined by PCR. Results: By modified Hodge test, 50 strains (96%) were found to be MBL positive. Positivity of MBL was 21% by both CDDT (0.1 M EDTA) and DDST. Twenty-four of 28 strains (85.7%) were positive by MBL E-test. OXA 23-like and OXA 51-like carbapenemases were detected in all strains, but OXA 58-like and OXA 40-like carbapenemases-producing A. baumannii were not detected. Also, MBL genes were not detected by genotypic methods. Conclusion: Only OXA 23-like carbapenemase was responsible for carbapenem resistance in carbapenem-resistant Acinetobacter strains in Edirne. The MBL-producing Acinetobacter strain is not yet a problem in our hospital. MBL resistance was found by

  4. Flexible and mechanical strain resistant large area SERS active substrates

    NASA Astrophysics Data System (ADS)

    Singh, J. P.; Chu, Hsiaoyun; Abell, Justin; Tripp, Ralph A.; Zhao, Yiping

    2012-05-01

    We report a cost effective and facile way to synthesize flexible, uniform, and large area surface enhanced Raman scattering (SERS) substrates using an oblique angle deposition (OAD) technique. The flexible SERS substrates consist of 1 μm long, tilted silver nanocolumnar films deposited on flexible polydimethylsiloxane (PDMS) and polyethylene terephthalate (PET) sheets using OAD. The SERS enhancement activity of these flexible substrates was determined using 10-5 M trans-1,2-bis(4-pyridyl) ethylene (BPE) Raman probe molecules. The in situ SERS measurements on these flexible substrates under mechanical (tensile/bending) strain conditions were performed. Our results show that flexible SERS substrates can withstand a tensile strain (ε) value as high as 30% without losing SERS performance, whereas the similar bending strain decreases the SERS performance by about 13%. A cyclic tensile loading test on flexible PDMS SERS substrates at a pre-specified tensile strain (ε) value of 10% shows that the SERS intensity remains almost constant for more than 100 cycles. These disposable and flexible SERS substrates can be integrated with biological substances and offer a novel and practical method to facilitate biosensing applications.

  5. Colistin-Resistant Acinetobacter baumannii Clinical Strains with Deficient Biofilm Formation

    PubMed Central

    Dafopoulou, Konstantina; Xavier, Basil Britto; Hotterbeekx, An; Janssens, Lore; Lammens, Christine; Dé, Emmanuelle; Goossens, Herman; Tsakris, Athanasios; Malhotra-Kumar, Surbhi

    2015-01-01

    In two pairs of clinical colistin-susceptible/colistin-resistant (Csts/Cstr) Acinetobacter baumannii strains, the Cstr strains showed significantly decreased biofilm formation in static and dynamic assays (P < 0.001) and lower relative fitness (P < 0.05) compared with those of the Csts counterparts. The whole-genome sequencing comparison of strain pairs identified a mutation converting a stop codon to lysine (*241K) in LpsB (involved in lipopolysaccharide [LPS] synthesis) in one Cstr strain and a frameshift mutation in CarO and the loss of a 47,969-bp element containing multiple genes associated with biofilm production in the other. PMID:26666921

  6. Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.

    PubMed

    Mitchell, Sarah J; Madrigal-Matute, Julio; Scheibye-Knudsen, Morten; Fang, Evandro; Aon, Miguel; González-Reyes, José A; Cortassa, Sonia; Kaushik, Susmita; Gonzalez-Freire, Marta; Patel, Bindi; Wahl, Devin; Ali, Ahmed; Calvo-Rubio, Miguel; Burón, María I; Guiterrez, Vincent; Ward, Theresa M; Palacios, Hector H; Cai, Huan; Frederick, David W; Hine, Christopher; Broeskamp, Filomena; Habering, Lukas; Dawson, John; Beasley, T Mark; Wan, Junxiang; Ikeno, Yuji; Hubbard, Gene; Becker, Kevin G; Zhang, Yongqing; Bohr, Vilhelm A; Longo, Dan L; Navas, Placido; Ferrucci, Luigi; Sinclair, David A; Cohen, Pinchas; Egan, Josephine M; Mitchell, James R; Baur, Joseph A; Allison, David B; Anson, R Michael; Villalba, José M; Madeo, Frank; Cuervo, Ana Maria; Pearson, Kevin J; Ingram, Donald K; Bernier, Michel; de Cabo, Rafael

    2016-06-14

    Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions. PMID:27304509

  7. Abamectin resistance in strains of vegetable leafminer, Liriomyza sativae (Diptera: Agromyzidae) is linked to elevated glutathione S-transferase activity.

    PubMed

    Wei, Qing-Bo; Lei, Zhong-Ren; Nauen, Ralf; Cai, Du-Cheng; Gao, Yu-Lin

    2015-04-01

    Abamectin resistance was selected in the vegetable leafminer, Liriomyza sativae (Blanchard) (Diptera: Agromyzidae) under laboratory conditions, and cross-resistance patterns and possible resistance mechanisms in the abamectin-resistant strains (AL-R, AF-R) were investigated. Compared with the susceptible strain (SS), strain AL-R displayed 39-fold resistance to abamectin after 20 selection cycles during 25 generations, and strain AF-R exhibited 59-fold resistance to abamectin after 16 selection cycles during 22 generations. No cross-resistance to cyromazine was found in both abamectin-resistant strains. However, we failed to select for cyromazine resistance in L. sativae under laboratory conditions by conducting 17 selection cycles during 22 generations. However, moderate levels of cross-resistance to abamectin (6-9 fold) were observed in strains which received cyromazine treatments. Biochemical analysis showed that glutathione S-transferase (GST) activity in both abamectin-resistant strains (AL-R, AF-R) was significantly higher than in the susceptible strain (SS), suggesting metabolically driven resistance to abamectinin L. sativae. Recommendations of mixtures or rotation of cyromazine and abamectin should be considered carefully, as consecutive cyromazine treatments may select for low-level cross-resistance to abamectin. PMID:25813391

  8. Phenotypic and Genotypic Alterations of Durancin GL-Resistant Enterococcus durans Strains.

    PubMed

    Du, Lihui; Liu, Lingping; Liu, Fang; Ju, Xingrong; Yuan, Jian

    2016-06-01

    The emergence and spread of bacteriocin-resistant bacteria threaten the efficiency of bacteriocin usage as food preservatives. In this experiment, 19 selected Enterococcus durans strains acquired resistance after exposure to durancin GL, and the mutants had similar intermediate levels of resistance. One wild-type E. durans KLDS 6.0603 and its two resistant mutants, E. durans KLDS 6.0603-2 and E. durans KLDS 6.0603-3, were used to characterize phenotypic and genotypic differences. Approximately 100 μg/mL of durancin GL can penetrate the cytoplasmic membrane of E. durans KLDS 6.0603, causing damage to bacterial cells, but cannot penetrate E. durans KLDS 6.0603-2 and KLDS 6.0603-3 membranes. Unsaturated fatty acid content in resistant strains was significantly increased compared with wild-type strains, indicating that the former has more fluidity of cell membrane than the latter. Decreased mannose phosphotransferase system gene expression (mptD) was observed in the two resistant strains. Results showed that the factors, including the increased unsaturated fatty acid and decreased mptD expression, could contribute to durancin GL resistance. PMID:27096434

  9. The impact of strain diversity and mixed infections on the evolution of resistance to Bacillus thuringiensis

    PubMed Central

    Raymond, Ben; Wright, Denis J.; Crickmore, Neil; Bonsall, Michael B.

    2013-01-01

    Pesticide mixtures can reduce the rate at which insects evolve pesticide resistance. However, with live biopesticides such as the naturally abundant pathogen Bacillus thuringiensis (Bt), a range of additional biological considerations might affect the evolution of resistance. These can include ecological interactions in mixed infections, the different rates of transmission post-application and the impact of the native biodiversity on the frequency of mixed infections. Using multi-generation selection experiments, we tested how applications of single and mixed strains of Bt from diverse sources (natural isolates and biopesticides) affected the evolution of resistance in the diamondback moth, Plutella xylostella, to a focal strain. There was no significant difference in the rate of evolution of resistance between single and mixed-strain applications although the latter did result in lower insect populations. The relative survivorship of Bt-resistant genotypes was higher in the mixed-strain treatment, in part owing to elevated mortality of susceptible larvae in mixtures. Resistance evolved more quickly with treatments that contained natural isolates, and biological differences in transmission rate may have contributed to this. Our data indicate that the use of mixtures can have unexpected consequences on the fitness of resistant and susceptible insects. PMID:24004937

  10. Resistivity and strain behavior during transformation cycling in nickel-titanium

    SciTech Connect

    Lee, K.H.

    1983-09-01

    The effects of stress and transformation fatigue cycling on the resistivity and strain behaviors in Ni-Ti wires were studied. The samples consisted of uncycled wires and wires cycled 5.78 million times in shape memory heat engine devices. Measurements of resistivity and strain were made as a function of temperature at various applied uniaxial tensile stresses. The resistivity-temperature and strain-temperature behaviors were observed to depend on the temperature or the portion of the transformation cycle at which the stress change is made. It was found that the low temperature resistivity and strain increased with increasing stress. Also, the transformation fatigue cycled wires showed a higher and broader resistivity peak with two-stage behavior. The increase in strain with increasing stress is explained in terms of the crystallographic multiplicity of martensite plates and the alteration of the martensite plate structure in response to the applied stress. Prior transformation fatigue cycling causes a decrease in the applied stress dependence of the total strain changes. Also, the shape of curve is changed upon annealing and the M/sub S/ temperature is lowered by transformation fatigue cycling. The lower M/sub S/ temperature upon cycling is due to a stabilization of the high-temperature phase due to transformation-induced dislocations acting as an impediment to further martensite nucleation. Another effect of the stress is to increase the resistivity of the low-temperature phase. However, it was noticed that the stress should be increased above M/sub S/ temperature to increase the resistivity of the low temperature phase. The increase in low-temperature resistivity is partially due to the change in form factor during transformation shape change and due to the alteration of the martensite variants in a preferred direction.

  11. Behavioral Avoidance - Will Physiological Insecticide Resistance Level of Insect Strains Affect Their Oviposition and Movement Responses?

    PubMed Central

    Nansen, Christian; Baissac, Olivier; Nansen, Maria; Powis, Kevin; Baker, Greg

    2016-01-01

    Agricultural organisms, such as insect herbivores, provide unique opportunities for studies of adaptive evolutionary processes, including effects of insecticides on movement and oviposition behavior. In this study, Brassica leaves were treated with one of two non-systemic insecticides and exposed to two individual strains (referred to as single or double resistance) of diamondback moth (Plutella xylostella) (DBM) exhibiting physiological resistance. Behavioral responses by these two strains were compared as part of characterizing the relative effect of levels of physiological resistance on the likelihood of insects showing signs of behavioral avoidance. For each DBM strain, we used choice bioassays to quantify two possible types of behavioral avoidance: 1) females ovipositing predominantly on leaf surfaces without insecticides, and 2) larvae avoiding insecticide-treated leaf surfaces. In three-choice bioassays (leaves with no pesticide, 50% coverage with pesticide, or 100% coverage with pesticide), females from the single resistance DBM strain laid significantly more eggs on water treated leaves compared to leaves with 100% insecticide coverage (both gamma-cyhalothrin and spinetoram). Females from the double resistance DBM strain also laid significantly more eggs on water treated leaves compared to leaves with 100% gamma-cyhalothrin, while moths did not adjust their oviposition behavior in response to spinetoram. Larvae from the single resistance DBM strain showed a significant increase in mobility in response to both insecticides and avoided insecticide-treated portions of leaves when given a choice. On the other hand, DBM larvae from the double resistance strain showed a significant decrease in mobility in response to insecticides, and they did not avoid insecticide-treated portions of leaves when given a choice. Our results suggest that pest populations with physiological resistance may show behavioral avoidance, as resistant females avoided oviposition on

  12. Human IL-32 expression protects mice against a hypervirulent strain of Mycobacterium tuberculosis

    PubMed Central

    Bai, Xiyuan; Shang, Shaobin; Henao-Tamayo, Marcela; Basaraba, Randall J.; Ovrutsky, Alida R.; Matsuda, Jennifer L.; Takeda, Katsuyuki; Chan, Mallory M.; Dakhama, Azzeddine; Kinney, William H.; Trostel, Jessica; Bai, An; Honda, Jennifer R.; Achcar, Rosane; Hartney, John; Joosten, Leo A. B.; Kim, Soo-Hyun; Orme, Ian; Dinarello, Charles A.; Ordway, Diane J.; Chan, Edward D.

    2015-01-01

    Silencing of interleukin-32 (IL-32) in a differentiated human promonocytic cell line impairs killing of Mycobacterium tuberculosis (MTB) but the role of IL-32 in vivo against MTB remains unknown. To study the effects of IL-32 in vivo, a transgenic mouse was generated in which the human IL-32γ gene is expressed using the surfactant protein C promoter (SPC-IL-32γTg). Wild-type and SPC-IL-32γTg mice were infected with a low-dose aerosol of a hypervirulent strain of MTB (W-Beijing HN878). At 30 and 60 d after infection, the transgenic mice had 66% and 85% fewer MTB in the lungs and 49% and 68% fewer MTB in the spleens, respectively; the transgenic mice also exhibited greater survival. Increased numbers of host-protective innate and adaptive immune cells were present in SPC-IL-32γTg mice, including tumor necrosis factor-alpha (TNFα) positive lung macrophages and dendritic cells, and IFN-gamma (IFNγ) and TNFα positive CD4+ and CD8+ T cells in the lungs and mediastinal lymph nodes. Alveolar macrophages from transgenic mice infected with MTB ex vivo had reduced bacterial burden and increased colocalization of green fluorescent protein-labeled MTB with lysosomes. Furthermore, mouse macrophages made to express IL-32γ but not the splice variant IL-32β were better able to limit MTB growth than macrophages capable of producing both. The lungs of patients with tuberculosis showed increased IL-32 expression, particularly in macrophages of granulomas and airway epithelial cells but also B cells and T cells. We conclude that IL-32γ enhances host immunity to MTB. PMID:25820174

  13. Neither Dectin-2 nor the Mannose Receptor Is Required for Resistance to Coccidioides immitis in Mice

    PubMed Central

    Viriyakosol, Suganya; Jimenez, Maria del Pilar; Saijo, Sinobu

    2014-01-01

    We investigated the roles of the mannose receptor (MR) and Dectin-2 in resistance to pulmonary coccidioidomycosis in C57BL/6 (B6) mice and in the interaction of myeloid cells with spherules, using B6 mice with targeted mutations in Mrc1 and Clec4n. Spherules are the tissue form of Coccidioides, and we determined that the MR on bone marrow-derived dendritic cells (BMDC) was important for recognition of spherules (formalin-killed spherules [FKS]) and for secretion of interleukin 10 (IL-10) and proinflammatory cytokines in response to FKS by both elicited macrophages and BMDC. Infected MR knockout (KO) mice produced more IL-10 in their lungs than did B6 mice, and MR KO mice also made more protective Th-17 cytokines. In contrast to the MR, Dectin-2 was not required for recognition of FKS by BMDC or for the production of cytokines by BMDC in response to FKS. However, Dectin-2 KO was required for stimulation of elicited peritoneal macrophages. Despite that, lung cytokine levels were not significantly different in Dectin-2 KO mice and B6 mice 14 days after infection, except for IL-1β, which was higher in Dectin-2 KO lungs. Although both Dectin-2−/− and MR−/− myeloid cells had reduced proinflammatory cytokine responses to FKS in vitro, neither MR nor Dectin-2 deficiency reduced the resistance of B6 mice to pulmonary coccidioidomycosis. PMID:24379281

  14. Neither dectin-2 nor the mannose receptor is required for resistance to Coccidioides immitis in mice.

    PubMed

    Viriyakosol, Suganya; Jimenez, Maria Del Pilar; Saijo, Sinobu; Fierer, Joshua

    2014-03-01

    We investigated the roles of the mannose receptor (MR) and Dectin-2 in resistance to pulmonary coccidioidomycosis in C57BL/6 (B6) mice and in the interaction of myeloid cells with spherules, using B6 mice with targeted mutations in Mrc1 and Clec4n. Spherules are the tissue form of Coccidioides, and we determined that the MR on bone marrow-derived dendritic cells (BMDC) was important for recognition of spherules (formalin-killed spherules [FKS]) and for secretion of interleukin 10 (IL-10) and proinflammatory cytokines in response to FKS by both elicited macrophages and BMDC. Infected MR knockout (KO) mice produced more IL-10 in their lungs than did B6 mice, and MR KO mice also made more protective Th-17 cytokines. In contrast to the MR, Dectin-2 was not required for recognition of FKS by BMDC or for the production of cytokines by BMDC in response to FKS. However, Dectin-2 KO was required for stimulation of elicited peritoneal macrophages. Despite that, lung cytokine levels were not significantly different in Dectin-2 KO mice and B6 mice 14 days after infection, except for IL-1β, which was higher in Dectin-2 KO lungs. Although both Dectin-2(-/-) and MR(-/-) myeloid cells had reduced proinflammatory cytokine responses to FKS in vitro, neither MR nor Dectin-2 deficiency reduced the resistance of B6 mice to pulmonary coccidioidomycosis. PMID:24379281

  15. Genomic Stability over 9 Years of an Isoniazid Resistant Mycobacterium tuberculosis Outbreak Strain in Sweden

    PubMed Central

    Sandegren, Linus; Groenheit, Ramona; Koivula, Tuija; Ghebremichael, Solomon; Advani, Abdolreza; Castro, Elsie; Pennhag, Alexandra; Hoffner, Sven; Mazurek, Jolanta; Pawlowski, Andrzej; Kan, Boris; Bruchfeld, Judith; Melefors, Öjar; Källenius, Gunilla

    2011-01-01

    In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e.g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance. PMID:21304944

  16. Analysis of plasmids in nosocomial strains of multiple-antibiotic-resistant Staphylococcus aureus.

    PubMed Central

    Lyon, B R; May, J W; Skurray, R A

    1983-01-01

    Nosocomial infections caused by Staphylococcus aureus strains resistant to methicillin and multiple antibiotics have reached epidemic proportions in Melbourne, Australia, over the past 5 years. Plasmid analysis of representative clinical isolates demonstrated the presence of three classes of plasmid DNA in most strains. Resistance to gentamicin, kanamycin, and tobramycin was usually mediated by an 18-megadalton plasmid but could also be encoded by a related 22-megadalton plasmid. Two distinguishable plasmids of 3 megadaltons each endowed resistance to chloramphenicol, and the third class consisted of small plasmids, each approximately 1 megadalton in size, with no attributable function. An extensive array of resistance determinants, including some which have usually been associated with a plasmid locus, were found to exist on the chromosome. Evidence that resistance to gentamicin, kanamycin, and tobramycin is chromosomally encoded in some clinical isolates suggests that this determinant may have undergone genetic translocation onto the staphylococcal chromosome. Images PMID:6311086

  17. Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis

    PubMed Central

    Ishii, Kenichi; Tabuchi, Fumiaki; Matsuo, Miki; Tatsuno, Keita; Sato, Tomoaki; Okazaki, Mitsuhiro; Hamamoto, Hiroshi; Matsumoto, Yasuhiko; Kaito, Chikara; Aoyagi, Tetsuji; Hiramatsu, Keiichi; Kaku, Mitsuo; Moriya, Kyoji; Sekimizu, Kazuhisa

    2015-01-01

    The development of vancomycin (VCM) resistance in Staphylococcus aureus threatens global health. Studies of the VCM-resistance mechanism and alternative therapeutic strategies are urgently needed. We mutagenized S. aureus laboratory strains and methicillin-resistant S. aureus (MRSA) with ethyl methanesulfonate, and isolated mutants that exhibited high resistance to VCM (minimum inhibitory concentration = 32 μg/ml). These VCM-resistant strains were sensitive to linezolid and rifampicin, and partly to arbekacin and daptomycin. Beta-lactams had synergistic effects with VCM against these mutants. VCM-resistant strains exhibited a 2-fold increase in the cell wall thickness. Several genes were commonly mutated among the highly VCM-resistant mutants. These findings suggest that MRSA has a potential to develop high VCM resistance with cell wall thickening by the accumulation of mutations. PMID:26603341

  18. High prevalence of methicillin resistant staphylococci strains isolated from surgical site infections in Kinshasa

    PubMed Central

    Iyamba, Jean-Marie Liesse; Wambale, José Mulwahali; Lukukula, Cyprien Mbundu; Takaisi-Kikuni, Ntondo za Balega

    2014-01-01

    Introduction Surgical site infections (SSIs) after surgery are usually caused by Staphylococcus aureus and coagulase-negative staphylococci (CNS). In low income countries, methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase-negative staphylococci (MR-CNS) surgical site infections are particularly associated with high treatment cost and remain a source of mortality and morbidity. This study aimed to determine the prevalence and the sensitivity to antibiotics of MRSA and MR-CNS isolated from SSIs. Methods Wound swabs were collected from 130 hospitalized surgical patients in two major hospitals of Kinshasa. S. aureus and CNS strains were identified by standard microbiological methods and latex agglutination test (Pastorex Staph-Plus). The antibiotic susceptibility of all staphylococcal strains was carried out using disk-diffusion method. Results Eighty nine staphylococcal strains were isolated. Out of 74 S. aureus and 15 CNS isolated, 47 (63.5%) and 9 (60%) were identified as MRSA and MR-CNS respectively. Among the MRSA strains, 47 strains (100%) were sensitive to imipenem, 39 strains (89%) to amoxycillin-clavulanic acid and 38 strains (81%) to vancomycin. All MR-CNS were sensitive to imipenem, amoxycillin-clavulanic acid and vancomycin. The isolated MRSA and MR-CNS strains showed multidrug resistance. They were both resistant to ampicillin, cotrimoxazole, erythromycin, clindamycin, ciprofloxacin, cefotaxime and ceftazidime. Conclusion The results of the present study showed a high prevalence of MRSA and MR-CNS. Imipenem, amoxycillin-clavulanic acid and vancomycin were the most active antibiotics. This study suggests that antibiotic surveillance policy should become national priority as MRSA and MR-CNS were found to be multidrug resistant. PMID:25478043

  19. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    PubMed

    Bennett, Brian J; Davis, Richard C; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C; Hazen, Stanley L; Gargalovic, Peter S; Lusis, Aldons J

    2015-12-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

  20. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains

    PubMed Central

    Bennett, Brian J.; Davis, Richard C.; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R. Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C.; Hazen, Stanley L.; Gargalovic, Peter S.; Lusis, Aldons J.

    2015-01-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

  1. Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice

    PubMed Central

    Zhou, Linkang; Park, Shi-Young; Xu, Li; Xia, Xiayu; Ye, Jing; Su, Lu; Jeong, Kyeong-Hoon; Hur, Jang Ho; Oh, Hyunhee; Tamori, Yoshikazu; Zingaretti, Cristina M.; Cinti, Saverio; Argente, Jesús; Yu, Miao; Wu, Lizhen; Ju, Shenghong; Guan, Feifei; Yang, Hongyuan; Choi, Cheol Soo; Savage, David B.; Li, Peng

    2015-01-01

    Fsp27 is a lipid droplet-associated protein almost exclusively expressed in adipocytes where it facilitates unilocular lipid droplet formation. In mice, Fsp27 deficiency is associated with increased basal lipolysis, ‘browning’ of white fat and a healthy metabolic profile, whereas a patient with congenital CIDEC deficiency manifested an adverse lipodystrophic phenotype. Here we reconcile these data by showing that exposing Fsp27-null mice to a substantial energetic stress by crossing them with ob/ob mice or BATless mice, or feeding them a high-fat diet, results in hepatic steatosis and insulin resistance. We also observe a striking reduction in adipose inflammation and increase in adiponectin levels in all three models. This appears to reflect reduced activation of the inflammasome and less adipocyte death. These findings highlight the importance of Fsp27 in facilitating optimal energy storage in adipocytes and represent a rare example where adipose inflammation and hepatic insulin resistance are disassociated. PMID:25565658

  2. Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice.

    PubMed

    Zhou, Linkang; Park, Shi-Young; Xu, Li; Xia, Xiayu; Ye, Jing; Su, Lu; Jeong, Kyeong-Hoon; Hur, Jang Ho; Oh, Hyunhee; Tamori, Yoshikazu; Zingaretti, Cristina M; Cinti, Saverio; Argente, Jesús; Yu, Miao; Wu, Lizhen; Ju, Shenghong; Guan, Feifei; Yang, Hongyuan; Choi, Cheol Soo; Savage, David B; Li, Peng

    2015-01-01

    Fsp27 is a lipid droplet-associated protein almost exclusively expressed in adipocytes where it facilitates unilocular lipid droplet formation. In mice, Fsp27 deficiency is associated with increased basal lipolysis, 'browning' of white fat and a healthy metabolic profile, whereas a patient with congenital CIDEC deficiency manifested an adverse lipodystrophic phenotype. Here we reconcile these data by showing that exposing Fsp27-null mice to a substantial energetic stress by crossing them with ob/ob mice or BATless mice, or feeding them a high-fat diet, results in hepatic steatosis and insulin resistance. We also observe a striking reduction in adipose inflammation and increase in adiponectin levels in all three models. This appears to reflect reduced activation of the inflammasome and less adipocyte death. These findings highlight the importance of Fsp27 in facilitating optimal energy storage in adipocytes and represent a rare example where adipose inflammation and hepatic insulin resistance are disassociated. PMID:25565658

  3. Different attentional abilities among inbred mice strains using virtual object recognition task (VORT): SNAP25⁺/⁻ mice as a model of attentional deficit.

    PubMed

    Braida, Daniela; Ponzoni, Luisa; Matteoli, Michela; Sala M, Mariaelvina

    2016-01-01

    Autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), schizophrenia, Alzheimer's and Parkinson's disease are characterized by attentional deficits. In the present study we first applied the virtual object recognition test (VORT), where 3D objects were replaced with highly discriminated geometrical shapes and presented on two 3.5-inch widescreen displays, in different inbred mice strains (C57BL/6N, DBA/2J, BALB/cJ), in comparison with the standard object recognition test (NOR). In both NOR and VORT, there was a progressive decay of performance in terms of reduced discrimination index from 5 min to 72 h of inter-trial delay in all strains. However, BALB/cJ inbred mice showed a better long lasting performance than C57BL/6N and DBA/2J, when tested in NOR. In VORT, BALB/cJ showed the best performance. Total exploration time was always higher in BALB/cJ than C57BL/6N and DBA/2J mice. C57BL/6N were less explorative strain than DBA/2J and BALB/cJ mice. When VORT was applied to SNAP-25(+/-) mice, an impairment in both NOR and VORT was shown. However, when moving shapes were applied, these heterozygous mice improved their performance, suggesting that the introduction of motion is a strong cue that makes the task more valuable to study attention deficits. Taken together, these data indicate that VORT provides a useful and rapid tool to identify the attentional deficit in different inbred strains and genetically modified mice, enhancing the value of psychiatric mouse models. PMID:26300453

  4. Isolation, identification and antibiotic resistance of Campylobacter strains isolated from domestic and free-living pigeons.

    PubMed

    Dudzic, A; Urban-Chmiel, R; Stępień-Pyśniak, D; Dec, M; Puchalski, A; Wernicki, A

    2016-04-01

    1. The aim of this study was to evaluate the occurrence of Campylobacter spp. in domestic and free-living pigeons and to evaluate the antibiotic resistance profiles. 2. The material consisted of cloacal swabs obtained from 108 homing pigeons and fresh faeces from 72 wild birds from Lublin and its vicinity. The identification of strains isolated on differential/selective media for Campylobacter spp. was carried out by MALDI-TOF and PCR. The susceptibility to antibiotics was evaluated by minimum inhibitory concentration (MIC) in Mueller-Hinton broth. 3. A total of 35 strains of Campylobacter spp. were isolated; 27 were identified as Campylobacter jejuni and 8 as Campylobacter coli. Over half of the isolates were resistant to erythromycin and streptomycin, 40% of strains were resistant to tetracycline and ampicillin and 37% isolates were resistant to amoxicillin. Resistance to two or more antibiotics was observed in all strains tested. 4. The results indicate that both domestic and free-living pigeons are reservoirs for bacteria of the genus Campylobacter, which are characterised by varied and growing resistance to commonly used antibiotics. PMID:26841300

  5. The isolation of a field strain of Haemonchus contortus in Queensland showing multiple anthelmintic resistance.

    PubMed

    Green, P E; Forsyth, B A; Rowan, K J; Payne, G

    1981-02-01

    Following the apparent failure of levamisole to control infections of Haemonchus contortus in sheep at Lawes in south eastern Queensland, a strain of this parasite was isolated at the Animal Research Institute, Yeerongpilly. This strain was used to infect sheep at Yeerongpilly and the Merrindale Research Station, Victoria where four experiments to classify the resistance pattern of the parasite were carried out. Resistance to thiabendazole was first suspected in 1969, and these experiments confirmed that resistance to this drug was still present. They also showed that a strong degree of resistance had been developed to both levamisole and morantel tartrate. Other benzimidazole anthelmintics and also the organophosphorus compound naphthalophos were only moderately effective against the original isolate but rafoxanide, nitroxynil and phenothiazine were almost 100% effective. Other highly effective chemicals were disophenol and closantel. After passaging the strain for four generations with both levamisole and albendazole, resistance to both naphthalophos and the newer benzimidazole anthelmintics increased dramatically. This is the first report of a field strain of H. contortus exhibiting resistance to benzimidazole, non-benzimidazole and organophosphorus anthelmintics. PMID:7259650

  6. First report of an OXA-48-producing multidrug-resistant Proteus mirabilis strain from Gaza, Palestine.

    PubMed

    Chen, Liang; Al Laham, Nahed; Chavda, Kalyan D; Mediavilla, Jose R; Jacobs, Michael R; Bonomo, Robert A; Kreiswirth, Barry N

    2015-07-01

    We report the first multidrug-resistant Proteus mirabilis strain producing the carbapenemase OXA-48 (Pm-OXA-48) isolated at Al-Shifa hospital in Gaza, Palestine. Draft genome sequencing of Pm-OXA-48 identified 16 antimicrobial resistance genes, encoding resistance to β-lactams, aminoglycosides, fluoroquinolones, phenicols, streptothricin, tetracycline, and trimethoprim-sulfamethoxazole. Complete sequencing of the bla(OXA-48)-harboring plasmid revealed that it is a 72 kb long IncL/M plasmid, harboring carbapenemase gene bla(OXA-48), extended spectrum β-lactamase gene bla(CTX-M-14), and aminoglycoside resistance genes strA, strB, and aph(3')-VIb. PMID:25896692

  7. The Resistance and Strength of Soft Solder Splices between Conductors in MICE Coils

    SciTech Connect

    Wu, Hong; Pan, Heng; Green, Michael A; Dietderich, Dan; Gartner, T. E.; Higley, Hugh C; Mentink, M.; Xu, FengYu; Trillaud, F.; Liu, X. K.; Wang, Li; Zheng, S. X.; Tam, D.G.

    2010-08-03

    Two of the three types of MICE magnets will have splices within their coils. The MICE coupling coils may have as many as fifteen one-meter long splices within them. Each of the MICE focusing coils may have a couple of 0.25-meter long conductor splices. Equations for the calculation of resistance of soldered lap splices of various types are presented. This paper presents resistance measurements of soldered lap splices of various lengths. Measured splice resistance is shown for one-meter long splices as a function of the fabrication method. Another important consideration is the strength of the splices. The measured breaking stress of splices of various lengths is presented in this paper. Tin-lead solders and tin-silver solders were used for the splices that were tested. From the data given in this report, the authors recommend that the use of lead free solders be avoided for low temperature coils.

  8. Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice

    PubMed Central

    Caricilli, Andréa M.; Picardi, Paty K.; de Abreu, Lélia L.; Ueno, Mirian; Prada, Patrícia O.; Ropelle, Eduardo R.; Hirabara, Sandro Massao; Castoldi, Ângela; Vieira, Pedro; Camara, Niels O. S.; Curi, Rui; Carvalheira, José B.; Saad, Mário J. A.

    2011-01-01

    Environmental factors and host genetics interact to control the gut microbiota, which may have a role in the development of obesity and insulin resistance. TLR2-deficient mice, under germ-free conditions, are protected from diet-induced insulin resistance. It is possible that the presence of gut microbiota could reverse the phenotype of an animal, inducing insulin resistance in an animal genetically determined to have increased insulin sensitivity, such as the TLR2 KO mice. In the present study, we investigated the influence of gut microbiota on metabolic parameters, glucose tolerance, insulin sensitivity, and signaling of TLR2-deficient mice. We investigated the gut microbiota (by metagenomics), the metabolic characteristics, and insulin signaling in TLR2 knockout (KO) mice in a non-germ free facility. Results showed that the loss of TLR2 in conventionalized mice results in a phenotype reminiscent of metabolic syndrome, characterized by differences in the gut microbiota, with a 3-fold increase in Firmicutes and a slight increase in Bacteroidetes compared with controls. These changes in gut microbiota were accompanied by an increase in LPS absorption, subclinical inflammation, insulin resistance, glucose intolerance, and later, obesity. In addition, this sequence of events was reproduced in WT mice by microbiota transplantation and was also reversed by antibiotics. At the molecular level the mechanism was unique, with activation of TLR4 associated with ER stress and JNK activation, but no activation of the IKKβ-IκB-NFκB pathway. Our data also showed that in TLR2 KO mice there was a reduction in regulatory T cell in visceral fat, suggesting that this modulation may also contribute to the insulin resistance of these animals. Our results emphasize the role of microbiota in the complex network of molecular and cellular interactions that link genotype to phenotype and have potential implications for common human disorders involving obesity, diabetes, and even other

  9. Potentiation of friend viral leukemogenesis by 9,10-dimethyl-1,2-benzanthracene in two strains of mice (41619)

    SciTech Connect

    Raikow, R.B.; Okunewick, J.P.; Jones, D.L.; Buffo, M.J.

    1983-01-01

    The polycyclic aromatic hydrocarbon, 9,10-dimethyl-1,2-benzanthracene (DMBA) produced malignancy involving the spleen in SJL/J and B10SJF1 mice when injected ip at 500 ..mu..g per mouse either alone or in combination with threshold doses of Friend leukemia virus (FLV). The mice that received both chemical and virus died significantly sooner than mice that received either chemical or virus alone, and a synergism between DMBA and FLV was demonstrated in both the virus-resistant B10SJF1 hybrids and virus-sensitive SJL/F mice. 23 references, 2 figures.

  10. Infectivity, Pathogenicity, and Virulence of Trypanosoma cruzi Isolates from Sylvatic Animals and Vectors, and Domestic Dogs from the United States in ICR Strain Mice and SD Strain Rats

    PubMed Central

    Roellig, Dawn M.; Yabsley, Michael J.

    2010-01-01

    Trypanosoma cruzi, the causative agent of Chagas disease, is widespread in the southern United States. In addition to detection in numerous wildlife host species, cases have been diagnosed in domestic dogs and humans. In the current investigation, groups of laboratory mice [Crl:CD1 (ICR)] were inoculated with one of 18 United States T. cruzi isolates obtained from a wide host range to elucidate their infectivity, pathogenicity, and virulence. In addition, laboratory rats (SD strain) were inoculated with four isolates. Mice and rats were susceptible to infection with all strains, but no morbidity or mortality was noted, which indicates that these T. cruzi isolates from the United States had low virulence for laboratory mice and rats. PMID:20810814

  11. [Incidence of alginate-coding gene in carbapenem-resistant Pseudomonas aeruginosa strains].

    PubMed

    Bogiel, Tomasz; Kwiecińska-Piróg, Joanna; Kozuszko, Sylwia; Gospodarek, Eugenia

    2011-01-01

    Pseudomonas aeruginosa rods are one of the most common isolated opportunistic nosocomial pathogens. Strains usually are capable to secret a capsule-like polysaccharide called alginate important for evasion of host defenses, especially during chronic pulmonary disease of patients with cystic fibrosis. Most genes for alginate biosynthesis and lysis are encoded by the operon. The aim of our study was to evaluate the incidence of algD sequence, generally use for alginate-coding gene detection, in 120 P. aeruginosa strains resistant to carbapenems. All isolates were obtained in the Department of Clinical Microbiology University Hospital no. 1 of dr A. Jurasz Collegium Medicum of L. Rydygier in Bydgoszcz Nicolaus Copernicus University in Toruń. Examined strains demonstrated resistance to carbenicillin (90,0%), ticarcillin (89,2%) and ticarcillin clavulanate (86,7%). All strains were susceptible to colistin. The majority of examined strains was susceptible to ceftazidime and cefepime (40,8% each) and norfloxacin (37,5%). Presence of algD gene - noted in 112 (93,3%) strains proves that not every strain is capable to produce alginate. It was also found out that differences in algD genes incidence in case of different clinical material that strains were isolated from were not statistically important. PMID:22184909

  12. Effects of Cinnabar on Pyrite Oxidation by Thiobacillus ferrooxidans and Cinnabar Mobilization by a Mercury-Resistant Strain

    PubMed Central

    Baldi, Franco; Olson, Gregory J.

    1987-01-01

    The effect of cinnabar on pyrite oxidation by mercury-sensitive and mercury-resistant strains of Thiobacillus ferrooxidans was investigated by using percolation columns. Mercury-resistant strains oxidized pyrite in pyrite-cinnabar mixtures (1 and 10%, wt/wt), whereas a mercury-sensitive strain did not. Elemental mercury was produced by the mercury-resistant strains growing in the pyrite-cinnabar mixtures in percolation columns and in flasks containing cinnabar only. Manometric experiments showed that cinnabar had little effect on oxygen uptake of mercury-sensitive or mercury-resistant cells growing on ferrous sulfate, pyrite, or pyrite-ferrous sulfate mixtures. In addition, shake flask leaching experiments showed that cinnabar had little effect on pyrite oxidation at 1% (wt/wt) but inhibited growth of mercury-sensitive and mercury-resistant strains at 10%. Mercury-resistant strains were unable to grow on cinnabar as an energy source. PMID:16347321

  13. Determination of antibiotic resistance pattern and bacteriocin sensitivity of Listeria monocytogenes strains isolated from different foods in turkey

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study aimed to determine the antibiotic resistance pattern and bacteriocin sensitivity of Listeria monocytogenes strains isolated from animal derived foods. With disc diffusion assay, all fourteen L. monocytogenes strains were susceptible to the antibiotics, including penicillin G, vancomycin, ...

  14. Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice

    PubMed Central

    Gruben, Nanda; Funke, Anouk; Kloosterhuis, Niels J.; Schreurs, Marijke; Sheedfar, Fareeba; Havinga, Rick; Houten, Sander M.; van de Sluis, Bart; Kuivenhoven, Jan Albert; Koonen, Debby P. Y.; Hofker, Marten H.

    2015-01-01

    Chronic inflammation is considered a causal risk factor predisposing to insulin resistance. However, evidence is accumulating that inflammation confined to the liver may not be causal to metabolic dysfunction. To investigate this, we assessed if hepatic inflammation explains the predisposition towards insulin resistance in low-density lipoprotein receptor knock-out (Ldlr−/−) mice. For this, wild type (WT) and Ldlr−/− mice were fed a chow diet, a high fat (HF) diet, or a high fat, high cholesterol (HFC) diet for 2 weeks. Plasma lipid levels were elevated in chow-fed Ldlr−/− mice compared to WT mice. Although short-term HF or HFC feeding did not result in body weight gain and adipose tissue inflammation, dyslipidemia was worsened in Ldlr−/− mice compared to WT mice. In addition, dyslipidemic HF-fed Ldlr−/− mice had a higher hepatic glucose production rate than HF-fed WT mice, while peripheral insulin resistance was unaffected. This suggests that HF-fed Ldlr−/− mice suffered from hepatic insulin resistance. While HFC-fed Ldlr−/− mice displayed the anticipated increased hepatic inflammation, this did neither exacerbate systemic nor hepatic insulin resistance. Therefore, our results show that hepatic insulin resistance is unrelated to cholesterol-induced hepatic inflammation in Ldlr−/− mice, indicating that hepatic inflammation may not contribute to metabolic dysfunction per se. PMID:25815343

  15. [Effects of constant low temperature on cold resistance of different strains Polygonatum odoratum].

    PubMed

    Wang, Er-Huan; Xu, Yong-Hua; Zhand, Zhong-Bao; Xu, Dian-Wen; Xi, Guang-Sheng; Zhang, Lian-Xue

    2015-01-01

    In this paper, the five strains of Polygonatum odoratum were used as the experimental materials to test the supercooling point, freezing point, the degree of supercooling, the transition stage time, cooling time and water composition of the plant tissue. The cold resistance of P. odoratum was analyzed with the Gray Correlation Method. The results showed that the cold resistances of the five strains of P. odoratum were different, and the water content of plant tissue had some relevance with freezing point and supercooling point, whereas, it could not be measured when the moisture content was too low. The order of cold resistance of the five strains of P. odoratum was ZJCY, DYYZ, XYYZ, CYYZ and JZ I. PMID:25993790

  16. Tetracycline-resistant L-forms isolated from an antibiotic-susceptible strain of Listeria monocytogenes.

    PubMed Central

    Schmitt-Slomska, J; Marmouset, M C; Louis, C; Bally, R; Starka, G; Madoff, S

    1982-01-01

    A tetracycline-susceptible strain of Listeria monocytogenes type 4b was converted to stable L-forms by penicillin. L-form variants resistant to tetracycline were then selected from a predominantly tetracycline-susceptible L-form population on plates containing penicillin and increasing concentrations of tetracycline. The origin of tetracycline-resistant L-forms from the parent Listeria strain was confirmed biochemically, by immunofluorescence, and by polyacrylamide gel electrophoresis. Scanning and transmission electron microscopy confirmed the typical L-form structure and the complete lack of cell wall in both L-form strains. The level of [3H]tetracycline uptake was lower in tetracycline-resistant than in susceptible cells. Images PMID:6817706

  17. Resistin Induces Hypertension and Insulin Resistance in Mice via a TLR4-Dependent Pathway.

    PubMed

    Jiang, Yun; Lu, Linfang; Hu, Youtao; Li, Qiang; An, Chaoqiang; Yu, Xiaolan; Shu, Le; Chen, Ao; Niu, Congcong; Zhou, Lei; Yang, Zaiqing

    2016-01-01

    Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4(-/-) mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4(-/-) mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension. PMID:26917360

  18. Resistin Induces Hypertension and Insulin Resistance in Mice via a TLR4-Dependent Pathway

    PubMed Central

    Jiang, Yun; Lu, Linfang; Hu, Youtao; Li, Qiang; An, Chaoqiang; Yu, Xiaolan; Shu, Le; Chen, Ao; Niu, Congcong; Zhou, Lei; Yang, Zaiqing

    2016-01-01

    Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4−/− mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4−/− mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension. PMID:26917360

  19. Perfluorooctanoic acid (PFOA)-induced liver lesions in two strains of mice following developmental exposures: PPARα is not required

    PubMed Central

    Filgo, Adam J.; Quist, Erin M.; Hoenerhoff, Mark J.; Brix, Amy E.; Kissling, Grace E.; Fenton, Suzanne E.

    2014-01-01

    Perfluorooctanoate acid (PFOA) is a ubiquitous pollutant that causes liver toxicity in rodents, a process believed to be dependent on peroxisome proliferation activated receptor alpha (PPARα) activation. Differences between humans and rodents have made the human relevance of some health effects caused by PFOA controversial. We analyzed liver toxicity at 18 months following gestational PFOA exposure in CD-1 and 129/Sv strains of mice and compared PFOA-induced effects between strains and in wild type (WT) and PPARα-knockout (KO) 129/Sv mice. Pregnant mice were exposed daily to doses (0.01–5mg/kg/BW) of PFOA from gestation days 1–17. The female offspring were necropsied at 18 months and liver sections underwent a full pathology review. Hepatocellular adenomas formed in PFOA-exposed PPARα-KO 129/Sv and CD-1 mice, and were absent in untreated controls from those groups and WT 129/Sv. Hepatocellular hypertrophy was significantly increased by PFOA exposure in CD-1 and an increased severity was found in WT 129/Sv mice. PFOA significantly increased non-neoplastic liver lesions in PPARα-KO mice (hepatocyte hypertrophy, bile duct hyperplasia and hematopoietic cell proliferation). Low dose gestational exposures to PFOA induced latent PPARα independent liver toxicity that was observed in aged mice. Evidence of liver toxicity in PPARα-KO mice warrants further investigation into PPARα independent pathways. PMID:25398757

  20. Abrupt Emergence of a Single Dominant Multidrug-Resistant Strain of Escherichia coli

    PubMed Central

    Johnson, James R.; Tchesnokova, Veronika; Johnston, Brian; Clabots, Connie; Roberts, Pacita L.; Billig, Mariya; Riddell, Kim; Rogers, Peggy; Qin, Xuan; Butler-Wu, Susan; Price, Lance B.; Aziz, Maliha; Nicolas-Chanoine, Marie-Hélène; DebRoy, Chitrita; Robicsek, Ari; Hansen, Glen; Urban, Carl; Platell, Joanne; Trott, Darren J.; Zhanel, George; Weissman, Scott J.; Cookson, Brad T.; Fang, Ferric C.; Limaye, Ajit P.; Scholes, Delia; Chattopadhyay, Sujay; Hooper, David C.; Sokurenko, Evgeni V.

    2013-01-01

    Background. Fluoroquinolone-resistant Escherichia coli are increasingly prevalent. Their clonal origins—potentially critical for control efforts—remain undefined. Methods. Antimicrobial resistance profiles and fine clonal structure were determined for 236 diverse-source historical (1967–2009) E. coli isolates representing sequence type ST131 and 853 recent (2010–2011) consecutive E. coli isolates from 5 clinical laboratories in Seattle, Washington, and Minneapolis, Minnesota. Clonal structure was resolved based on fimH sequence (fimbrial adhesin gene: H subclone assignments), multilocus sequence typing, gyrA and parC sequence (fluoroquinolone resistance-determining loci), and pulsed-field gel electrophoresis. Results. Of the recent fluoroquinolone-resistant clinical isolates, 52% represented a single ST131 subclonal lineage, H30, which expanded abruptly after 2000. This subclone had a unique and conserved gyrA/parC allele combination, supporting its tight clonality. Unlike other ST131 subclones, H30 was significantly associated with fluoroquinolone resistance and was the most prevalent subclone among current E. coli clinical isolates, overall (10.4%) and within every resistance category (11%–52%). Conclusions. Most current fluoroquinolone-resistant E. coli clinical isolates, and the largest share of multidrug-resistant isolates, represent a highly clonal subgroup that likely originated from a single rapidly expanded and disseminated ST131 strain. Focused attention to this strain will be required to control the fluoroquinolone and multidrug-resistant E. coli epidemic. PMID:23288927

  1. Benomyl-resistant mutant strain of Trichoderma sp. with increased mycoparasitic activity.

    PubMed

    Olejníková, P; Ondrusová, Z; Krystofová, S; Hudecová, D

    2010-01-01

    Application of UV radiation to the strain Trichoderma sp. T-bt (isolated from lignite) resulted in the T-brm mutant which was resistant to the systemic fungicide benomyl. The tub2 gene sequence in the T-brm mutant differed from the parent as well as the collection strain (replacing tyrosine with histidine in the TUB2 protein). Under in vitro conditions this mutant exhibited a higher mycoparasitic activity toward phytopathogenic fungi. PMID:20336512

  2. A highly sensitive flexible strain sensor based on the contact resistance change of carbon nanotube bundles

    NASA Astrophysics Data System (ADS)

    Song, Youngsup; Lee, Jae-Ik; Pyo, Soonjae; Eun, Youngkee; Choi, Jungwook; Kim, Jongbaeg

    2016-05-01

    A novel carbon nanotube (CNT)-based flexible strain sensor with the highest gauge factor of 4739 is presented. CNT-to-CNT contacts are fabricated on a pair of silicon electrodes fixed on a PDMS specimen for both flexibility and electrical connection. The strain is detected by the resistance change between facing CNT bundles. The proposed approach could be applied for diverse applications with a high gauge factor.

  3. Macrophages Are the Determinant of Resistance to and Outcome of Nonlethal Babesia microti Infection in Mice

    PubMed Central

    Terkawi, Mohamad Alaa; Cao, Shinuo; Herbas, Maria S.; Nishimura, Maki; Li, Yan; Moumouni, Paul Franck Adjou; Pyarokhil, Asadullah Hamid; Kondoh, Daisuke; Kitamura, Nobuo; Nishikawa, Yoshifumi; Kato, Kentaro; Yokoyama, Naoaki; Zhou, Jinlin; Suzuki, Hiroshi; Igarashi, Ikuo

    2014-01-01

    In the present study, we examined the contributions of macrophages to the outcome of infection with Babesia microti, the etiological agent of human and rodent babesiosis, in BALB/c mice. Mice were treated with clodronate liposome at different times during the course of B. microti infection in order to deplete the macrophages. Notably, a depletion of host macrophages at the early and acute phases of infection caused a significant elevation of parasitemia associated with remarkable mortality in the mice. The depletion of macrophages at the resolving and latent phases of infection resulted in an immediate and temporal exacerbation of parasitemia coupled with mortality in mice. Reconstituting clodronate liposome-treated mice at the acute phase of infection with macrophages from naive mice resulted in a slight reduction in parasitemia with improved survival compared to that of mice that received the drug alone. These results indicate that macrophages play a crucial role in the control of and resistance to B. microti infection in mice. Moreover, analyses of host immune responses revealed that macrophage-depleted mice diminished their production of Th1 cell cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Furthermore, depletion of macrophages at different times exaggerated the pathogenesis of the infection in deficient IFN-γ−/− and severe combined immunodeficiency (SCID) mice. Collectively, our data provide important clues about the role of macrophages in the resistance and control of B. microti and imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function. PMID:25312951

  4. [Treatment with arbekacin of surgical infections by resistant strains of Staphylococcus aureus. Arbekacin Study Group].

    PubMed

    Morimoto, K; Nakatani, S; Kaji, M; Kinoshita, H; Fujimoto, M; Hirata, S; Ueda, T; Tamate, S; Yamazaki, O

    1994-06-01

    The frequency of infection by methicillin-resistant Staphylococcus aureus (MRSA) is high in Japan and control of such strains is urgently needed. Arbekacin (ABK), a semisynthetic aminoglycoside, has potent activity against S. aureus, including resistant strains, and against Gram-negative bacteria as well. For this reason, in surgical infections (which are often caused by more than one bacterium), this drug might be particularly effective. We calculated the MIC and the decrease in the MIC when cultures of 59 resistant strains of S. aureus isolated in our wards at Osaka City University Hospital, contained arbekacin in the medium. We also used the drug to treat 12 infections caused by resistant strains of S. aureus. The MICs of vancomycin had a single peak at 0.5 microgram/ml, and those for ABK had double peaks at 0.5 and 4.0 micrograms/ml. The effect of arbekacin in lowering the MIC of minocycline (MINO) was slight because of the low MIC of MINO. Effects on fosfomycin (FOM), ampicillin, clavulanic acid/ticarcillin, cefotiam, cefuzonam, flomoxef, and imipenem/cilastatin were strong; the peaks were lowered by 1/2(7)-1/2(11). When 1.0 micrograms/ml ABK was present in the medium, the efficacy of FOM was increased enough that, by prediction from the pharmacokinetics of FOM (blood level when given at the usual dose), all but one (2%) of the 47 resistant strains would be eradicated clinically. If 2.0 micrograms/ml ABK were in the medium, all strain would be eradicated, by our calculations. We treated 11 infections and one colonization by resistant strains of S. aureus with ABK and evaluated the response in these cases of infection. Four infections were treated with FOM as well. The clinical efficacy was good in four infections (three patients), fair in four, and poor in three, for an efficacy rate of 36%. All presumed causative bacteria were eradicated in two (18%) of the 11 infections and S. aureus strains were eradicated in three (27%) of the 11 infections. No symptoms of

  5. Neurochemical measurement of adenosine in discrete brain regions of five strains of inbred mice.

    PubMed

    Pani, Amar K; Jiao, Yun; Sample, Kenneth J; Smeyne, Richard J

    2014-01-01

    Adenosine (ADO), a non-classical neurotransmitter and neuromodulator, and its metabolites adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP), have been shown to play an important role in a number of biochemical processes. Although their signaling is well described, it has been difficult to directly, accurately and simultaneously quantitate these purines in tissue or fluids. Here, we describe a novel method for measuring adenosine (ADO) and its metabolites using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Using this chromatographic technique, we examined baseline levels of ADO and ATP, ADP and AMP in 6 different brain regions of the C57BL/6J mouse: stratum, cortex, hippocampus, olfactory bulb, substantia nigra and cerebellum and compared ADO levels in 5 different strains of mice (C57BL/6J, Swiss-Webster, FVB/NJ, 129P/J, and BALB/c). These studies demonstrate that baseline levels of purines vary significantly among the brain regions as well as between different mouse strains. These dissimilarities in purine concentrations may explain the variable phenotypes among background strains described in neurological disease models. PMID:24642754

  6. Screening of Herbal-Based Bioactive Extract Against Carbapenem-Resistant Strain of Acinetobacter baumannii.

    PubMed

    Tiwari, Monalisa; Roy, Ranita; Tiwari, Vishvanath

    2016-07-01

    Acinetobacter baumannii is grouped in the ESKAPE pathogens by Infectious Disease Society of America, which is linked to high degree of morbidity, mortality, and increased costs. The high level of acquired and intrinsic resistance mechanisms of these bacteria makes it an urgent requirement to find a suitable alternative to carbapenem, a commonly prescribed drug for Acinetobacter infection. In this study, methanolic extracts of six medicinal plants were subjected to phytochemical screening and their antimicrobial activity was tested against two strains of A. baumannii (ATCC 19606, carbapenem-sensitive strain, and RS 307, carbapenem-resistant strain). Synergistic effect of the plant extracts and antibiotics was also tested. Bael or Aegle marmelos contains tannin, phenol, terpenoids, glycoside, alkaloids, coumarine, steroid, and quinones. Flowers of madar or Calotropis procera possess tannin, phenol, terpenoids, glycoside, quinone, anthraquinone, anthocyanin, coumarin, and steroid. An inhibitory growth curve was seen for both the bacterial strains when treated with A. marmelos, Curcuma longa, and leaves and flowers of C. procera. Antibiotics alone showed a small zone of inhibition, but when used with herbal extracts they exhibited larger zone of inhibition. Synergistic effect of A. marmelos and imipenem was the best against both the strains of A. baumannii. From this study, it can be concluded that extracts from A. marmelos and leaves and flowers of C. procera exhibited the most effective antibacterial activity. These herbal extracts may be used to screen the bioactive compound against the carbapenem-resistant strain of A. baumannii. PMID:26910023

  7. The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice.

    PubMed

    Tousen, Yuko; Matsumoto, Yu; Matsumoto, Chiho; Nishide, Yoriko; Nagahata, Yuya; Kobayashi, Isao; Ishimi, Yoshiko

    2016-07-01

    Equol is a metabolite of the soya isoflavone (ISO) daidzein that is produced by intestinal microbiota. Equol has greater oestrogenic activity compared with other ISO, and it prevents bone loss in postmenopausal women. Resistant starch (RS), which has a prebiotic activity and is a dietary fibre, was reported to promote equol production. Conversely, the intestinal microbiota is reported to directly regulate bone health by reducing inflammatory cytokine levels and T-lymphocytes in bone. The present study evaluated the combined effects of diet supplemented with ISO and RS on intestinal microbiota, equol production, bone mineral density (BMD) and inflammatory gene expression in the bone marrow of ovariectomised (OVX) mice. Female ddY strain mice, aged 8 weeks, were either sham-operated (Sham, n 7) or OVX. OVX mice were randomly divided into the following four groups (seven per group): OVX control (OVX); OVX fed 0·05 % ISO diet (OVX+ISO); OVX fed 9 % RS diet (OVX+RS); and OVX fed 0·05 % ISO- and 9 % RS diet (OVX+ISO+RS). After 6 weeks, treatment with the combination of ISO and RS increased equol production, prevented the OVX-induced decline in trabecular BMD in the distal femur by modulating the enteric environment and altered OVX-induced inflammation-related gene expression in the bone marrow. However, there were no significant differences in bone parameters between the ISO+RS and ISO-alone groups in OVX mice. Our findings suggest that the combination of ISO and RS might alter intestinal microbiota and immune status in the bone marrow, resulting in attenuated bone resorption in OVX mice. PMID:27197747

  8. Crif1 Deficiency Reduces Adipose OXPHOS Capacity and Triggers Inflammation and Insulin Resistance in Mice

    PubMed Central

    Ryu, Min Jeong; Kim, Soung Jung; Kim, Yong Kyung; Choi, Min Jeong; Tadi, Surendar; Lee, Min Hee; Lee, Seong Eun; Chung, Hyo Kyun; Jung, Saet Byel; Kim, Hyun-Jin; Jo, Young Suk; Kim, Koon Soon; Lee, Sang-Hee; Kim, Jin Man; Kweon, Gi Ryang; Park, Ki Cheol; Lee, Jung Uee; Kong, Young Yun; Lee, Chul-Ho; Chung, Jongkyeong; Shong, Minho

    2013-01-01

    Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS–deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA–encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance. PMID:23516375

  9. Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis

    PubMed Central

    Baumgartl, Julia; Baudler, Stephanie; Scherner, Maximilian; Babaev, Vladimir; Makowski, Liza; Suttles, Jill; McDuffie, Marcia; Fazio, Sergio; Kahn, C. Ronald; Hotamisligil, Gökhan S.; Krone, Wilhelm; Linton, MacRae; Brüning, Jens C.

    2014-01-01

    Summary Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineagespecific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1β expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2–/–ApoE–/– cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis. PMID:16581002

  10. Linezolid-resistant Staphylococcus aureus strain 1128105, the first known clinical isolate possessing the cfr multidrug resistance gene.

    PubMed

    Locke, Jeffrey B; Zuill, Douglas E; Scharn, Caitlyn R; Deane, Jennifer; Sahm, Daniel F; Denys, Gerald A; Goering, Richard V; Shaw, Karen J

    2014-11-01

    The Cfr methyltransferase confers resistance to six classes of drugs which target the peptidyl transferase center of the 50S ribosomal subunit, including some oxazolidinones, such as linezolid (LZD). The mobile cfr gene was identified in European veterinary isolates from the late 1990s, although the earliest report of a clinical cfr-positive strain was the 2005 Colombian methicillin-resistant Staphylococcus aureus (MRSA) isolate CM05. Here, through retrospective analysis of LZD(r) clinical strains from a U.S. surveillance program, we identified a cfr-positive MRSA isolate, 1128105, from January 2005, predating CM05 by 5 months. Molecular typing of 1128105 revealed a unique pulsed-field gel electrophoresis (PFGE) profile most similar to that of USA100, spa type t002, and multilocus sequence type 5 (ST5). In addition to cfr, LZD resistance in 1128105 is partially attributed to the presence of a single copy of the 23S rRNA gene mutation T2500A. Transformation of the ∼37-kb conjugative p1128105 cfr-bearing plasmid from 1128105 into S. aureus ATCC 29213 background strains was successful in recapitulating the Cfr antibiogram, as well as resistance to aminoglycosides and trimethoprim. A 7-kb cfr-containing region of p1128105 possessed sequence nearly identical to that found in the Chinese veterinary Proteus vulgaris isolate PV-01 and in U.S. clinical S. aureus isolate 1900, although the presence of IS431-like sequences is unique to p1128105. The cfr gene environment in this early clinical cfr-positive isolate has now been identified in Gram-positive and Gram-negative strains of clinical and veterinary origin and has been associated with multiple mobile elements, highlighting the versatility of this multidrug resistance gene and its potential for further dissemination. PMID:25155597

  11. Printed resistive strain sensors for monitoring of light-weight structures

    NASA Astrophysics Data System (ADS)

    Rausch, J.; Salun, L.; Griesheimer, S.; Ibis, M.; Werthschützky, R.

    2011-04-01

    In this paper we present the design and test of printed strain sensors, which can be integrated in light-weight structures for monitoring purposes. We focus on composite structures consisting of metal substrate as well as insulating and conductive ink layers for sensing normal strain at the surface. Both, inkjet and screen printing technology are used to realize resistive topologies that can be evaluated using a Wheatstone bridge configuration. In a first step, we analyze electrical properties of functional inks: electrical impedance and breakdown electrical field strength in case of insulation inks, resistance in case of conducting inks. Silver and PEDOT:PSS based suspensions are printed as sensing layer. To determine the resistance change due to plastic deformation of the metal substrate, tensile tests are performed up to 30% strain and subsequent resistance change is measured. In a second step, the sensing effect of printed conductive structures is investigated. Resistive sensing topologies are designed for detecting longitudinal and transversal normal strain. Meander structures, which form single resistors as well as bridge configurations, are printed on test specimens and analyzed in a four-point bending set up. Performing loading and unloading cycles, gauge factor, cross sensitivity, nonlinearity and hysteresis error of the sensors are measured.

  12. High-Temperature Extensometry and PdCr Temperature-Compensated Wire Resistance Strain Gages Compared

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A detailed experimental evaluation is underway at the NASA Lewis Research Center to compare and contrast the performance of the PdCr/Pt dual-element temperature-compensated wire resistance strain gage with that of conventional high-temperature extensometry. The advanced PdCr gage, developed by researchers at Lewis, exhibits desirable properties and a relatively small and repeatable apparent strain to 800 C. This gage represents a significant advance in technology because existing commercial resistance strain gages are not reliable for quasi-static strain measurements above approx. 400 C. Various thermal and mechanical loading spectra are being applied by a high-temperature thermomechanical uniaxial testing system to evaluate the two strain-measurement systems. This is being done not only to compare and contrast the two strain sensors, but also to investigate the applicability of the PdCr strain gage to the coupon-level specimen testing environment typically employed when the high-temperature mechanical behavior of structural materials is characterized. Strain measurement capabilities to 800 C are being investigated with a nickel-base superalloy, Inconel 100 (IN 100), substrate material and application to TMC's is being examined with the model system, SCS-6/Ti-15-3. Furthermore, two gage application techniques are being investigated in the comparison study: namely, flame-sprayed and spot welding. The apparent strain responses of both the weldable and flame-sprayed PdCr wire strain gages were found to be cyclically repeatable on both IN 100 and SCS-6/Ti-15-3 [0]_8. In general, each gage exhibited some uniqueness with respect to apparent strain behavior. Gages mounted on the IN 100 specimens tended to show a repeatable apparent strain within the first few cycles, because the thermal response of IN 100 was stable. This was not the case, however, for the TMC specimens, which typically required several thermal cycles to stabilize the thermal strain response. Thus

  13. Resistance gene pool to co-trimoxazole in non-susceptible Nocardia strains

    PubMed Central

    Valdezate, Sylvia; Garrido, Noelia; Carrasco, Gema; Villalón, Pilar; Medina-Pascual, María J.; Saéz-Nieto, Juan A.

    2015-01-01

    The soil-borne pathogen Nocardia sp. causes severe cutaneous, pulmonary, and central nervous system infections. Against them, co-trimoxazole (SXT) constitutes the mainstay of antimicrobial therapy. However, some Nocardia strains show resistance to SXT, but the underlying genetic basis is unknown. We investigated the presence of genetic resistance determinants and class 1–3 integrons in 76 SXT-resistant Nocardia strains by PCR and sequencing. By E test, these clinical strains showed SXT minimum inhibitory concentrations of ≥32:608 mg/L (ratio of 1:19 for trimethoprim: sulfamethoxazole). They belonged to 12 species, being the main representatives Nocardia farcinica (32%), followed by N. flavorosea (6.5%), N. nova (11.8%), N. carnea (10.5%), N. transvalensis (10.5%), and Nocardia sp. (6.5%). The prevalence of resistance genes in the SXT-resistant strains was as follows: sul1 and sul2 93.4 and 78.9%, respectively, dfrA(S1) 14.7%, blaTEM-1 and blaZ 2.6 and 2.6%, respectively, VIM-2 1.3%, aph(3′)-IIIa 40.8%, ermA, ermB, mefA, and msrD 2.6, 77.6, 14.4, and 5.2%, respectively, and tet(O), tet(M), and tet(L) 48.6, 25.0, and 3.9%, respectively. Detected amino acid changes in GyrA were not related to fluoroquinolone resistance, but probably linked to species polymorphism. Class 1 and 3 integrons were found in 93.42 and 56.57% strains, respectively. Class 2 integrons and sul3 genes were not detected. Other mechanisms, different than dfrA(S1), dfrD, dfrF, dfrG, and dfrK, could explain the strong trimethoprim resistance shown by the other 64 strains. For first time, resistance determinants commonly found in clinically important bacteria were detected in Nocardia sp. sul1, sul2, erm(B), and tet(O) were the most prevalent in the SXT-resistant strains. The similarity in their resistome could be due to a common genetic platform, in which these determinants are co-transferred. PMID:25972856

  14. Resistant Shigella strains in refugees, August-October 2015, Greece.

    PubMed

    Georgakopoulou, T; Mandilara, G; Mellou, K; Tryfinopoulou, K; Chrisostomou, A; Lillakou, H; Hadjichristodoulou, C; Vatopoulos, A

    2016-08-01

    Shigellosis is endemic in most developing countries and thus a known risk in refugees and internally displaced persons. In 2015, a massive influx of refugees into Greece, due to the political crisis in the Middle East, led to the development of appropriate conditions for outbreaks of communicable diseases as shigellosis. We present a cluster of 16 shigellosis cases in refugees, detected by the implementation of a syndromic notification system in one transit centre in Athens, between 20 August and 7 October 2015. Both Shigella flexneri (n = 8) and S. sonnei (n = 8) were identified, distributed in various serotypes. All tested isolates (n = 13) were multidrug resistant; seven were CTX-M-type extended-spectrum β-lactamase producers. Our results indicate lack of a potential common source, although pulsed-field gel electrophoresis typing results revealed small clusters in isolates of the same serotype indicating possible limited person-to-person transmission without identifying secondary community cases related to the refugees. To prevent the spread of shigellosis, empirical antibiotic treatment as well as environmental hygiene measures were implemented. The detection of multi-drug resistance is important for determining the appropriate empirical antibiotic treatment for the more severe cases, while at the same time real-time typing is useful for epidemiological investigation and control measures. PMID:27180973

  15. Association of tcdA+/tcdB+ Clostridium difficile Genotype with Emergence of Multidrug-Resistant Strains Conferring Metronidazole Resistant Phenotype

    PubMed Central

    Shayganmehr, Farahnaz-Sadat; Alebouyeh, Masoud; Azimirad, Masoumeh; Aslani, Mohammad Mehdi; Zali, Mohammad Reza

    2015-01-01

    Background: Reduced susceptibility of Clostridium difficile to antibiotics is problematic in clinical settings. There is new evidence indicating the cotransfer of toxin-encoding genes and conjugative transposons encoding resistance to antibiotics among different C. difficile strains. To analyze this association, in the current study, we evaluated the frequency of toxigenic C. difficile among the strains with different multidrug-resistant (MDR) profiles in Iran. Methods: Antimicrobial susceptibility patterns and minimal inhibitory concentrations (MIC) of the isolates were determined against metronidazole, imipenem, ceftazidime, amikacin, and ciprofloxacin by agar dilution method. The association of the resistance profiles and toxigenicity of the strains were studied by PCR targeting tcdA and tcdB genes. Results: Among 86 characterized strains, the highest and lowest resistance rates were related to ciprofloxacin (97%) and metronidazole (5%), respectively. The frequency of resistance to other antibiotics was as follow: imipenem (48%), ceftazidime (76%), and amikacin (76.5%). Among the resistant strains, double drug resistance and MDR phenotypes were detected in the frequencies of 10.4% and 66.2%, respectively. All of the metronidazole-resistant strains belonged to tcdA +/tcdB + genotype with triple or quintuple drug resistance phenotypes. MIC50 and MIC90 for this antibiotic was equally ≤ 8 μg/ml. Conclusion: These results proposed the association of tcdA +/tcdB + genotype of C. difficile and the emergence of resistance strains to broad-spectrum antibiotics and metronidazole. PMID:26048022

  16. Site-specific Genome Editing in PBMCs With PLGA Nanoparticle-delivered PNAs Confers HIV-1 Resistance in Humanized Mice

    PubMed Central

    Schleifman, Erica B; McNeer, Nicole Ali; Jackson, Andrew; Yamtich, Jennifer; Brehm, Michael A; Shultz, Leonard D; Greiner, Dale L; Kumar, Priti; Saltzman, W Mark; Glazer, Peter M

    2013-01-01

    Biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulating triplex-forming peptide nucleic acids (PNAs) and donor DNAs for recombination-mediated editing of the CCR5 gene were synthesized for delivery into human peripheral blood mononuclear cells (PBMCs). NPs containing the CCR5-targeting molecules efficiently entered PBMCs with low cytotoxicity. Deep sequencing revealed that a single treatment with the formulation resulted in a targeting frequency of 0.97% in the CCR5 gene and a low off-target frequency of 0.004% in the CCR2 gene, a 216-fold difference. NP-treated PBMCs efficiently engrafted immunodeficient NOD-scid IL-2rγ-/- mice, and the targeted CCR5 modification was detected in splenic lymphocytes 4 weeks posttransplantation. After infection with an R5-tropic strain of HIV-1, humanized mice with CCR5-NP–treated PBMCs displayed significantly higher levels of CD4+ T cells and significantly reduced plasma viral RNA loads compared with control mice engrafted with mock-treated PBMCs. This work demonstrates the feasibility of PLGA-NP–encapsulated PNA-based gene-editing molecules for the targeted modification of CCR5 in human PBMCs as a platform for conferring HIV-1 resistance. PMID:24253260

  17. Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice.

    PubMed

    Oyama, Takuto; Miyazaki, Motoyasu; Yoshimura, Michinobu; Takata, Tohru; Ohjimi, Hiroyuki; Jimi, Shiro

    2016-01-01

    Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA). MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high-biofilm formers (H-BF) and low-biofilm formers (L-BF). These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections. PMID:27376326

  18. Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice

    PubMed Central

    Oyama, Takuto; Miyazaki, Motoyasu; Yoshimura, Michinobu; Takata, Tohru; Ohjimi, Hiroyuki; Jimi, Shiro

    2016-01-01

    Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA). MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high-biofilm formers (H-BF) and low-biofilm formers (L-BF). These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections. PMID:27376326

  19. [Evolution of resistance in the genus Enterococcus in strains isolated from blood].

    PubMed

    Peset, V; Ubeda, P; Sarrión, A; Pérez-Bellés, C; Cantón, E; Córdoba, J; Gobernado, M

    1998-12-01

    The objective of this study was to determine the evolution of the species distribution and the prevalence of resistance to the Enterococcus genus. We studied 281 strains of enterococcus isolated from blood samples: 90 throughout 1984 and 791 from the years 1994 to 1996. identification was made using PosCombo 4Y Microscan-Baxter dehydrated panels and the Rapid ID 32 Strep system (bioMerieux). The MICs were calculated using the agar dilution method according to recommendations of the NCCLS for the following antibiotics: ampicillin, vancomycin, teicoplanin, gentamicin, kanamycin and streptomycin. The production of betalactamases were evaluated using a paper disk with nitrocefin for all the strains. The genotypes with resistance to glycopeptides were determined using PCR. The percentage of E. faecalis for 1984-1986/1994-1996 was 82.2/79.4; of E. faecium 4.4/16.4; and other species 12.214.3. The resistance to ampicillin went from 1.1% to 5.8%; high level resistance to glycopeptides went from 0% to 9.9%; for low level from 7.7% to 2.6%; resistance to a high charge of gentamicin went from 27.7% to 40.8%; and that for kanamycin from 45.5% to 62.8%. Resistance to streptomycin remained constant (45.5%). No strains produced betalactamases. For the species E. faecium, a statistically significant increase was detected for global resistance to ampicillin, gentamicin and kanamycin, with resistance to streptomycin remaining at similar percentages. No high level resistance to glycopeptides was detected in the first time period, but the low level resistance was greater. PMID:10336313

  20. Intermedin Restores Hyperhomocysteinemia-induced Macrophage Polarization and Improves Insulin Resistance in Mice.

    PubMed

    Pang, Yanli; Li, Yang; Lv, Ying; Sun, Lulu; Zhang, Songyang; Li, Yin; Wang, Yuhui; Liu, George; Xu, Ming-Jiang; Wang, Xian; Jiang, Changtao

    2016-06-01

    Hyperhomocysteinemia (HHcy) is a condition characterized by an abnormally high level of homocysteine, an inflammatory factor. This condition has been suggested to promote insulin resistance. To date, the underlying molecular mechanism remains largely unknown, and identifying novel therapeutic targets for HHcy-induced insulin resistance is of high priority. It is well known that intermedin (IMD), a calcitonin family peptide, exerts potent anti-inflammatory effects. In this study, the effects of IMD on HHcy-induced insulin resistance were investigated. Glucose tolerance and insulin tolerance tests were performed on mice treated with IMD by minipump implantation (318 ng/kg/h for 4 weeks) or adipocyte-specific IMD overexpression mice (Adipo-IMD transgenic mice). The expression of genes and proteins related to M1/M2 macrophages and endoplasmic reticulum stress (ERS) was evaluated in adipose tissues or cells. The expression of IMD was identified to be lower in the plasma and adipose tissues of HHcy mice. In both IMD treatment by minipump implantation and Adipo-IMD transgenic mice, IMD reversed HHcy-induced insulin resistance, as revealed by glucose tolerance and insulin tolerance tests. Further mechanistic study revealed that IMD reversed the Hcy-elevated ratio of M1/M2 macrophages by inhibiting AMP-activated protein kinase activity. Adipo-IMD transgenic mice displayed reduced ERS and lower inflammation in adipose tissues with HHcy. Soluble factors from Hcy-treated macrophages induced adipocyte ERS, which was reversed by IMD treatment. These findings revealed that IMD treatment restores the M1/M2 balance, inhibits chronic inflammation in adipose tissues, and improves systemic insulin sensitivity of HHcy mice. PMID:27080257

  1. Draft Genome Sequence of a Clinically Isolated Extensively Drug-Resistant Pseudomonas aeruginosa Strain

    PubMed Central

    Manivannan, Bhavani; Mahalingam, Niranjana; Jadhao, Sudhir; Mishra, Amrita; Nilawe, Pravin

    2016-01-01

    We present the draft genome assembly of an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain isolated from a patient with a history of genito urinary tuberculosis. The draft genome is 7,022,546 bp with a G+C content of 65.48%. It carries 7 phage genomes, genes for quorum sensing, biofilm formation, virulence, and antibiotic resistance. PMID:27013045

  2. Mice lacking macrophage 12/15-lipoxygenase are resistant to experimental hypertension

    PubMed Central

    Cepura, Cody; Magier, Devora; Siangjong, Lawan; Gauthier, Kathryn M.; Campbell, William B.

    2012-01-01

    In mouse arteries, Alox15 [leukocyte-type 12/15-lipoxygenase (LO)] is assumed to regulate vascular function by metabolizing arachidonic acid (AA) to dilator eicosanoids that mediate the endothelium-dependent relaxations to AA and acetylcholine (ACh). We used Alox15−/− mice, made by targeted disruption of the Alox15 gene, to characterize its role in the regulation of blood pressure and vascular tone. Systolic blood pressures did not differ between wild-type (WT) and Alox15−/− mice between 8–12 wk of age, but Alox15−/− mice exhibited resistance toward both NG-nitro-l-arginine-methyl ester (l-NAME)- and deoxycorticosterone acetate (DOCA)/high-salt-induced hypertension. ACh relaxed mesenteric arteries and abdominal aortas of WT and Alox15−/− mice to an identical extent. The LO inhibitor nordihydroguaiaretic acid attenuated the ACh relaxations by 35% in arteries from both WT and Alox15−/− mice. Reverse-phase HPLC analysis of [14C]AA metabolites in aorta and peritoneal macrophages (PM) revealed differences. Unlike PM, aorta tissue did not produce detectable amounts of 15-hydroxyeicosatetraenoic acid. Although Alox15 mRNA was detected in aorta, high-resolution gel electrophoresis with immunodetection revealed no Alox15 protein expression. Unlike aorta, Alox15 protein was detected in PM, intestine, fat, lung, spleen, and skin from WT, but not Alox15−/−, mice. Injection of WT PM, a primary source of Alox15 protein, into Alox15−/− mice abolished their resistance toward l-NAME-induced hypertension. On the other hand, WT mice acquired resistance to l-NAME-induced hypertension after depletion of macrophages by clodronate injection. These studies indicate that Alox15 is involved in development of experimental hypertension by altering macrophage functions but not via synthesis of the vasoactive LO metabolites in mouse arteries. PMID:22467300

  3. Carnitine Palmitoyltransferase 1b Deficient Mice Develop Severe Insulin Resistance After Prolonged High Fat Diet Feeding

    PubMed Central

    Kim, Teayoun; Moore, John F; Sharer, Jon D; Yang, Kevin; Wood, Philip A; Yang, Qinglin

    2014-01-01

    Background Carnitine palmitoyltransferase 1 (CPT1) is the rate-limiting enzyme governing the entry of long-chain acyl-CoAs into mitochondria. Treatments with CPT1 inhibitors protect against insulin resistance in short-term preclinical animal studies. We recently reported that mice with muscle isoform CPT1b deficiency demonstrated improved insulin sensitivity when fed a High Fat-Diet (HFD) for up to 5 months. In this follow up study, we further investigated whether the insulin sensitizing effects of partial CPT1b deficiency could be maintained under a prolonged HFD feeding condition. Methods We investigated the effects of CPT1b deficiency on HFD-induced insulin resistance using heterozygous CPT1b deficient (Cpt1b+/−) mice compared with Wild Type (WT) mice fed a HFD for a prolonged period of time (7 months). We assessed insulin sensitivity using hyperinsulinemic-euglycemic clamps. We also examined body composition, skeletal muscle lipid profile, and changes in the insulin signaling pathways of skeletal muscle, liver, and adipose tissue. Results We found that Cpt1b+/− mice became severely insulin resistant after 7 months of HFD feeding. Cpt1b+/− mice exhibited a substantially reduced glucose infusion rate and skeletal muscle glucose uptake. While Cpt1b+/− mice maintained a slower weight gain with less fat mass than WT mice, accumulation of lipid intermediates became evident in the muscle of Cpt1b+/− but not WT mice after 7 months of HFD feeding. Insulin signaling was impaired in the Cpt1b+/− as compared to the WT muscles. Conclusion Partial CPT1b deficiency, mimicking CPT1b inhibition, may lead to impaired insulin signaling and insulin sensitivity under a prolonged HFD feeding condition. Therefore, further studies on the potential detrimental effects of prolonged therapy with CPT1 inhibition are necessary in the development of this potential therapeutic strategy. PMID:25580367

  4. Multiplex PCR assay specific for the multidrug-resistant strain W of Mycobacterium tuberculosis.

    PubMed

    Plikaytis, B B; Marden, J L; Crawford, J T; Woodley, C L; Butler, W R; Shinnick, T M

    1994-06-01

    In 1991, a multidrug-resistant strain of Mycobacterium tuberculosis was isolated from eight people with tuberculosis at a state correctional facility in New York. This strain, which is designated strain W (IS6110 restriction fragment length polymorphism type 212072), was resistant to isoniazid, rifampin, ethambutol, streptomycin, kanamycin, ethionamide, and rifabutin. Since that outbreak, the W strain has been associated with outbreaks in five hospitals in the New York City area and is a continuing public health problem in the area. To be able to identify this strain rapidly, we developed a multiplex PCR assay which targets a direct repeat of IS6110 with a 556-bp intervening sequence (NTF-1). The amplification generates two amplicons from strain W, which indicate the presence and orientation of the NTF-1 sequence between the direct repeat of IS6110, and a third amplicon, which serves as an internal PCR control. The assay was evaluated with 193 isolates of M. tuberculosis, and all 48 strain W isolates among those 193 isolates were correctly identified. PMID:7915723

  5. Activity and electrophoretic profiles of liver aldehyde dehydrogenases from mice of inbred strains with different alcohol preference.

    PubMed

    Yamazaki, H; Nishiguchi, K; Miyamoto, R; Ogita, Z I; Nakanishi, S

    1983-01-01

    1. The activity of low Km-aldehyde dehydrogenase (ALDH) in the liver mitochondrial fraction (MT-fraction) from male C57BL/6J strain mice (alcohol preferring) was significantly higher than that from DBA/2 mice (alcohol avoiding). The F1 hybrids (C57BL/6J X DBA/2) did not exhibit the intermediate activity to these two strains. 2. Strain differences in liver mitochondrial ALDH isozymes were observed by isoelectric focusing. C57BL/6J strain had two isozymes at pH 7.1 while DBA/2 had no band at this pH. F1 hybrid mice had similar two bands with lower density to those of C57BL/6J at pH 7.1. There was no difference in zymograms of the soluble fraction between C57BL/6J and DBA/2 strains. 3. The present results suggest that the difference in alcohol preference of mice may depend on some restricted ALDH isozymes with different pl or electric mobility rather than the enzymatic activity in the liver MT-fraction. PMID:6822317

  6. Geography and genealogy of the human host harbouring a distinctive drug-resistant strain of tuberculosis.

    PubMed

    Brassard, Paul; Henry, Kevin A; Schwartzman, Kevin; Jomphe, Michèle; Olson, Sherry H

    2008-05-01

    For a strain of Mycobacterium tuberculosis mono-resistant to pyrazinamide (PZA), we report the geographic distribution within Quebec of the 77 cases diagnosed during 1990-2000. Known as the Quebec mutation (or the pncA deletion), the strain is rare in urban areas and showed an unexpected concentration in Mauricie, one of the 16 health districts of the province, with a cluster of 10 cases situated in a rural area of 35-km radius. The cases occurred among people >50 (98%), of French Canadian origins (90%), and are understood to have arisen by reactivation. The rarity in Montreal and smaller cities is explained by the youthfulness of massive postwar migrations. To reach back into the history of settlement, we examined genealogies: 92,429 ancestral marriages for 32 of the 77 PZA-resistant isolates and 226,535 for a set of 85 controls with isolates of more diverse mycobacterial strains. Genealogical analysis showed no salient common ancestor for the cases, and kinship among them was no greater than observed in control samples from the same regions. But it identified an unsuspected geographical region as the site of ancestral concentrations prior to 1840, for both resistant strains and controls. The following scenario is proposed for the resistant strain: endemic in a specific geographical region by 1800, it dispersed with families moving into regions opened to settlement in the 1840s and 1850s, among them Mauricie, where dispersion was intensified by seasonal mobility of labour in logging, milling and marketing timber. In high-incidence areas, it is difficult to distinguish cases of reactivation from recent infections, but the low-incidence context allows us to observe a 200-year trajectory of a distinctive drug-resistant strain of M. tuberculosis. PMID:18316250

  7. High-Level Chromate Resistance in Arthrobacter sp. strain FB24 Requires Previously Uncharacterized Accessory Genes

    SciTech Connect

    Henne, Kristene L.; Nakatsu, Cindy N.; Thompson, Dorothea K.; Konopka, Allan

    2009-09-24

    The annotated genome sequence of Arthrobacter sp. strain FB24 revealed a chromate resistance determinant (CRD): a cluster of 8 genes located on a 10.6 kb fragment of a 96 kb plasmid. The CRD includes chrA, which encodes a putative chromate efflux protein, and three genes with amino acid similarities to the amino and carboxy termini of ChrB, a putative regulatory protein. There are also three novel genes that have not been previously associated with chromate resistance in other bacteria; they encode an oxidoreductase (most similar to malate:quinone oxidoreductase), a functionally unknown protein with a WD40 repeat domain and a lipoprotein. A chromate-sensitive mutant (strain D11) was generated by curing FB24 of its 96-kb plasmid. Elemental analysis indicated that chromate-exposed cells of strain D11 accumulated three times more chromium than strain FB24. Introduction of the CRD into strain D11 conferred chromate resistance comparable to wild-type levels, whereas deletion of specific regions of the CRD led to decreased resistance. Using real-time reverse transcriptase PCR, we show that expression of each gene within the CRD is specifically induced in response to chromate but not by lead, hydrogen peroxide or arsenate. Higher levels of chrA expression were achieved when the chrB orthologs and the WD40 repeat domain genes were present, suggesting their regulatory roles. Collectively, our findings indicate that chromate resistance in strain FB24 is primarily achieved by plasmid-mediated chromate efflux with the contribution of previously unrecognized accessory genes.

  8. Alkaline phosphatases and aminopeptidases are altered in a Cry11Aa resistant strain of Aedes aegypti

    PubMed Central

    Lee, Su-Bum; Aimanova, Karlygash G.; Gill, Sarjeet S.

    2014-01-01

    Bacillus thuringiensis subsp. israelensis (Bti) has been widely for the biological control of mosquito populations. However, the mechanism of Bti toxins is still not fully understood. To further elucidate the mechanism of Bti toxins, we developed an Aedes aegypti resistant strain that shows high-level resistance to Cry11Aa toxin. After 27 selections with Cry11Aa toxin, the larvae showed a 124-fold resistance ratio for Cry11Aa (strain G30). G30 larvae showed cross-resistance to Cry4Aa (66-fold resistance), less to Cry4Ba (13-fold), but not to Cry11Ba (2-fold). Midguts from these resistant larvae did not show detectable difference in the processing of the Cry11Aa toxin compared to that in susceptible larvae (WT). Brush border membrane vesicles (BBMV) from resistant larvae bound slightly less Cry11Aa compared to WT BBMV. To identify potential proteins associated with Cry11A resistance, not only transcript changes in the larval midgut were analyzed using Illumina sequencing and qPCR, but alterations of previously identified receptor proteins were investigated using immunoblots. The transcripts of 375 genes were significantly increased and those of 208 genes were down regulated in the resistant larvae midgut compared to the WT. None of the transcripts for previously identified receptors of Cry11Aa (Aedes cadherin, ALP1, APN1, and APN2) were altered in these analyses. The genes for the identified functional receptors in resistant larvae midgut did not contain any mutation in their sequences nor was there any change in their transcript expression levels compared to WT. However, ALP proteins were expressed at reduced levels (~40%) in the resistant strain BBMV. APN proteins and their activity were also slightly reduced in resistance strain. The transcript levels of ALPs (AAEL013330 and AAEL015070) and APNs (AAEL008158, AAEL008162) were significantly reduced. These results strongly suggest that ALPs and APNs could be associated with Cry11Aa resistance in Ae. aegypti. PMID

  9. Alkaline phosphatases and aminopeptidases are altered in a Cry11Aa resistant strain of Aedes aegypti.

    PubMed

    Lee, Su-Bum; Aimanova, Karlygash G; Gill, Sarjeet S

    2014-11-01

    Bacillus thuringiensis subsp. israelensis (Bti) is widely used for the biological control of mosquito populations. However, the mechanism of Bti toxins is still not fully understood. To further elucidate the mechanism of Bti toxins, we developed an Aedes aegypti resistant strain that shows high-level resistance to Cry11Aa toxin. After 27 selections with Cry11Aa toxin, the larvae showed a 124-fold resistance ratio for Cry11Aa (strain G30). G30 larvae showed cross-resistance to Cry4Aa (66-fold resistance), less to Cry4Ba (13-fold), but not to Cry11Ba (2-fold). Midguts from these resistant larvae did not show detectable difference in the processing of the Cry11Aa toxin compared to that in susceptible larvae (WT). Brush border membrane vesicles (BBMV) from resistant larvae bound slightly less Cry11Aa compared to WT BBMV. To identify potential proteins associated with Cry11A resistance, not only transcript changes in the larval midgut were analyzed using Illumina sequencing and qPCR, but alterations of previously identified receptor proteins were investigated using immunoblots. The transcripts of 375 genes were significantly increased and those of 208 genes were down regulated in the resistant larvae midgut compared to the WT. None of the transcripts for previously identified receptors of Cry11Aa (Aedes cadherin, ALP1, APN1, and APN2) were altered in these analyses. The genes for the identified functional receptors in resistant larvae midgut did not contain any mutation in their sequences nor was there any change in their transcript expression levels compared to WT. However, ALP proteins were expressed at reduced levels (∼ 40%) in the resistant strain BBMV. APN proteins and their activity were also slightly reduced in resistance strain. The transcript levels of ALPs (AAEL013330 and AAEL015070) and APNs (AAEL008158, AAEL008162) were significantly reduced. These results strongly suggest that ALPs and APNs could be associated with Cry11Aa resistance in Ae. aegypti. PMID

  10. Tetracycline and oxytetracycline resistance determinants detected in Bacillus cereus strains isolated from honey samples.

    PubMed

    López, A C; de Ortúzar, R V M; Alippi, A M

    2008-01-01

    The aim of this study was to investigate the presence of tetracycline and oxytetracycline resistance determinants in Bacillus cereus strains isolated from honey samples. Of a total of 77 isolates analyzed, 30 (39%) exhibited resistance to tetracyclines according to the results of a disk diffusion method. Resistant strains (n=30) were screened by PCR for the presence of the resistant determinants tetK, tetL, tetM, tetO, tetW, otrA and otrB and their MIC values for tetracycline, oxytetracycline and minocycline were assessed. According to the PCR results, 23 isolates (77%) presented at least one tetracycline or oxytetracycline resistance determinant. The tetK genotype was present in 10 isolates while the tetL, tetM, and otrA genotypes were present in 3, 2, and 5 isolates, respectively. In addition, 2 isolates of the tetK plus tetM genotype, 1 of the tetK plus tetL genotype, and 1 of the tetK plus otrA genotype were found. All isolates were tetW, tetO and otrB negatives. On the other hand, 7 isolates (23%) showed a tetracycline-resistant and/or minocycline-resistant phenotype (MIC) but did not carry any of the tet or otr determinants investigated in this study. This research has shown that B. cereus isolates from honey samples contain a variety of tetracycline and oxytetracycline resistance genes, including the tetK and tetL determinants which encode for efflux proteins, and tetM and otrA, which encode for ribosomal protection proteins. These findings indicate that strains isolated from honeys could represent a reservoir for tetracycline resistance genes. To our knowledge, this is the first report of tetracycline-resistant and oxytetracycline-resistant B. cereus strains carrying the tetK determinant, and also the first report of oxytetracycline-resistant and tetracycline-resistant Bacillus species carrying the otrA determinant. PMID:19213248

  11. The effects of age and carbon black on airway resistance in mice

    PubMed Central

    Bennett, Blake; Mitzner, Wayne; Tankersley, Clarke G.

    2016-01-01

    Rationale Ambient particulate matter (PM) is associated with acute exacerbations of airflow obstruction. Additionally, elderly individuals are more susceptible to increased functional morbidity following acute PM exposure. Hypothesis/Objective The purpose of the current study is to determine the aging effects of PM exposure on the responsiveness of airway smooth muscle in mice. We hypothesized that airway reactivity induced by methacholine (Mch) will increase with age in PM exposed mice. Methods Male C57BL/6 (B6) mice at 11, 39, 67, and 96 wks of age were exposed to either carbon black (CB concentration ~550 µg/m3) or room air (RA) for 3 hours on 3 consecutive days. One day after the last exposure, mice were anesthetized and airways resistance (Raw) was measured using forced oscillation at baseline and 1 minute after increasing half-log doses (0.1 to 30 mg/ml) of aerosolized Mch. Results Baseline Raw was significantly lesser in mice at 39, 67, and 96 wks compared with 11-wk old mice (p < 0.05). In RA exposed mice, an age-dependent decline in Mch-induced airway reactivity occurred in association with the highest Mch doses at ages 67 and 96 wks (p < 0.05). CB exposure caused a significant (p < 0.05) increase in Mch-induced Raw response in 67-wk old CB exposed mice compared with age-matched RA mice. Conclusion Our results show a progressive decrease in the Mch-induced Raw response with age in B6 mice. Overall, the effect of CB exposure resulted in significant increases in airway reactivity in middle-aged mice. PMID:23150990

  12. Pathogenicity of Helicobacter ganmani in Mice Susceptible and Resistant to Infection with H. hepaticus

    PubMed Central

    Alvarado, Cynthia G; Kocsis, Andrew G; Hart, Marcia L; Crim, Marcus J; Myles, Matthew H; Franklin, Craig L

    2015-01-01

    Helicobacter spp. are some of the most prevalent bacterial contaminants of laboratory mice. Although abundant data regarding the diseases associated with H. hepaticus infection are available, little is known about the pathogenicity of H. ganmani, which was first isolated in 2001 from the intestines of laboratory mice. The objective of this study was to evaluate the host response to H. ganmani colonization in H. hepaticus disease-resistant C57BL/6 and disease-susceptible A/J and IL10-deficient mice. Mice were inoculated with H. ganmani, H. hepaticus, or Brucella broth. Cecal lesion scores, cecal gene expression, and Helicobacter load were measured at 4 and 90 d after inoculation. At both time points, mice inoculated with H. ganmani had similar or significantly more copies of cecum-associated Helicobacter DNA than did mice inoculated with H. hepaticus. When compared with those of sham-inoculated control mice, cecal lesion scores at 4 and 90 d after inoculation were not significantly greater in H. ganmani-inoculated A/J, C57BL/6, or IL10-deficient mice. Analysis of cecal gene expression demonstrated that H. ganmani infection failed to cause significant elevations of IFNγ in A/J, C57BL/6, or IL10-deficient mice. However, in IL10-deficient mice, H. ganmani infection was associated with a significant increase in the expression of the proinflammatory cytokine IL12/23p40. Although H. ganmani infection in this study failed to induce the typhlitis that is the hallmark of H. hepaticus infection, infection with H. ganmani was associated with alterations in inflammatory cytokines in IL10-deficient mice. PMID:25730753

  13. Effect of streptomycin administration on colonization resistance to Salmonella typhimurium in mice.

    PubMed Central

    Que, J U; Hentges, D J

    1985-01-01

    The addition of 5 mg of streptomycin sulfate per ml to the drinking water of Swiss white mice resulted in a 100,000-fold reduction in the 50% implantation dose of streptomycin-resistant Salmonella typhimurium for the animals. When streptomycin-treated and untreated mice were challenged orogastrically with 10(3) viable S. typhimurium organisms, 100% of the treated and none of the untreated mice excreted the pathogen in their feces. Similarly, translocation of S. typhimurium from the intestinal tract to the liver, spleen, and mesentery occurred in 10 of 10 treated mice but in none of the untreated mice 7 days after challenge with 10(3) CFU. Studies of colonization dynamics showed that S. typhimurium was present at high population levels in the intestines of streptomycin-treated mice and in detectable levels in the liver, spleen, and mesentery within 72 h after challenge with 10(3), 10(5), or 10(8) organisms. In untreated mice challenged with either 10(3) or 10(5) S. typhimurium organisms, the organisms were isolated from ileal and cecal tissues but not from ileal or cecal contents or from extraintestinal tissue 72 h after challenge. When untreated mice were challenged with 10(8) organisms, however, S. typhimurium was present in all organs and in intestinal contents. Streptomycin treatment, therefore, facilitated colonization and development of streptomycin-resistant S. typhimurium populations in intestines of mice and the subsequent translocation of the organisms from the intestinal tract to other tissues. PMID:3884509

  14. Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice

    PubMed Central

    Steiner, Nadia; Carneiro, Lionel; Favrod, Céline; Preitner, Frédéric; Thorens, Bernard; Stehle, Jean-Christophe; Dix, Laure; Pralong, François; Magistretti, Pierre J.; Pellerin, Luc

    2013-01-01

    The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1+/− mice developed normally. However, when fed high fat diet (HFD), MCT1+/− mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1+/+ mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1+/− mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O2 consumption and CO2 production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1+/+ mice when fed HFD, were reduced in MCT1+/− mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1+/+ mice under high fat diet was prevented in the liver of MCT1+/− mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet. PMID:24367518

  15. Effects of Combination of Thiazolidinediones with Melatonin in Dexamethasone-induced Insulin Resistance in Mice

    PubMed Central

    Ghaisas, M. M.; Ahire, Y. S.; Dandawate, P. R.; Gandhi, S. P.; Mule, M.

    2011-01-01

    In type 2 Diabetes, oxidative stress plays an important role in development and aggregation of insulin resistance. In the present study, long term administration of the dexamethasone led to the development of insulin resistance in mice. The effect of thiazolidinediones pioglitazone and rosiglitazone, with melatonin on dexamethasone-induced insulin resistance was evaluated in mice. Insulin resistant mice were treated with combination of pioglitazone (10 mg/kg/day, p.o.) or rosiglitazone (5 mg/kg/day, p.o.) with melatonin 10 mg/kg/day p.o. from day 7 to day 22. In the biochemical parameters, the serum glucose, triglyceride levels were significantly lowered (P<0.05) in the combination groups as compared to dexamethasone treated group as well as with individual groups of pioglitazone, rosiglitazone, and melatonin. There was also, significant increased (P<0.05) in the body weight gain in combination treated groups as compared to dexamethasone as well as individual groups. The combination groups proved to be effective in normalizing the levels of superoxide dismutase, catalase, glutathione reductase and lipid peroxidation in liver homogenates may be due to antioxidant effects of melatonin and decreased hyperglycemia induced insulin resistance by thiazolidinediones. The glucose uptake in the isolated hemidiaphragm of mice was significantly increased in combination treated groups (PM and RM) than dexamethasone alone treated mice as well as individual (pioglitazone, rosiglitazone, melatonin) treated groups probably via increased in expression of GLUT-4 by melatonin and thiazolidinediones as well as increased in insulin sensitivity by thiazolidinediones. Hence, it can be concluded that combination of pioglitazone and rosiglitazone, thiazolidinediones, with melatonin may reduces the insulin resistance via decreased in oxidative stress and control on hyperglycemia. PMID:23112392

  16. Impaired acquired resistance of mice to Klebsiella pneumoniae infection induced by acute NO/sub 2/ exposure

    SciTech Connect

    Bouley, G.; Azoulay-Dupuis, E.; Gaudebout, C.

    1985-12-01

    The natural resistance of nonimmunized C57B1/6 mice to an intraperitoneal Klebsiella pneumoniae challenge was not significantly affected by prior continuous exposure to 20 ppm NO/sub 2/ for 4 days. In contrast, the acquired resistance of mice immunized just before and infected just after NO/sub 2/ exposure was seriously impaired. This could not be explained by the loss of appetite (about 30%) observed in NO/sub 2/ treated mice, for neither the natural nor acquired resistance of control air exposure mice given approximately 70% ad libitum food and water were significantly modified.

  17. Interaction between rifampicin, amodiaquine and artemether in mice infected with chloroquine resistant Plasmodium berghei

    PubMed Central

    2014-01-01

    Background Artemisinin-based combination therapy (ACT) remains the most effective chemotherapeutic strategy in the management of malaria. However, reports of reduced susceptibility of Plasmodium falciparum to the ACT justify the need for continued search for alternative anti-malarial drugs. The use of antibiotics with anti-malarial properties represents a potentially valuable chemotherapeutic option for the management of drug resistant infections. Thus, the intrinsic anti-malarial activity of the combination of clinical doses of rifampicin with amodiaquine and artemether was evaluated in an animal model using Plasmodium berghei. Methods A modification of the suppressive tests in vivo was employed. The anti-malarial activity of standard doses of amodiaquine (AQ) with or without artemether (ART) and combined with varying doses of rifampicin (RIF 15 mg/kg or RIF 30 mg/kg body weight) was evaluated in 40 mice sub-divided into eight groups and inoculated intraperitoneally with 1 × 107 red blood cells infected with chloroquine-resistant P. berghei ANKA strain. There were two control groups of animals, one group received amodiaquine alone while the other group received saline. Parasiticidal activity and survival of the animals were assessed over 21 days. Results Parasitaemia in the control animals peaked at 38% on day 9 and all animals died by day 10. The combination of amodiaquine with rifampicin 15 mg/kg body weight was the most effective of all the combinations and more efficacious than amodiaquine alone. The order of superiority of anti-malarial efficacy of the combinations was as follows; AQ + RIF 15 > AQ > AQ + ART + RIF 30 > AQ + ART + RIF 15 > AQ + RIF 30. Conclusion The combination of the clinical dose of rifampicin (15 mg/kg) with amodiaquine represents a potentially valuable treatment option in management of drug resistant malaria. In addition, the role of pharmacokinetic interaction in multiple drug therapy

  18. Inducible epithelial resistance protects mice against leukemia-associated pneumonia.

    PubMed

    Leiva-Juárez, Miguel M; Ware, Hayden H; Kulkarni, Vikram V; Zweidler-McKay, Patrick A; Tuvim, Michael J; Evans, Scott E

    2016-08-18

    Despite widespread infection prevention efforts, pneumonia remains the leading cause of death among patients with acute leukemia, due to complex disease- and treatment-dependent immune defects. We have reported that a single inhaled treatment with a synergistic combination of Toll-like receptor 2/6 (TLR 2/6) and TLR9 agonists (Pam2-ODN) induces protective mucosal defenses in mice against a broad range of pathogens. As Pam2-ODN-induced protection persists despite depletion of several leukocyte populations, we tested whether it could prevent pneumonia in a mouse model of acute myeloid leukemia (AML) remission induction therapy. Pam2-ODN prevented death due to pneumonia caused by Pseudomonas aeruginosa, Streptococcus pneumoniae, and Aspergillus fumigatus when mice were heavily engrafted with leukemia cells, had severe chemotherapy-induced neutropenia or both. Pam2-ODN also extended survival of pneumonia in NSG mice engrafted with primary human AML cells. Protection was associated with rapid pathogen killing in the lungs at the time of infection and with reduced pathogen burdens at distant sites at the end of observation. Pathogen killing was inducible directly from isolated lung epithelial cells and was not abrogated by the presence of leukemia cells or cytotoxic agents. Pam2-ODN had no discernible effect on replication rate, total tumor population, or killing by chemotherapy of mouse or human leukemia cells, either in vitro or in vivo. Taken together, we report that therapeutic stimulation of lung epithelial defenses robustly protects against otherwise lethal pneumonias despite the profound immune dysfunction associated with acute leukemia and its treatment. These findings may suggest an opportunity to protect this population during periods of peak vulnerability. PMID:27317793

  19. The effect of an acute bout of resistance exercise on carotid artery strain and strain rate.

    PubMed

    Black, Jane M; Stöhr, Eric J; Stone, Keeron; Pugh, Christopher J A; Stembridge, Mike; Shave, Rob; Esformes, Joseph I

    2016-09-01

    Arterial wall mechanics likely play an integral role in arterial responses to acute physiological stress. Therefore, this study aimed to determine the impact of low and moderate intensity double-leg press exercise on common carotid artery (CCA) wall mechanics using 2D vascular strain imaging. Short-axis CCA ultrasound images were collected in 15 healthy men (age: 21 ± 3 years; stature: 176.5 ± 6.2 cm; body mass; 80.6 ± 15.3 kg) before, during, and immediately after short-duration isometric double-leg press exercise at 30% and 60% of participants' one-repetition maximum (1RM: 317 ± 72 kg). Images were analyzed for peak circumferential strain (PCS), peak systolic and diastolic strain rate (S-SR and D-SR), and arterial diameter. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) were simultaneously assessed and arterial stiffness indices were calculated post hoc. A two-way repeated measures ANOVA revealed that during isometric contraction, PCS and S-SR decreased significantly (P < 0.01) before increasing significantly above resting levels post exercise (P < 0.05 and P < 0.01, respectively). Conversely, D-SR was unaltered throughout the protocol (P = 0.25). No significant differences were observed between the 30% and 60% 1RM trials. Multiple regression analysis highlighted that HR, BP, and arterial diameter did not fully explain the total variance in PCS, S-SR, and D-SR Acute double-leg press exercise is therefore associated with similar transient changes in CCA wall mechanics at low and moderate intensities. CCA wall mechanics likely provide additional insight into localized intrinsic vascular wall properties beyond current measures of arterial stiffness. PMID:27624687

  20. Inhibition of Carnitine Palmitoyltransferase-1 Activity Alleviates Insulin Resistance in Diet-Induced Obese Mice

    PubMed Central

    Keung, Wendy; Ussher, John R.; Jaswal, Jagdip S.; Raubenheimer, Monique; Lam, Victoria H.M.; Wagg, Cory S.; Lopaschuk, Gary D.

    2013-01-01

    Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated what effect inhibition of mitochondrial fatty acid uptake has on whole-body glucose tolerance and insulin sensitivity in obese insulin-resistant mice. C57BL/6 mice were fed a high-fat diet (60% calories from fat) for 12 weeks to develop insulin resistance. Subsequent treatment of mice for 4 weeks with the carnitine palmitoyltransferase-1 inhibitor, oxfenicine (150 mg/kg i.p. daily), resulted in improved whole-body glucose tolerance and insulin sensitivity. Exercise capacity was increased in oxfenicine-treated mice, which was accompanied by an increased respiratory exchange ratio. In the gastrocnemius muscle, oxfenicine increased pyruvate dehydrogenase activity, membrane GLUT4 content, and insulin-stimulated Akt phosphorylation. Intramyocellular levels of lipid intermediates, including ceramide, long-chain acyl CoA, and diacylglycerol, were also decreased. Our results demonstrate that inhibition of mitochondrial fatty acid uptake improves insulin sensitivity in diet-induced obese mice. This is associated with increased carbohydrate utilization and improved insulin signaling in the skeletal muscle, suggestive of an operating Randle Cycle in muscle. PMID:23139350

  1. Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice.

    PubMed

    Keung, Wendy; Ussher, John R; Jaswal, Jagdip S; Raubenheimer, Monique; Lam, Victoria H M; Wagg, Cory S; Lopaschuk, Gary D

    2013-03-01

    Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated what effect inhibition of mitochondrial fatty acid uptake has on whole-body glucose tolerance and insulin sensitivity in obese insulin-resistant mice. C57BL/6 mice were fed a high-fat diet (60% calories from fat) for 12 weeks to develop insulin resistance. Subsequent treatment of mice for 4 weeks with the carnitine palmitoyltransferase-1 inhibitor, oxfenicine (150 mg/kg i.p. daily), resulted in improved whole-body glucose tolerance and insulin sensitivity. Exercise capacity was increased in oxfenicine-treated mice, which was accompanied by an increased respiratory exchange ratio. In the gastrocnemius muscle, oxfenicine increased pyruvate dehydrogenase activity, membrane GLUT4 content, and insulin-stimulated Akt phosphorylation. Intramyocellular levels of lipid intermediates, including ceramide, long-chain acyl CoA, and diacylglycerol, were also decreased. Our results demonstrate that inhibition of mitochondrial fatty acid uptake improves insulin sensitivity in diet-induced obese mice. This is associated with increased carbohydrate utilization and improved insulin signaling in the skeletal muscle, suggestive of an operating Randle Cycle in muscle. PMID:23139350

  2. The Stimulation by Endotoxin of the Nonspecific Resistance of Mice to Bacterial Infections

    PubMed Central

    Hill, A. W.; Hibbitt, K. G.; Shears, A.

    1974-01-01

    The nonspecific resistance of mice to challenge was enhanced following the administration of an E. coli O55 B5 endotoxin. Although the route of administration of the endotoxin and the challenge organism were varied, the nonspecific resistance of the animal was enhanced in all the experiments. The efficiency of this resistance was highest when the inducing substance and the challenge dose of bacteria were administered intraperitoneally. Poly I: C and double stranded RNA were also studied but were much less effective than endotoxin in stimulating a resistance to infection. Stimulation of the fixed macrophages could not explain fully the enhanced resistance, since the clearance rates of colloidal carbon and radioactively labelled bacteria from the blood were not significantly enhanced after the administration of endotoxin. Furthermore, splenectomized animals, and animals injected with agents which interfere with the RES activity, trypan blue and corticosteroids, still developed a degree of nonspecific resistance to infection. PMID:4599349

  3. Murine cytomegalovirus stimulates natural killer cell function but kills genetically resistant mice treated with radioactive strontium.

    PubMed Central

    Masuda, A; Bennett, M

    1981-01-01

    Treatment of C3H/St mice with 100 microCi of 89Sr weakened their genetic resistance to murine cytomegalovirus (MCMV) infection. The criteria utilized to detect increased susceptibility were: (i) survival of mice; (ii) numbers of MCMV-infected cells in the spleens and liver; and (iii) serum glutamic pyruvic transaminase levels. The natural killer (NK) cell activity of spleen cells from mice treated with 89Sr is very low. However, the NK activities of spleen cells of both normal and 89Sr-treated mice were greatly augmented 3 days after infection with MCMV. These NK cells lysed a variety of tumor cells and shared several features with conventional NK cells, but were not lysed by anti-Nk-1.2 serum (specific for NK cells) plus complement. Splenic adherent cells did not lyse tumor cells themselves but were necessary for the stimulation of NK cells by MCMV. The paradox of high NK cell function and poor survival in 89Sr-treated mice infected with MCMV was a surprise. We conclude that these augmented NK cells, of themselves, cannot account for the genetic resistance of C3H/St mice to infection with MCMV. Images PMID:6277794

  4. Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry

    PubMed Central

    2011-01-01

    The macrolide class of antibiotics, including tylosin and tilmicosin, is widely used in the veterinary field for prophylaxis and treatment of mycoplasmosis. In vitro susceptibility testing of 50 strains of M. gallisepticum isolated in Israel during the period 1997-2010 revealed that acquired resistance to tylosin as well as to tilmicosin was present in 50% of them. Moreover, 72% (13/18) of the strains isolated from clinical samples since 2006 showed acquired resistance to enrofloxacin, tylosin and tilmicosin. Molecular typing of the field isolates, performed by gene-target sequencing (GTS), detected 13 molecular types (I-XIII). Type II was the predominant type prior to 2006 whereas type X, first detected in 2008, is currently prevalent. All ten type X strains were resistant to both fluoroquinolones and macrolides, suggesting selective pressure leading to clonal dissemination of resistance. However, this was not a unique event since resistant strains with other GTS molecular types were also found. Concurrently, the molecular basis for macrolide resistance in M. gallisepticum was identified. Our results revealed a clear-cut correlation between single point mutations A2058G or A2059G in domain V of the gene encoding 23S rRNA (rrnA, MGA_01) and acquired macrolide resistance in M. gallisepticum. Indeed, all isolates with MIC ≥ 0.63 μg/mL to tylosin and with MIC ≥ 1.25 μg/mL to tilmicosin possess one of these mutations, suggesting an essential role in decreased susceptibility of M. gallisepticum to 16-membered macrolides. PMID:21810258

  5. Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry.

    PubMed

    Gerchman, Irena; Levisohn, Sharon; Mikula, Inna; Manso-Silván, Lucía; Lysnyansky, Inna

    2011-01-01

    The macrolide class of antibiotics, including tylosin and tilmicosin, is widely used in the veterinary field for prophylaxis and treatment of mycoplasmosis. In vitro susceptibility testing of 50 strains of M. gallisepticum isolated in Israel during the period 1997-2010 revealed that acquired resistance to tylosin as well as to tilmicosin was present in 50% of them. Moreover, 72% (13/18) of the strains isolated from clinical samples since 2006 showed acquired resistance to enrofloxacin, tylosin and tilmicosin. Molecular typing of the field isolates, performed by gene-target sequencing (GTS), detected 13 molecular types (I-XIII). Type II was the predominant type prior to 2006 whereas type X, first detected in 2008, is currently prevalent. All ten type X strains were resistant to both fluoroquinolones and macrolides, suggesting selective pressure leading to clonal dissemination of resistance. However, this was not a unique event since resistant strains with other GTS molecular types were also found. Concurrently, the molecular basis for macrolide resistance in M. gallisepticum was identified. Our results revealed a clear-cut correlation between single point mutations A2058G or A2059G in domain V of the gene encoding 23S rRNA (rrnA, MGA_01) and acquired macrolide resistance in M. gallisepticum. Indeed, all isolates with MIC ≥ 0.63 μg/mL to tylosin and with MIC ≥ 1.25 μg/mL to tilmicosin possess one of these mutations, suggesting an essential role in decreased susceptibility of M. gallisepticum to 16-membered macrolides. PMID:21810258

  6. Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice

    NASA Technical Reports Server (NTRS)

    Hayes, N. L.; Nowakowski, R. S.

    2002-01-01

    The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'.

  7. Draft genome sequence of Acinetobacter baumannii strain NCTC 13423, a multidrug-resistant clinical isolate.

    PubMed

    Michiels, Joran E; Van den Bergh, Bram; Fauvart, Maarten; Michiels, Jan

    2016-01-01

    Acinetobacter baumannii is a pathogen that is becoming increasingly important and causes serious hospital-acquired infections. We sequenced the genome of A. baumannii NCTC 13423, a multidrug-resistant strain belonging to the international clone II group, isolated from a human infection in the United Kingdom in 2003. The 3,937,944 bp draft genome has a GC-content of 39.0 % and a total of 3672 predicted protein-coding sequences. The availability of genome sequences of multidrug-resistant A. baumannii isolates will fuel comparative genomic studies to help understand the worrying spread of multidrug resistance in this pathogen. PMID:27594976

  8. Antibiotic resistance profiles and virulence markers of Pseudomonas aeruginosa strains isolated from composts.

    PubMed

    Kaszab, Edit; Szoboszlay, Sándor; Dobolyi, Csaba; Háhn, Judit; Pék, Nikoletta; Kriszt, Balázs

    2011-01-01

    The aim of our work was to determine the presence of Pseudomonas aeruginosa in compost raw materials, immature and mature compost, and compost-treated soil. Twenty-five strains of P. aeruginosa were isolated from a raw material (plant straw), immature and mature compost and compost-treated soil samples. The strains were identified using the PCR method for the detection of species specific variable regions of 16S rDNA. Strains were examined for the presence of five different virulence-related gene sequences (exoA, exoU, exoT, exoS and exoY) and their antibiotic resistance profiles were determined. Based on our results, species P. aeruginosa can reach significant numbers (up to 10(6) MPN/g sample) during composting and 92.0% of the isolated strains carrying at least two gene sequences encoding toxic proteins. Various types of drug resistance were detected among compost originating strains, mainly against third generation Cephalosporins and Carbapenems. Six isolates were able to resist two different classes of antibiotics (third generation Cephalosporins and Carbapenems, wide spectrum Penicillins or Aminoglycosides, respectively). Based on our results, composts can be a source of P. aeruginosa and might be a concern to individuals susceptible to this opportunistic pathogen. PMID:20817443

  9. Relation between bacterial strain resistance to solvents and biodesulfurization activity in organic medium.

    PubMed

    Bouchez-Naïtali, Murielle; Abbad-Andaloussi, Samir; Warzywoda, Michel; Monot, Frédéric

    2004-09-01

    Microorganisms used in biodesulfurization of petroleum products have to withstand high concentrations of hydrocarbons. The capacities of seven desulfurizing strains of Rhodococcus to be active in the presence of solvents were evaluated. Octanol and toluene (log P=2.9) were selected as toxic solvents. The effect of the solvents was determined by measuring either inhibition of growth or the decrease in respiratory activity of the cells. Differences among strains in their resistance to solvent responses were observed, but these variations were dependent on the test used. Resistance to solvents was then compared to the capacity of the different strains to retain biodesulfurization activity in the presence of hexadecane. Inhibition of desulfurization by high concentrations of hexadecane was found to be well correlated to the sensitivity of the strains to respiration inhibition by toluene, but not to growth inhibition. This result also showed that the respirometric test was a rapid and reliable test to select solvent-resistant strains for use as resting cells in biocatalysis processes, such as biodesulfurization, in organic media. PMID:15133641

  10. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  11. Insulin resistance for glucose metabolism in disused soleus muscle of mice

    NASA Technical Reports Server (NTRS)

    Seider, M. J.; Nicholson, W. F.; Booth, F. W.

    1981-01-01

    Results of this study on mice provide the first direct evidence of insulin resistance for glucose metabolism in skeletal muscle that has undergone a previous period of reduced muscle usage. This lack of responsiveness to insulin developed in one day and in the presence of hypoinsulinemia. Future studies will utilize the model of hindlimb immobilization to determine the causes of these changes.

  12. Draft Genome Sequence of Three Antibiotic-Resistant Leuconostoc mesenteroides Strains of Dairy Origin

    PubMed Central

    Campedelli, Ilenia; Flórez, Ana Belén; Salvetti, Elisa; Delgado, Susana; Orrù, Luigi; Cattivelli, Luigi; Alegría, Ángel; Felis, Giovanna E.; Mayo, Baltasar

    2015-01-01

    Leuconostoc mesenteroides is a lactic acid bacterium (LAB) commonly associated with fermented foods. Here, we report the genome sequence of three selected dairy strains, showing atypical antibiotic resistances (AR). Genome analysis provided a better understanding of the genetic bases of AR in Leuconostoc and its potential transferability among foodborne bacteria. PMID:26358600

  13. Complete genome sequence of an attenuated Sparfloxacin-resistant Streptococcus agalactiae strain 138spar

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complete genome of a sparfloxacin-resistant Streptococcus agalactiae vaccine strain 138spar is 1,838,126 bp in size. The genome has 1892 coding sequences and 82 RNAs. The annotation of the genome is added by the NCBI Prokaryotic Genome Annotation Pipeline. The publishing of this genome will allo...

  14. Draft Genome Sequence of Three Antibiotic-Resistant Leuconostoc mesenteroides Strains of Dairy Origin.

    PubMed

    Campedelli, Ilenia; Flórez, Ana Belén; Salvetti, Elisa; Delgado, Susana; Orrù, Luigi; Cattivelli, Luigi; Alegría, Ángel; Felis, Giovanna E; Torriani, Sandra; Mayo, Baltasar

    2015-01-01

    Leuconostoc mesenteroides is a lactic acid bacterium (LAB) commonly associated with fermented foods. Here, we report the genome sequence of three selected dairy strains, showing atypical antibiotic resistances (AR). Genome analysis provided a better understanding of the genetic bases of AR in Leuconostoc and its potential transferability among foodborne bacteria. PMID:26358600

  15. Colistin Resistance mcr-1-Gene-Bearing Escherichia coli Strain from the United States.

    PubMed

    Meinersmann, Richard J; Ladely, Scott R; Plumblee, Jodie R; Hall, M Carolina; Simpson, Sheron A; Ballard, Linda L; Scheffler, Brian E; Genzlinger, Linda L; Cook, Kimberly L

    2016-01-01

    Transmissible colistin resistance in the form of an mcr-1-gene-bearing plasmid has been recently reported in Enterobacteriaceae in several parts of the world. We report here the completed genome sequence of an Escherichia coli strain isolated from swine in the United States that carried the mcr-1 gene on an IncI2-type plasmid. PMID:27587816

  16. Colistin Resistance mcr-1-Gene-Bearing Escherichia coli Strain from the United States

    PubMed Central

    Ladely, Scott R.; Plumblee, Jodie R.; Hall, M. Carolina; Simpson, Sheron A.; Ballard, Linda L.; Scheffler, Brian E.; Genzlinger, Linda L.; Cook, Kimberly L.

    2016-01-01

    Transmissible colistin resistance in the form of an mcr-1-gene-bearing plasmid has been recently reported in Enterobacteriaceae in several parts of the world. We report here the completed genome sequence of an Escherichia coli strain isolated from swine in the United States that carried the mcr-1 gene on an IncI2-type plasmid. PMID:27587816

  17. Draft Genome Sequence of a Metronidazole-Resistant Derivative of Gardnerella vaginalis Strain ATCC 14019

    PubMed Central

    Schuyler, Jessica A.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the genome sequence of a metronidazole-resistant derivative of Gardnerella vaginalis ATCC 14019. This strain was obtained after serial selection to increase the MIC from 4 to ≥500 µg/ml. Two coding changes, in genes encoding a response regulator and an NAD+ synthetase, arose during selection. PMID:26564054

  18. Evaluation of Verticillium Wilt Resistance in Russet Norkotah and Six Strain Selections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Strain selections of Russet Norkotah have been selected for enhanced vigor and high yield. In addition, they exhibit less severe expression of disease symptoms on the presence of Verticillium dahliae, a soil-borne fungal pathogen that causes Verticillium wilt. However, this apparent resistance may b...

  19. Sources of resistance to a new strain of Verticillium dahliae on sunflower in North America-2006

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2004, a new strain of Verticillium dahliae was identified in North Dakota and Minnesota and was designated NA-V2, which overcomes the V1 resistance gene in current sunflower hybrids. Greenhouse trials were conducted in 2004 and field trials were conducted in 2005 and 2006 to evaluate sunflower ge...

  20. Virulence genes, antibiotic resistance and integrons in Escherichia coli strains isolated from synanthropic birds from Spain.

    PubMed

    Sacristán, C; Esperón, F; Herrera-León, S; Iglesias, I; Neves, E; Nogal, V; Muñoz, M J; de la Torre, A

    2014-01-01

    The aim of this study was to determine the presence of virulence genes and antibiotic resistance profiles in 164 Escherichia coli strains isolated from birds (feral pigeons, hybrid ducks, house sparrows and spotless starlings) inhabiting urban and rural environments. A total of eight atypical enteropathogenic E. coli strains were identified: one in a house sparrow, four in feral pigeons and three in spotless starlings. Antibiotic resistance was present in 32.9% (54) of E. coli strains. The dominant type of resistance was to tetracycline (21.3%), ampicillin (19.5%) and sulfamethoxazole (18.9%). Five isolates had class 1 integrons containing gene cassettes encoding for dihydrofolate reductase A (dfrA) and aminoglycoside adenyltransferase A (aadA), one in a feral pigeon and four in spotless starlings. To our knowledge, the present study constitutes the first detection of virulence genes from E. coli in spotless starlings and house sparrows, and is also the first identification worldwide of integrons containing antibiotic resistance gene cassettes in E. coli strains from spotless starlings and pigeons. PMID:24689431

  1. Draft genome sequence of Inquilinus limosus strain MP06, a multidrug-resistant clinical isolate

    PubMed Central

    Pino, Marylú; Conza, José Di; Gutkind, Gabriel

    2015-01-01

    The bacterium, Inquilinus limosus, with its remarkable antimicrobial multiresistant profile, has increasingly been isolated in cystic fibrosis patients. We report draft genome sequence of a strain MP06, which is of considerable interest in elucidating the associated mechanisms of antibiotic resistance in this bacterium and for an insight about its persistence in airways of these patients. PMID:26691451

  2. Interaction of sugarbeet host resistance and Rhizoctonia solani AG-2-2 IIIB strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Rhizoctonia root rot caused by Rhizoctonia solani can cause serious economic losses in sugarbeet fields. Preliminary evidence suggests there could be interactions between different strains and resistance sources. Thus, field studies were conducted to determine if nine R. solani AG-2-2 IIIB str...

  3. Biochemical characterization of a multiple heavy metal, pesticides and phenol resistant Pseudomonas fluorescens strain.

    PubMed

    Wasi, Samina; Jeelani, Ghulam; Ahmad, Masood

    2008-04-01

    Pseudomonas fluorescens SM1 isolate was found to be resistant to some major water pollutants namely Cd2+, Cr6+, Cu2+, Ni2+, Pb2+, BHC, 2,4-D, mancozeb and phenols up to a concentration four times to the normal levels occurring in the highly pollulated regions. Curing experiment brought about the loss of one or more resistance markers indicating the plasmid born resistance. Plasmid profile of SM1 strain showed the presence of one DNA band of 43.6 kb. This Plasmid was isolated from SM1 strain and introduced into Escherichia coli DH5 alpha with a transformation frequency of 6.7 x 10(-4)transformants/recipient cell. The test SM1 strain was also capable of biotransforming Cr(VI) to Cr(III) which is less toxic compounds. Present studies further indicated that the test SM1 strain was not only resistant to 2,4-D, phenols and catechol but also capable of bioremediating these toxicants quite efficiently. Moreover, studies with inhibitors like sodium azide, 2,4-DNP and chloramphenicol suggested that the major mechanism for the bioremediation of the heavy metals other than Cr6+ would be the biosorption process. PMID:18164050

  4. Sarcocystis neurona infection in gamma interferon gene knockout (KO) mice: comparative infectivity of sporocysts in two strains of KO mice, effect of trypsin digestion on merozoite viability, and infectivity of bradyzoites to KO mice and cell culture.

    PubMed

    Dubey, J P; Sundar, N; Kwok, O C H; Saville, W J A

    2013-09-01

    The protozoan Sarcocystis neurona is the primary cause of Equine Protozoal Myeloencephalitis (EPM). EPM or EPM-like illness has been reported in horses, sea otters, and several other mammals. The gamma interferon gene knockout (KO) mouse is often used as a model to study biology and discovery of new therapies against S. neurona because it is difficult to induce clinical EPM in other hosts, including horses. In the present study, infectivity of three life cycle stages (merozoites, bradyzoites, sporozoites) to KO mice and cell culture was studied. Two strains of KO mice (C57-black, and BALB/c-derived, referred here as black or white) were inoculated orally graded doses of S. neurona sporocysts; 12 sporocysts were infective to both strains of mice and all infected mice died or became ill within 70 days post-inoculation. Although there was no difference in infectivity of sporocysts to the two strains of KO mice, the disease was more severe in black mice. S. neurona bradyzoites were not infectious to KO mice and cell culture. S. neurona merozoites survived 120 min incubation in 0.25% trypsin, indicating that trypsin digestion can be used to recover S. neurona from tissues of acutely infected animals. PMID:23375195

  5. [Alteration of Social Behaviors in Male Mice of CBA/Lac Strain under Agonistic Interactions].

    PubMed

    Kovalenko, I L; Kudryavtseva, N N

    2015-01-01

    Ability of people to communicate with each other is a necessary component of social behavior and normal development of individuals living in community. A pronounced impairment in communication may be the result of autism which is characterized by impaired socialization, low communication and restricted and/or repetitive behaviors. It is hypothesized that genes or rare mutations play a key role in the development of autism. However a multifold increase of the cases with autistic spectrum symptoms over the last years cannot be attributed exclusively to genetic mutations or heredity. Environmental contribution to the development of autistic symptoms has to be considered. The paper aimed to analyze the social behaviors of CBA/Lac mice with repeated experience of aggression or social defeats in daily agonistic interactions with accent on searches of associations with autistic symptoms in comparison with previously studied C57BL/6J animals. It has been shown that male mice of both strains with alternative social behaviors demonstrated the changes in social behaviors; however the expression of some form of behaviors was different. The data obtained to assert that long-term hostile social environment lead to development of disturbances in social behaviors, accompanying by autistic-like symptoms. PMID:26601507

  6. Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient Female Mice

    PubMed Central

    Huang, Chun-Fa; Yang, Ching-Yao; Chan, Ding-Cheng; Wang, Ching-Chia; Huang, Kuo-How; Wu, Chin-Ching; Tsai, Keh-Sung; Yang, Rong-Sen

    2015-01-01

    Background Epidemiological studies have reported that the prevalence of diabetes in women > 40 years of age, especially those in the postmenopausal phase, was higher than in men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear. Objectives We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. Methods Adult female mice who underwent ovariectomy or sham surgery were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2–6 weeks. Assays related to glucose metabolism were performed. Results Exposure of sham mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin intolerance, and insulin resistance were increased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was increased and liver glycogen content was decreased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Glucose-stimulated insulin secretion in islets isolated from arsenic-treated ovariectomized mice was also significantly decreased. Arsenic treatment significantly decreased plasma adiponectin levels in sham and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17β-estradiol supplementation. Conclusions Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females. Citation Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic

  7. [Evaluation of the efficacy of colistin/sulbactam combination on carbapenem-resistant Acinetobacter baumannii strains].

    PubMed

    Çetinkol, Yeliz; Telli, Murat; Altunçekiç Yıldırım, Arzu; Çalgın, Mustafa Kerem

    2016-07-01

    Acinetobacter baumannii strains, are opportunistic pathogens that cause severe nosocomial infections that are difficult to treat due to development of resistance to multiple antibiotics. As the antibiotic choices to be used in treatment are limited, combinations of a variety of antibiotics are used. The aims of this study were to identify the minimal inhibitory concentration (MIC) values of colistin and sulbactam against A.baumannii isolates and to determine the in vitro activity of colistin-sulbactam combination. A total of 50 A.baumannii strains isolated from different clinical specimens (32 tracheal aspirates, 10 blood, 6 urine and 2 wound samples) were included in the study. The identification of bacteria was performed by traditional methods and Vitek-2 (BioMerieux, France) automated system. Antibiotic susceptibilities were detected by Mueller-Hinton agar disk diffusion method and Vitek-2 automated system and the results were interpreted according to the CLSI standards. MIC values of colistin and sulbactam against A.baumannii strains and in vitro interactions of colistin-sulbactam combinations were determined with the E-test (BioMerieux, France). Fractional inhibitory concentration (FIC) index was used for the detection of efficacy of drug combinations. The presence of oxacillinase and metallo-beta-lactamase (MBL) genes that lead carbapenem resistance was investigated by polymerase chain reaction (PCR), and pulsed-field gel electrophoresis (PFGE) was performed for the determination of clonal relationship. In our study, all strains (100%) were detected as susceptible to colistin, 48 (96%) to trimethoprim/sulphamethoxazole and 18 to (36%) tigecyclin; however all of them were resistant to the other studied antibiotics, including sulbactam and carbapenem. When the colistin-sulbactam combination was assessed according to FIC index, all strains were found to have antagonistic effect. All of the carbapenem-resistant strains were positive for OXA-51 and OXA-23, and 3

  8. Three unsuccessful treatments of Helicobacter pylori infection by a highly virulent strain with quadruple antibiotic resistance.

    PubMed

    Boyanova, Lyudmila; Evstatiev, Ivailo; Yordanov, Daniel; Markovska, Rumyana; Mitov, Ivan

    2016-07-01

    We report a case of an adult patient undergoing three unsuccessful Helicobacter pylori treatments, including proton pump inhibitor (PPI), bismuth subcitrate, metronidazole and tetracycline in 2012, PPI, amoxicillin and clarithromycin in 2013, and PPI, amoxicillin and rifampin in 2014. Following the first treatment, the isolate was metronidazole and ciprofloxacin/levofloxacin resistant. After the second treatment, the isolate was resistant to metronidazole, ciprofloxacin/levofloxacin and rifampin, developing secondary clarithromycin resistance by A2143G mutation and was susceptible only to tetracycline. After the third treatment, the patient still remained H. pylori positive. Patient's strain was highly virulent (cagA (+) , cagE (+) and vacA s1a/m1/i1). The evolution of the patient's disease was from gastroesophageal reflux disease in 2012 to two duodenal ulcers in 2015. Briefly, the infecting strain showed quadruple antibiotic resistance and a transient amoxicillin resistance. Triple clarithromycin-based treatment induced secondary clarithromycin resistance by A2143G mutation, while rifampin resistance caused the third treatment failure. Several options for the next treatment regimens are discussed. PMID:26634607

  9. Paradoxical resistance to diet-induced obesity in UCP1-deficient mice

    PubMed Central

    Liu, Xiaotuan; Rossmeisl, Martin; McClaine, Jennifer; Kozak, Leslie P.

    2003-01-01

    The availability of mice lacking the mitochondrial uncoupling protein UCP1, has provided an opportunity to analyze the relationship between the capacity for energy expenditure and the development of obesity in response to a high-fat, high-sucrose diet. Congenic UCP1-deficient mice on a C57BL/6J genetic background show a temperature-dependent resistance to diet-induced obesity when compared with wild-type mice. This resistance, which occurs at 20°C, is quickly reversed when the ambient temperature is increased to 27°C. At 20°C, total oxygen consumption and physical activity of mutant and wild-type mice are indistinguishable; however, body temperature is higher in UCP1-deficient mice by 0.1–0.3°C, and respiratory quotient is slightly reduced. A reduced respiratory quotient, together with elevated β-hydroxybutyrate and reduced plasma fatty acid levels, suggests that the mutants oxidize a greater proportion of fat than wild-type mice, and that this possibly accounts for the resistance to diet-induced obesity. Although shivering is one alternative mechanism of thermogenesis that is probably used in UCP1-deficient mice, whether there are others remains to be determined. Nevertheless, our study underscores the paradox that elimination of the major thermogenic mechanism in the animal reduces rather than increases metabolic efficiency. We propose that in the absence of nonshivering thermogenesis, alternative, calorically more costly pathways of metabolism must be used to maintain body temperature. PMID:12569166

  10. Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice.

    PubMed

    Walji, Tezin A; Turecamo, Sarah E; Sanchez, Alejandro Coca; Anthony, Bryan A; Abou-Ezzi, Grazia; Scheller, Erica L; Link, Daniel C; Mecham, Robert P; Craft, Clarissa S

    2016-01-01

    Marrow adipose tissue (MAT) is an endocrine organ with the potential to influence skeletal remodeling and hematopoiesis. Pathologic MAT expansion has been studied in the context of severe metabolic challenge, including caloric restriction, high fat diet feeding, and leptin deficiency. However, the rapid change in peripheral fat and glucose metabolism associated with these models impedes our ability to examine which metabolic parameters precede or coincide with MAT expansion. Microfibril-associated glycoprotein-1 (MAGP1) is a matricellular protein that influences cellular processes by tethering signaling molecules to extracellular matrix structures. MAGP1-deficient (Mfap2 (-/-)) mice display a progressive excess adiposity phenotype, which precedes insulin resistance and occurs without changes in caloric intake or ambulation. Mfap2 (-/-) mice were, therefore, used as a model to associate parameters of metabolic disease, bone remodeling, and hematopoiesis with MAT expansion. Marrow adiposity was normal in Mfap2 (-/-) mice until 6 months of age; however, by 10 months, marrow fat volume had increased fivefold relative to wild-type control at the same age. Increased gonadal fat pad mass and hyperglycemia were detectable in Mfap2 (-/-) mice by 2 months, but peaked by 6 months. The development of insulin resistance coincided with MAT expansion. Longitudinal characterization of bone mass demonstrated a disconnection in MAT volume and bone volume. Specifically, Mfap2 (-/-) mice had reduced trabecular bone volume by 2 months, but this phenotype did not progress with age or MAT expansion. Interestingly, MAT expansion in the 10-month-old Mfap2 (-/-) mice was associated with modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis. Together, these findings indicate MAT expansion is coincident with insulin resistance, but not excess peripheral adiposity or hyperglycemia in Mfap2 (-/-) mice; and substantial MAT accumulation does

  11. Hepatocyte TRAF3 promotes insulin resistance and type 2 diabetes in mice with obesity

    PubMed Central

    Chen, Zheng; Canet, Mark J.; Sheng, Liang; Jiang, Lin; Xiong, Yi; Yin, Lei; Rui, Liangyou

    2015-01-01

    Objective Metabolic inflammation is believed to promote insulin resistance and type 2 diabetes progression in obesity. TRAF3, a cytoplasmic signaling protein, has been known to mediate/modulate cytokine signaling in immune cells. The goal is to define the metabolic function of hepatic TRAF3 in the setting of obesity. Methods Hepatocyte-specific TRAF3 knockout mice were generated using the loxp/albumin-cre system. Liver TRAF3 was deleted in adult obese mice via Cre adenoviral infection. Both high fat diet-induced and genetic obesity were examined. TRAF3 levels and insulin signaling were measured by immunoblotting. Insulin sensitivity, hepatic glucose production, and glucose metabolism were examined by glucose, insulin, and pyruvate tolerance tests. Hepatic steatosis was examined by Oil red O staining of liver sections and measuring liver triacylglycerol levels. Results Liver TRAF3 levels were lower in the fasted states in normal mice, and were aberrantly higher in obese mice and in mice with streptozotocin-induced hyperglycemia. Glucose directly increased TRAF3 levels in primary hepatocytes. Hepatocyte-specific deletion of TRAF3 decreased hyperinsulinemia, insulin resistance, glucose intolerance, and hepatic steatosis in mice with either high fat diet-induced obesity or genetic obesity (ob/ob); conversely, in lean mice, adenovirus-mediated overexpression of TRAF3 in the liver induced hyperinsulinemia, insulin resistance, and glucose intolerance. Deletion of TRAF3 enhanced the ability of insulin to stimulate phosphorylation of Akt in hepatocytes, whereas overexpression of TRAF3 suppressed insulin signaling. Conclusions Glucose increases the levels of hepatic TRAF3. TRAF3 in turn promotes hyperglycemia through increasing hepatic glucose production, thus forming a glucose-TRAF3 reinforcement loop in the liver. This positive feedback loop may drive the progression of type 2 diabetes and nonalcoholic fatty liver disease in obesity. PMID:26909311

  12. Anti-CD25 Treatment Depletes Treg Cells and Decreases Disease Severity in Susceptible and Resistant Mice Infected with Paracoccidioides brasiliensis

    PubMed Central

    Felonato, Maíra; Pina, Adriana; de Araujo, Eliseu Frank; Loures, Flávio V.; Bazan, Silvia B.; Feriotti, Cláudia; Calich, Vera L. G.

    2012-01-01

    Regulatory T (Treg) cells are fundamental in the control of immunity and excessive tissue pathology. In paracoccidioidomycosis, an endemic mycosis of Latin America, the immunoregulatory mechanisms that control the progressive and regressive forms of this infection are poorly known. Due to its modulatory activity on Treg cells, we investigated the effects of anti-CD25 treatment over the course of pulmonary infection in resistant (A/J) and susceptible (B10.A) mice infected with Paracoccidioides brasiliensis. We verified that the resistant A/J mice developed higher numbers and more potent Treg cells than susceptible B10.A mice. Compared to B10.A cells, the CD4+CD25+Foxp3+ Treg cells of A/J mice expressed higher levels of CD25, CTLA4, GITR, Foxp3, LAP and intracellular IL-10 and TGF-β. In both resistant and susceptible mice, anti-CD25 treatment decreased the CD4+CD25+Foxp3+ Treg cell number, impaired indoleamine 2,3-dioxygenase expression and resulted in decreased fungal loads in the lungs, liver and spleen. In A/J mice, anti-CD25 treatment led to an early increase in T cell immunity, demonstrated by the augmented influx of activated CD4+ and CD8+ T cells, macrophages and dendritic cells to the lungs. At a later phase, the mild infection was associated with decreased inflammatory reactions and increased Th1/Th2/Th17 cytokine production. In B10.A mice, anti-CD25 treatment did not alter the inflammatory reactions but increased the fungicidal mechanisms and late secretion of Th1/Th2/Th17 cytokines. Importantly, in both mouse strains, the early depletion of CD25+ cells resulted in less severe tissue pathology and abolished the enhanced mortality observed in susceptible mice. In conclusion, this study is the first to demonstrate that anti-CD25 treatment is beneficial to the progressive and regressive forms of paracoccidioidomycosis, potentially due to the anti-CD25-mediated reduction of Treg cells, as these cells have suppressive effects on the early T cell response in

  13. Differences in cadmium transport to the testis, epididymis, and brain in cadmium-sensitive and -resistant murine strains 129/J and A/J.

    PubMed

    King, L M; Banks, W A; George, W J

    1999-05-01

    Although most animals with scrotal testes are susceptible to cadmium-induced testicular toxicity, strain-related differences are seen in mice. Resistant murine strains demonstrate a decreased cadmium concentration in the testis and also in the epididymis and seminal vesicle. In this study we analyzed cadmium transport into tissues with a vascular barrier, the testis, epididymis, and brain, in an attempt to characterize the mechanisms of strain resistance to cadmium-induced testicular toxicity. In the resistant murine strain A/J, 109Cd transport (administered as 109CdCl2) was significantly attenuated in the testis, epididymis, and brain, when compared to the sensitive murine strain 129/J. The unidirectional influx constant (Ki, in microliter g-1 min-1) for 109Cd was 0.01929 in the A/J testis as compared with 1.174 in the 129/J testis (P <.0001). The percentage of a 109Cd dose that reached the A/J testis by 60 min was over 10 times less than that which reached the 129/J testis. The transport system used by cadmium in the 129/J testis was saturable, with 20 microM unlabeled cadmium chloride inhibiting transport by over 60%. The transporter was competitively inhibited by zinc (P =. 00017), but not by calcium, indicating a specificity in ion transport. Studies with isolated tubules and analysis of testicular fluid compartments demonstrated no significant difference in cadmium uptake or efflux between the strains when corrected for the amount of 109Cd entering the testis. Therefore, murine strain differences in testicular sensitivity to cadmium appear to be related to the variable presence of a transport system for cadmium in the testicular vasculature. PMID:10215659

  14. Intermediate Levels of Resistance to Tracheal Mites in Crosses Between Resistant and Susceptible Strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioassays and sampling of field colonies were used to test the hypothesis that the resistance to tracheal mites in Russian honey bees is a dominant trait. Earlier studies with Buckfast bees as a resistant parent had suggested dominance or partial dominance in their crosses with either a Canadian su...

  15. Resistance of canine methicillin-resistant Staphylococcus pseudintermedius strains to pradofloxacin.

    PubMed

    Kizerwetter-Świda, Magdalena; Chrobak-Chmiel, Dorota; Rzewuska, Magdalena; Binek, Marian

    2016-09-01

    We investigated in vitro activity of a novel veterinary fluoroquinolone, pradofloxacin, against methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolates and compared with other fluoroquinolones. A total of 38 MRSP isolates were subjected to agar disk diffusion tests for sensitivity to pradofloxacin, orbifloxacin, marbofloxacin, enrofloxacin, and ciprofloxacin. The minimal inhibitory concentration (MIC) values of pradofloxacin, ciprofloxacin, and enrofloxacin were determined. Mutations in the genes encoding DNA gyrase subunit A (GyrA) and topoisomerase IV (GrlA) proteins associated with fluoroquinolone resistance were studied by an analysis of partial sequences of the genes encoding these proteins. Two MRSP isolates were susceptible in disk diffusion and microdilution test to all fluoroquinolones tested, including pradofloxacin. Based on the results of the disk diffusion testing, 33 of 38 isolates showed resistance to pradofloxacin and 3 were intermediate, whereas, by pradofloxacin MIC testing, 35 isolates were classified as resistant and 1 as intermediate. Single alterations in GyrA and GrlA proteins were observed in the 35 resistant isolates and the 1 intermediate isolate (MIC results). These same 36 isolates were also resistant to the other tested fluoroquinolones. The results of the current study showed that MRSP isolates are usually resistant to all fluoroquinolones, including pradofloxacin. Therefore, in routine susceptibility testing to pradofloxacin by disk diffusion, the results should be carefully interpreted for MRSP isolates, especially those resistant to other fluoroquinolones and, in questionable cases, the pradofloxacin MIC should be determined to confirm the susceptibility testing results. PMID:27449131

  16. Phosphonoacetic Acid-Resistant Herpes Simplex Virus Infection in Hairless Mice1

    PubMed Central

    Klein, Richard J.; Friedman-Kien, Alvin E.

    1975-01-01

    Phosphonoacetic acid (PAA)-resistant type 1 herpes simplex virus population was isolated by repeated passage of the virus in the presence of this inhibitor. Hairless mice infected percutaneously with the inhibitor-resistant or the parental inhibitor-susceptible virus were treated intraperitoneally with PAA and 9-β-d-arabinofuranosyl-adenine by using several different dosage schedules. Whereas 9-β-d-arabinofuranosyl-adenine was effective both in the PAA-susceptible and PAA-resistant herpes simplex virus-induced skin infection, PAA suppressed only the infection induced by the parental PAA-susceptible virus. PMID:166611

  17. Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library.

    PubMed

    Kim, Si-Hyun; Park, Chulmin; Chun, Hye-Sun; Lee, Dong-Gun; Choi, Jae-Ki; Lee, Hyo-Jin; Cho, Sung-Yeon; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong

    2016-07-01

    With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim-sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim-sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim-sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials. PMID:26974861

  18. Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis

    PubMed Central

    Baldwin, Patrick R.; Reeves, Analise Z.; Powell, Kimberly R.; Napier, Ruth J.; Swimm, Alyson I.; Sun, Aiming; Giesler, Kyle; Bommarius, Bettina; Shinnick, Thomas M.; Snyder, James P.; Liotta, Dennis C.; Kalman, Daniel

    2016-01-01

    Tuberculosis (TB) is a major public health concern worldwide with over 2 billion people currently infected. The rise of strains of Mycobacterium tuberculosis (Mtb) that are resistant to some or all first and second line antibiotics, including multidrug-resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) strains, is of particular concern and new anti-TB drugs are urgently needed. Curcumin, a natural product used in traditional medicine in India, exhibits anti-microbial activity that includes Mtb, however it is relatively unstable and suffers from poor bioavailability. To improve activity and bioavailability, mono-carbonyl analogs of curcumin were synthesized and screened for their capacity to inhibit the growth of Mtb and the related Mycobacterium marinum (Mm). Using disk diffusion and liquid culture assays, we found several analogs that inhibit in vitro growth of Mm and Mtb, including rifampicin-resistant strains. Structure activity analysis of the analogs indicated that Michael acceptor properties are critical for inhibitory activity. However, no synergistic effects were evident between the monocarbonyl analogs and rifampicin on inhibiting growth. Together, these data provide a structural basis for the development of analogs of curcumin with pronounced anti-mycobacterial activity and provide a roadmap to develop additional structural analogs that exhibit more favorable interactions with other anti-TB drugs. PMID:25618016

  19. Pilot Screening to Determine Antimicrobial Synergies in a Multidrug-Resistant Bacterial Strain Library

    PubMed Central

    Kim, Si-Hyun; Park, Chulmin; Chun, Hye-Sun; Choi, Jae-Ki; Lee, Hyo-Jin; Cho, Sung-Yeon; Park, Sun Hee; Choi, Su-Mi; Choi, Jung-Hyun; Yoo, Jin-Hong

    2016-01-01

    With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and high-throughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim–sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim–sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim–sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials. PMID:26974861

  20. Towards a tolerance toolkit: Gene expression signatures enabling the emergence of resistant bacterial strains

    NASA Astrophysics Data System (ADS)

    Erickson, Keesha; Chatterjee, Anushree

    2014-03-01

    Microbial pathogens are able to rapidly acquire tolerance to chemical toxins. Developing next-generation antibiotics that impede the emergence of resistance will help avoid a world-wide health crisis. Conversely, the ability to induce rapid tolerance gains could lead to high-yielding strains for sustainable production of biofuels and commodity chemicals. Achieving these goals requires an understanding of the general mechanisms allowing microbes to become resistant to diverse toxins. We apply top-down and bottom-up methodologies to identify biological network changes leading to adaptation and tolerance. Using a top-down approach, we perform evolution experiments to isolate resistant strains, collect samples for transcriptomic and proteomic analysis, and use the omics data to inform mathematical gene regulatory models. Using a bottom-up approach, we build and test synthetic genetic devices that enable increased or decreased expression of selected genes. Unique patterns in gene expression are identified in cultures actively gaining resistance, especially in pathways known to be involved with stress response, efflux, and mutagenesis. Genes correlated with tolerance could potentially allow the design of resistance-free antibiotics or robust chemical production strains.

  1. Complement Evasion by Borrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation

    PubMed Central

    Alitalo, Antti; Meri, Taru; Rämö, Lasse; Jokiranta, T. Sakari; Heikkilä, Tero; Seppälä, Ilkka J. T.; Oksi, Jarmo; Viljanen, Matti; Meri, Seppo

    2001-01-01

    The most characteristic features of the Lyme disease pathogens, the Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii (n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) strains or control bacteria (Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation. PMID:11349031

  2. The effect of shearing strain-rate on the ultimate shearing resistance of clay

    NASA Technical Reports Server (NTRS)

    Cheng, R. Y. K.

    1975-01-01

    An approach for investigating the shearing resistance of cohesive soils subjected to a high rate of shearing strain is described. A fast step-loading torque apparatus was used to induce a state of pure shear in a hollow cylindrical soil specimen. The relationship between shearing resistance and rate of shear deformation was established for various soil densities expressed in terms of initial void ratio or water content. For rate of shearing deformation studies, the shearing resistance increases initially with shearing velocity, but subsequently reaches a terminal value as the shearing velocity increases. The terminal shearing resistance is also found to increase as the density of the soil increases. The results of this investigation are useful in the rheological study of clay. It is particularly important for mobility problems of soil runways, since the soil resistance is found to be sensitive to the rate of shearing.

  3. Therapeutic efficacy of BO-3482, a novel dithiocarbamate carbapenem, in mice infected with methicillin-resistant Staphylococcus aureus.

    PubMed Central

    Nagano, R; Shibata, K; Naito, T; Fuse, A; Asano, K; Hashizume, T; Nakagawa, S

    1997-01-01

    The in vivo activity of BO-3482, which has a dithiocarbamate chain at the C-2 position of 1beta-methyl-carbapenem, was compared with those of vancomycin and imipenem in murine models of septicemia and thigh infection with methicillin-resistant Staphylococcus aureus (MRSA). Because BO-3482 was more susceptible than imipenem to renal dehydropeptidase I in a kinetic study of hydrolysis by this renal enzyme, the therapeutic efficacy of BO-3482 was determined during coadministration with cilastatin. In the septicemia models, which involved two homogeneous MRSA strains and one heterogeneous MRSA strain, the 50% effective doses were, respectively, 4.80, 6.06, and 0.46 mg/kg of body weight for BO-3482; 5.56, 2.15, and 1.79 mg/kg for vancomycin; and >200, >200, and 15.9 mg/kg for imipenem. BO-3482 was also as effective as vancomycin in an MRSA septicemia model with mice with cyclophosphamide-induced immunosuppression. In the thigh infection model with a homogeneous MRSA strain, the bacterial counts in tissues treated with BO-3482-cilastatin were significantly reduced in a dose-dependent manner compared with the counts in those treated with vancomycin and imipenem-cilastatin (P < 0.001). These results indicate that BO-3482-cilastatin is as effective as vancomycin in murine systemic infections and is more bactericidal than vancomycin in local-tissue infections. The potent in vivo activity of BO-3482-cilastatin against such MRSA infections can be ascribed to the good in vitro anti-MRSA activity and improved pharmacokinetics in mice when BO-3482 is combined with cilastatin and to the bactericidal nature of the carbapenem. PMID:9333062

  4. Resistance to clarithromycin and genotypes in Helicobacter pylori strains isolated in Sicily.

    PubMed

    Fasciana, Teresa; Calà, Cinzia; Bonura, Celestino; Di Carlo, Enza; Matranga, Domenica; Scarpulla, Giuseppe; Manganaro, Michele; Camilleri, Salvatore; Giammanco, Anna

    2015-11-01

    The resistance of Helicobacter pylori strains to clarithromycin is increasing in several developed countries and their association with a genetic pattern circulation has been variously explained as related to different geographical areas. In this study we have reported: the prevalence of the resistance of H. pylori, isolated in Sicily, to clarithromycin; the principal point of mutation associated with this resistance; and the more frequent association between resistance to clarithromycin and cagA, the EPIYA motif, and the vacA and oipA genes. Resistance to clarithromycin was detected in 25% of cases, the main genetic mutation involved being A2143G. The cagA gene was present in 48% of cases and the distribution of the EPIYA motif was: ABC in 35 cases; ABCC in 8 cases; ABCCC in 2 cases; ABC-ABCC in 2 cases; and ABC-ABCC-ABCCC in 1 case. Regarding the vacA allele, an s1i1m1 combination was detected in 35% of cases, s1i1m2 in 12 %, s1i2m2 in 12%, s2i2m2 in 40%, and a double s1m1-m2 mosaic in 1% of cases. The status of the oipA gene was 'off' in 45% of cases and 'on' in 55%. Resistance to clarithromycin was found to be high in Sicily, but no correlation was found among resistance to clarithromycin, the vacA gene and oipA status; a higher correlation was observed between resistant strains and cagA-negative strains. PMID:26338221

  5. Comparative Genomic Analysis of Mycobacterium tuberculosis Drug Resistant Strains from Russia

    PubMed Central

    Ilina, Elena N.; Shitikov, Egor A.; Ikryannikova, Larisa N.; Alekseev, Dmitry G.; Kamashev, Dmitri E.; Malakhova, Maja V.; Parfenova, Tatjana V.; Afanas’ev, Maxim V.; Ischenko, Dmitry S.; Bazaleev, Nikolai A.; Smirnova, Tatjana G.; Larionova, Elena E.; Chernousova, Larisa N.; Beletsky, Alexey V.; Mardanov, Andrei V.; Ravin, Nikolai V.; Skryabin, Konstantin G.; Govorun, Vadim M.

    2013-01-01

    Tuberculosis caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (MTB) strains is a growing problem in many countries. The availability of the complete nucleotide sequences of several MTB genomes allows to use the comparative genomics as a tool to study the relationships of strains and differences in their evolutionary history including acquisition of drug-resistance. In our work, we sequenced three genomes of Russian MTB strains of different phenotypes – drug susceptible, MDR and XDR. Of them, MDR and XDR strains were collected in Tomsk (Siberia, Russia) during the local TB outbreak in 1998–1999 and belonged to rare KQ and KY families in accordance with IS6110 typing, which are considered endemic for Russia. Based on phylogenetic analysis, our isolates belonged to different genetic families, Beijing, Ural and LAM, which made the direct comparison of their genomes impossible. For this reason we performed their comparison in the broader context of all M. tuberculosis genomes available in GenBank. The list of unique individual non-synonymous SNPs for each sequenced isolate was formed by comparison with all SNPs detected within the same phylogenetic group. For further functional analysis, all proteins with unique SNPs were ascribed to 20 different functional classes based on Clusters of Orthologous Groups (COG). We have confirmed drug resistant status of our isolates that harbored almost all known drug-resistance associated mutations. Unique SNPs of an XDR isolate CTRI-4XDR, belonging to a Beijing family were compared in more detail with SNPs of additional 14 Russian XDR strains of the same family. Only type specific mutations in genes of repair, replication and recombination system (COG category L) were found common within this group. Probably the other unique SNPs discovered in CTRI-4XDR may have an important role in adaptation of this microorganism to its surrounding and in escape from antituberculosis drugs

  6. Identification and Functional Analysis of Genome Mutations in a Fluoride-Resistant Streptococcus mutans Strain

    PubMed Central

    Brandt, Bernd Willem; Zhu, Yuanfang; Li, Jiyao; van Loveren, Cor; Deng, Dong Mei

    2015-01-01

    It is known that fluoride-resistant microorganisms are different from fluoride-sensitive ones in growth, adherence and metabolic activity. It was hypothesized that these phenotypic differences were due to stable genotypic changes in the fluoride-resistant strains. However, until now, no studies have reported these genotypic changes. The aim of this study is to identify such changes in a fluoride-resistant Streptococcus mutans strain (C180-2FR) using whole-genome shotgun (WGS) sequencing and to examine the potential function of the identified mutations by comparing gene expression between the fluoride-sensitive (C180-2) and C180-2FR strains. We performed 50 bp paired-end Illumina shotgun sequencing for both strains. Through extensive bioinformatic analysis, we were able to identify 8 single nucleotide polymorphisms (SNPs) in the genome of C180-2FR, which were further confirmed by Sanger sequencing. Expression of the genes containing or in proximity to the SNPs in C180-2 and C180-2FR was then quantified by real-time PCR. A gene cluster containing genes coding for fluoride antiporters was up-regulated 10-fold in C180-2FR when compared to that in C180-2, independent of growth phase. Two SNPs are located in this gene cluster, one in its promoter region and the other in its protein-coding region. In addition, one gene, which codes for a putative glycerol uptake facilitator protein, was found to be down-regulated by 60% in C180-2FR at an early growth phase. The promoter region of this gene contained a SNP. No difference in expression was found for the other SNP-containing genes. In summary, using WGS sequencing, we were able to uncover genetic changes in the genome of a fluoride-resistant strain. These findings can provide new insights into the mechanism of microbial fluoride resistance. PMID:25856576

  7. Profile of Cytokines and Chemokines Triggered by Wild-Type Strains of Rabies Virus in Mice.

    PubMed

    Appolinário, Camila Michele; Allendorf, Susan Dora; Peres, Marina Gea; Ribeiro, Bruna Devidé; Fonseca, Clóvis R; Vicente, Acácia Ferreira; Antunes, João Marcelo A de Paula; Megid, Jane

    2016-02-01

    Rabies is a lethal infectious disease that causes 55,000 human deaths per year and is transmitted by various mammalian species, such as dogs and bats. The host immune response is essential for avoiding viral progression and promoting viral clearance. Cytokines and chemokines are crucial in the development of an immediate antiviral response; the rabies virus (RABV) attempts to evade this immune response. The virus's capacity for evasion is correlated with its pathogenicity and the host's inflammatory response, with highly pathogenic strains being the most efficient at hijacking the host's defense mechanisms and thereby decreasing inflammation. The purpose of this study was to evaluate the expression of a set of cytokine and chemokine genes that are related to the immune response in the brains of mice inoculated intramuscularly or intracerebrally with two wild-type strains of RABV, one from dog and the other from vampire bat. The results demonstrated that the gene expression profile is intrinsic to the specific rabies variant. The prompt production of cytokines and chemokines seems to be more important than their levels of expression for surviving a rabies infection. PMID:26711511

  8. Strain variation in the adaptation of C57Bl6 and BALBc mice to chronic hypobaric hypoxia.

    PubMed

    Cramer, Nathan P; Xu, Xiufen; Christensen, Christine; Bierman, Alexis; Tankersley, Clarke G; Galdzicki, Zygmunt

    2015-05-01

    The interplay of environmental and genetic factors may lead to a spectrum of physiological and behavioral outcomes. How environmental stress factors interact with the diverse mouse genomes is still poorly understood and elucidating the underlying interactions requires specific stress models that can target integrated physiological systems. Here, we employ behavioral tests and whole-body plethysmography to examine the effects of 12 weeks of simulated high altitude (HA) exposure on two inbred mouse strains, BALBc and C57Bl6. We find that HA induced- weight loss recovers at significantly different rates in these two strains. Even at 12 weeks, however, both strains fail to reach body weight levels of controls. Performance on two motor tasks, rotarod and treadmill, improve with HA exposure but more prominently in BALBc mice. Whole-body plethysmography outcomes indicate that compensation to chronic HA includes increased respiratory frequencies and tidal volumes in both strains. However, the effects on tidal volume are significantly greater in BALBc mice and showed a biphasic course. Whole- body metabolic rates are also increased in both strains with prolonged HA exposure, but were more pronounced in BALBc mice suggestive of less successful adaptation in this strain. These adaptations occur in the absence of gross pathological changes in all major organs. Together these results indicate that chronic HA exposure results in environmental stressors that impact the specific physiological responses of BALBc more than C57Bl6 mice. Thus, these strains provide a promising platform for investigating how genetic backgrounds can differentially reinforce the effects of long-lasting environmental stressors and their potential to interact with psychological stressors. PMID:25647362

  9. Mice deficient in Muc4 are resistant to experimental colitis and colitis-associated colorectal cancer.

    PubMed

    Das, S; Rachagani, S; Sheinin, Y; Smith, L M; Gurumurthy, C B; Roy, H K; Batra, S K

    2016-05-19

    MUC4, a large transmembrane mucin normally expressed in the small and large intestine, is differentially expressed during inflammatory and malignant conditions of the colon. However, the expression pattern and the role of MUC4 in colitis and colorectal cancer (CRC) are inconclusive. Therefore, the aim of this study was to understand the role of Muc4 during inflammatory and malignant conditions of the colon. Here, we generated Muc4(-/-) mice and addressed its role in colitis and colitis-associated CRC using dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS experimental models, respectively. Muc4(-/-) mice were viable, fertile with no apparent defects. Muc4(-/-) mice displayed increased resistance to DSS-induced colitis compared with wild-type (WT) littermates that was evaluated by survival rate, body weight loss, diarrhea and fecal blood score, and histological score. Reduced infiltration of inflammatory cells, that is, CD3(+) lymphocytes and F4/80(+) macrophages was observed in the inflamed mucosa along with reduction in the mRNA levels of inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α and anti-microbial genes Lysozyme M and SLPI in the colon of Muc4(-/-) mice compared with WT littermates. Compensatory upregulation of Muc2 and Muc3 mucins under basal and DSS treatment conditions partly explains the resistance observed in Muc4(-/-) mice. Accordingly, Muc4(-/-) mice exhibited significantly reduced tumor burden compared with WT mice assessed in a colitis-induced tumor model using AOM/DSS. An increased percentage of Ki67(+) nuclei was observed in the tumors from WT compared with Muc4(-/-) mice suggesting Muc4 to be critical in intestinal cell proliferation during tumorigenesis. Taken together, we conclusively demonstrate for the first time the role of Muc4 in driving intestinal inflammation and inflammation-associated tumorigenesis using a novel Muc4(-/-) mouse model. PMID:26364605

  10. Evaluation of Bacillus thuringiensis Pathogenicity for a Strain of the Tick, Rhipicephalus microplus, Resistant to Chemical Pesticides

    PubMed Central

    Fernández-Ruvalcaba, Manuel; Peña-Chora, Guadalupe; Romo-Martínez, Armando; Hernández-Velázquez, Víctor; de Parra, Alejandra Bravo; De La Rosa, Diego Pérez

    2010-01-01

    The pathogenicity of four native strains of Bacillus thuringiensis against Rhipicephalus (Boophilus) microplus (Canestrine) (Acari: Ixodidae) was evaluated. A R. microplus strain that is resistant to organophosphates, pyrethroids, and amidines, was used in this study. Adult R. microplus females were bioassayed using the immersion test of Drummond against 60 B. thuringiensis strains. Four strains, GP123, GP138, GP130, and GP140, were found to be toxic. For the immersion test, the total protein concentration for each bacterial strain was 1.25 mg/ml. Mortality, oviposition, and egg hatch were recorded. All of the bacterial strains had significant effects compared to the controls, but no significant differences were seen between the 4 strains. It is evident that these B. thuringiensis strains have a considerable detrimental effect on the R. microplus strain that is resistant to pesticides. PMID:21062139

  11. Resistance to Malaria by Enhanced Phagocytosis of Erythrocytes in LMP7-deficient Mice

    PubMed Central

    Duan, Xuefeng; Imai, Takashi; Chou, Bin; Tu, Liping; Himeno, Kunisuke; Suzue, Kazutomo; Hirai, Makoto; Taniguchi, Tomoyo; Okada, Hiroko; Shimokawa, Chikako; Hisaeda, Hajime

    2013-01-01

    General cellular functions of proteasomes occur through protein degradation, whereas the specific function of immunoproteasomes is the optimization of antigen processing associated with MHC class I. We and others previously reported that deficiency in subunits of immunoproteasomes impaired the activation of antigen-specific CD8+ T cells, resulting in higher susceptibility to tumor and infections. We demonstrated that CD8+ T cells contributed to protection against malaria parasites. In this study, we evaluated the role of immunoproteasomes in the course of infection with rodent malaria parasites. Unexpectedly, Plasmodium yoelii infection of mice deficient in LMP7, a catalytic subunit of immunoproteasomes, showed lower parasite growth in the early phase of infection and lower lethality compared with control mice. The protective characteristics of LMP7-deficient mice were not associated with enhanced immune responses, as the mutant mice showed comparable or diminished activation of innate and acquired immunity. The remarkable difference was observed in erythrocytes instead of immune responses. Parasitized red blood cells (pRBCs) purified from LMP7-deficient mice were more susceptible to phagocytosis by macrophages compared with those from wild-type mice. The susceptibility of pRBC to phagocytosis appeared to correlate with deformity of the membrane structures that were only observed after infection. Our results suggest that RBCs of LMP7-deficient mice were more likely to deform in response to infection with malaria parasites, presumably resulting in higher susceptibility to phagocytosis and in the partial resistance to malaria. PMID:23527234

  12. [Investigation of plasmid-mediated quinolone resistance in Escherichia coli strains].

    PubMed

    Aktepe, Orhan Cem; Aşık, Gülşah; Cetinkol, Yeliz; Biçmen, Meral; Gülay, Zeynep

    2012-01-01

    Quinolones are widely used antimicrobial agents, particularly for the treatment of infections caused by gram-negative bacilli such as E.coli. As a consequence, quinolone resistance has been increasing among this species in recent years. Bacterial resistance to quinolones usually results from mutations in the chromosomal genes which encode topoisomerases and also the expression of efflux pumps and loss of porines contributed to development of quinolone resistance. However, recent studies have shown that the spread and increase of quinolone resistance may be due to the transfer of plasmid-mediated genes. To date, three groups of plasmid-mediated quinolone resistance genes, namely qnr, aac(6')-Ib-cr, and qepA, have been described. The aim of this study was to investigate the presence of plasmid-mediated quinolone resistance genes in E.coli clinical isolates. A total of 112 quinolone-resistant E.coli strains isolated from different clinical specimens (84 urine, 16 blood, 10 wound, 2 bronchoalveolar lavage) of which 78 (69.6%) were extended-spectrum beta-lactamase (ESBL) positive, in Afyon Kocatepe University Hospital, Microbiology Laboratory were included in the study. In the isolates, qnrA, qnrB, qnrS, qnrC, qepA, and aac(6')-1b-cr plasmid genes were analysed by polymerase chain reaction (PCR). After aac(6')- 1b determinant was amplified by PCR, all aac(6')-1b positive amplicons were analyzed by digestion with BseGI restriction enzyme to identify aac(6')-1b-cr variant. It was found that, none of the strains horboured qnrA, qnrB, qnrS, qnrC and qepA genes, however, plasmid-mediated quinolone resistance gene aac(6')-1b-cr was found positive in 59.8% (67/112) of the strains. It was notable that 86.6% (58/67) of those isolates were ESBL producers. The rates of quinolone resistance among E.coli isolates infections were high in our region and an increasing trend has been observed in recent years. Our data indicated that the presence of plasmid- mediated resistance genes

  13. Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

    SciTech Connect

    Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.

    1987-11-01

    Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.

  14. Peroxynitrite mediates muscle insulin resistance in mice via nitration of IRbeta/IRS-1 and Akt

    SciTech Connect

    Zhou Jun; Huang Kaixun

    2009-11-15

    Accumulating evidence suggests that peroxynitrite (ONOO{sup -}) is involved in the pathogenesis of insulin resistance. In the current study, we investigated whether insulin resistance in vivo could be mediated by nitration of proteins involved in the early steps of the insulin signal transduction pathway. Exogenous peroxynitrite donated by 3-morpholinosydnonimine hydrochloride (SIN-1) induced in vivo nitration of the insulin receptor beta subunit (IRbeta), insulin receptor substrate (IRS)-1, and protein kinase B/Akt (Akt) in skeletal muscle of mice and dramatically reduced whole-body insulin sensitivity and muscle insulin signaling. Moreover, in high-fat diet (HFD)-fed insulin-resistant mice, we observed enhanced nitration of IRbeta and IRS-1 in skeletal muscle, in parallel with impaired whole-body insulin sensitivity and muscle insulin signaling. Reversal of nitration of these proteins by treatment with the peroxynitrite decomposition catalyst FeTPPS yielded an improvement in whole-body insulin sensitivity and muscle insulin signaling in HFD-fed mice. Taken together, these findings provide new mechanistic insights for the involvement of peroxynitrite in the development of insulin resistance and suggest that nitration of proteins involved in the early steps of insulin signal transduction is a novel molecular mechanism of HFD-induced muscle insulin resistance.

  15. Attenuation of a virulent Aeromonas hydrophila with novobiocin and pathogenic characterization of the novobiocin-resistant strain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novobiocin-resistant strain AH11NOVO was obtained from a virulent A. hydrophila strain AH11P through selection of resistance to novobiocin. AH11NOVO was found to be avirulent to channel catfish (Ictalurus punctatus) whereas AH11P was virulent. When AH11NOVO vaccinated channel catfish were challeng...

  16. Attenuation of a virulent Aeromonas hydrophila with novobiocin and pathogenic characterization of the novobiocin-resistant strain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novobiocin-resistant strain AH11NOVO was obtained from a virulent A. hydrophila strain AH11P through selection of resistance to novobiocin. AH11NOVO was found to be avirulent to channel catfish whereas AH11P was virulent. When AH11NOVO vaccinated channel catfish were challenged with AH11P at 14 da...

  17. COMPARISON OF THE LUNG ADENOMA RESPONSE IN STRAIN A/J MICE AFTER INTRAPERITONEAL AND ORAL ADMINISTRATION OF CARCINOGENS

    EPA Science Inventory

    This study was undertaken to compare the ability of a series of compounds from different chemical classes to induce lung tumors in strain A/J mice after either ip or po administration. 3-Methylcholanthrene, benzo(a)pyrene, urethan, diethylnitrosamine, ethylnitrosourea, and dimeth...

  18. Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice.

    PubMed

    Hortle, Elinor; Nijagal, Brunda; Bauer, Denis C; Jensen, Lora M; Ahn, Seong Beom; Cockburn, Ian A; Lampkin, Shelley; Tull, Dedreia; McConville, Malcolm J; McMorran, Brendan J; Foote, Simon J; Burgio, Gaetan

    2016-09-01

    The factors that determine red blood cell (RBC) lifespan and the rate of RBC aging have not been fully elucidated. In several genetic conditions, including sickle cell disease, thalassemia, and G6PD deficiency, erythrocyte lifespan is significantly shortened. Many of these diseases are also associated with protection from severe malaria, suggesting a role for accelerated RBC senescence and clearance in malaria resistance. Here, we report a novel, N-ethyl-N-nitrosourea-induced mutation that causes a gain of function in adenosine 5'-monophosphate deaminase (AMPD3). Mice carrying the mutation exhibit rapid RBC turnover, with increased erythropoiesis, dramatically shortened RBC lifespan, and signs of increased RBC senescence/eryptosis, suggesting a key role for AMPD3 in determining RBC half-life. Mice were also found to be resistant to infection with the rodent malaria Plasmodium chabaudi. We propose that resistance to P. chabaudi is mediated by increased RBC turnover and higher rates of erythropoiesis during infection. PMID:27465915

  19. Genetic analysis of antibiotic-resistance determinants in multidrug-resistant Shigella strains isolated from Chilean children.

    PubMed

    Toro, C S; Farfán, M; Contreras, I; Flores, O; Navarro, N; Mora, G C; Prado, V

    2005-02-01

    A total of 162 clinical isolates of Shigella collected from children in a semi-rural community of Chile were examined for the presence of genetic determinants of resistance to ampicillin, chloramphenicol, tetracycline, and trimethoprim. Ampicillin resistance was most frequently associated with the presence of bla(OXA) in S. flexneri and with bla(TEM) in S. sonnei. The bla(OXA) gene but not bla(TEM) was located in class 1 integrons. The dhfrIa gene encoding for resistance to trimethoprim was associated to class 2 integrons and detected exclusively in S. flexneri, whereas dhfrIIIc was found in all S. sonnei strains and in 10% of the S. flexneri isolates. Cat, coding for choramphenicol resistance, and bla(OXA) genes were located in the chromosome in all cases, whereas tetA gene, coding for tetracycline resistance, and bla(TEM), dhfrIa and dhfrIIIc genes were found either in the chromosome or in conjugative plasmids. Our results show a heterogenous distribution of antibiotic-resistance determinants between S. flexneri and S. sonnei. PMID:15724714

  20. Genetic analysis of antibiotic-resistance determinants in multidrug-resistant Shigella strains isolated from Chilean children.

    PubMed Central

    Toro, C. S.; Farfán, M.; Contreras, I.; Flores, O.; Navarro, N.; Mora, G. C.; Prado, V.

    2005-01-01

    A total of 162 clinical isolates of Shigella collected from children in a semi-rural community of Chile were examined for the presence of genetic determinants of resistance to ampicillin, chloramphenicol, tetracycline, and trimethoprim. Ampicillin resistance was most frequently associated with the presence of bla(OXA) in S. flexneri and with bla(TEM) in S. sonnei. The bla(OXA) gene but not bla(TEM) was located in class 1 integrons. The dhfrIa gene encoding for resistance to trimethoprim was associated to class 2 integrons and detected exclusively in S. flexneri, whereas dhfrIIIc was found in all S. sonnei strains and in 10% of the S. flexneri isolates. Cat, coding for choramphenicol resistance, and bla(OXA) genes were located in the chromosome in all cases, whereas tetA gene, coding for tetracycline resistance, and bla(TEM), dhfrIa and dhfrIIIc genes were found either in the chromosome or in conjugative plasmids. Our results show a heterogenous distribution of antibiotic-resistance determinants between S. flexneri and S. sonnei. PMID:15724714

  1. Mechanism of Enhanced Activity of Liposome-Entrapped Aminoglycosides against Resistant Strains of Pseudomonas aeruginosa

    PubMed Central

    Mugabe, Clement; Halwani, Majed; Azghani, Ali O.; Lafrenie, Robert M.; Omri, Abdelwahab

    2006-01-01

    Pseudomonas aeruginosa is inherently resistant to most conventional antibiotics. The mechanism of resistance of this bacterium is mainly associated with the low permeability of its outer membrane to these agents. We sought to assess the bactericidal efficacy of liposome-entrapped aminoglycosides against resistant clinical strains of P. aeruginosa and to define the mechanism of liposome-bacterium interactions. Aminoglycosides were incorporated into liposomes, and the bactericidal efficacies of both free and liposomal drugs were evaluated. To define the mechanism of liposome-bacterium interactions, transmission electron microscopy (TEM), flow cytometry, lipid mixing assay, and immunocytochemistry were employed. Encapsulation of aminoglycosides into liposomes significantly increased their antibacterial activity against the resistant strains used in this study (MICs of ≥32 versus ≤8 μg/ml). TEM observations showed that liposomes interact intimately with the outer membrane of P. aeruginosa, leading to the membrane deformation. The flow cytometry and lipid mixing assays confirmed liposome-bacterial membrane fusion, which increased as a function of incubation time. The maximum fusion rate was 54.3% ± 1.5% for an antibiotic-sensitive strain of P. aeruginosa and 57.8% ± 1.9% for a drug-resistant strain. The fusion between liposomes and P. aeruginosa significantly enhanced the antibiotics' penetration into the bacterial cells (3.2 ± 2.3 versus 24.2 ± 6.2 gold particles/bacterium, P ≤ 0.001). Our data suggest that liposome-entrapped antibiotics could successfully resolve infections caused by antibiotic-resistant P. aeruginosa through an enhanced mechanism of drug entry into the bacterial cells. PMID:16723560

  2. Mechanism of enhanced activity of liposome-entrapped aminoglycosides against resistant strains of Pseudomonas aeruginosa.

    PubMed

    Mugabe, Clement; Halwani, Majed; Azghani, Ali O; Lafrenie, Robert M; Omri, Abdelwahab

    2006-06-01

    Pseudomonas aeruginosa is inherently resistant to most conventional antibiotics. The mechanism of resistance of this bacterium is mainly associated with the low permeability of its outer membrane to these agents. We sought to assess the bactericidal efficacy of liposome-entrapped aminoglycosides against resistant clinical strains of P. aeruginosa and to define the mechanism of liposome-bacterium interactions. Aminoglycosides were incorporated into liposomes, and the bactericidal efficacies of both free and liposomal drugs were evaluated. To define the mechanism of liposome-bacterium interactions, transmission electron microscopy (TEM), flow cytometry, lipid mixing assay, and immunocytochemistry were employed. Encapsulation of aminoglycosides into liposomes significantly increased their antibacterial activity against the resistant strains used in this study (MICs of > or =32 versus < or =8 microg/ml). TEM observations showed that liposomes interact intimately with the outer membrane of P. aeruginosa, leading to the membrane deformation. The flow cytometry and lipid mixing assays confirmed liposome-bacterial membrane fusion, which increased as a function of incubation time. The maximum fusion rate was 54.3% +/- 1.5% for an antibiotic-sensitive strain of P. aeruginosa and 57.8% +/- 1.9% for a drug-resistant strain. The fusion between liposomes and P. aeruginosa significantly enhanced the antibiotics' penetration into the bacterial cells (3.2 +/- 2.3 versus 24.2 +/- 6.2 gold particles/bacterium, P < or = 0.001). Our data suggest that liposome-entrapped antibiotics could successfully resolve infections caused by antibiotic-resistant P. aeruginosa through an enhanced mechanism of drug entry into the bacterial cells. PMID:16723560

  3. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice.

    PubMed

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-07-29

    Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes. PMID:26923756

  4. Rapid vascular responses to anthrax lethal toxin in mice containing a segment of chromosome 11 from the CAST/Ei strain on a C57BL/6 genetic background.

    PubMed

    Weigel, Kelsey J; Rues, Laura; Doyle, Edward J; Buchheit, Cassandra L; Wood, John G; Gallagher, Ryan J; Kelly, Laura E; Radel, Jeffrey D; Bradley, Kenneth A; LeVine, Steven M

    2012-01-01

    Host allelic variation controls the response to B. anthracis and the disease course of anthrax. Mouse strains with macrophages that are responsive to anthrax lethal toxin (LT) show resistance to infection while mouse strains with LT non-responsive macrophages succumb more readily. B6.CAST.11M mice have a region of chromosome 11 from the CAST/Ei strain (a LT responsive strain) introgressed onto a LT non-responsive C57BL/6J genetic background. Previously, B6.CAST.11M mice were found to exhibit a rapid inflammatory reaction to LT termed the early response phenotype (ERP), and displayed greater resistance to B. anthracis infection compared to C57BL/6J mice. Several ERP features (e.g., bloat, hypothermia, labored breathing, dilated pinnae vessels) suggested vascular involvement. To test this, Evan's blue was used to assess vessel leakage and intravital microscopy was used to monitor microvascular blood flow. Increased vascular leakage was observed in lungs of B6.CAST.11M mice compared to C57BL/6J mice 1 hour after systemic administration of LT. Capillary blood flow was reduced in the small intestine mesentery without concomitant leukocyte emigration following systemic or topical application of LT, the latter suggesting a localized tissue mechanism in this response. Since LT activates the Nlrp1b inflammasome in B6.CAST.11M mice, the roles of inflammasome products, IL-1β and IL-18, were examined. Topical application to the mesentery of IL-1β but not IL-18 revealed pronounced slowing of blood flow in B6.CAST.11M mice that was not present in C57BL/6J mice. A neutralizing anti-IL-1β antibody suppressed the slowing of blood flow induced by LT, indicating a role for IL-1β in the response. Besides allelic differences controlling Nlrp1b inflammasome activation by LT observed previously, evidence presented here suggests that an additional genetic determinant(s) could regulate the vascular response to IL-1β. These results demonstrate that vessel leakage and alterations to

  5. Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium perfringens Strains

    PubMed Central

    Park, Miseon

    2014-01-01

    Fluoroquinolone resistance affects toxin production of Clostridium perfringens strains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria. PMID:25587280

  6. Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium perfringens Strains.

    PubMed

    Park, Miseon; Rafii, Fatemeh

    2014-01-01

    Fluoroquinolone resistance affects toxin production of Clostridium perfringens strains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria. PMID:25587280

  7. The effect of oxytetracycline on insulin resistance in obese mice

    PubMed Central

    Bégin-Heick, Nicole; Bourassa, Michel; Heick, H. M. C.

    1974-01-01

    1. Chronic oxytetracycline treatment was found to improve the insulin resistance of the obese–hyperglycaemic mouse. 2. The improved response to insulin was accompanied by decreased concentrations of circulating insulin and glucose, by a decrease in the lipid content of the liver and by an increase in the insulin-receptor sites of the liver and adipose tissue. 3. The increase in insulin-receptor sites preceded the fall in blood glucose. 4. Comparable studies done on food-restricted animals indicated that although chronic food restriction corrected the hyperinsulinaemia it did not restore the insulin-receptor sites or the hyperglycaemia. PMID:4464837

  8. Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice.

    PubMed

    Massé, Ian O; Guillemette, Sonia; Laramée, Marie-Eve; Bronchti, Gilles; Boire, Denis

    2014-11-01

    Anophthalmia is a condition in which the eye does not develop from the early embryonic period. Early blindness induces cross-modal plastic modifications in the brain such as auditory and haptic activations of the visual cortex and also leads to a greater solicitation of the somatosensory and auditory cortices. The visual cortex is activated by auditory stimuli in anophthalmic mice and activity is known to alter the growth pattern of the cerebral cortex. The size of the primary visual, auditory and somatosensory cortices and of the corresponding specific sensory thalamic nuclei were measured in intact and enucleated C57Bl/6J mice and in ZRDCT anophthalmic mice (ZRDCT/An) to evaluate the contribution of cross-modal activity on the growth of the cerebral cortex. In addition, the size of these structures were compared in intact, enucleated and anophthalmic fourth generation backcrossed hybrid C57Bl/6J×ZRDCT/An mice to parse out the effects of mouse strains and of the different visual deprivations. The visual cortex was smaller in the anophthalmic ZRDCT/An than in the intact and enucleated C57Bl/6J mice. Also the auditory cortex was larger and the somatosensory cortex smaller in the ZRDCT/An than in the intact and enucleated C57Bl/6J mice. The size differences of sensory cortices between the enucleated and anophthalmic mice were no longer present in the hybrid mice, showing specific genetic differences between C57Bl/6J and ZRDCT mice. The post natal size increase of the visual cortex was less in the enucleated than in the anophthalmic and intact hybrid mice. This suggests differences in the activity of the visual cortex between enucleated and anophthalmic mice and that early in-utero spontaneous neural activity in the visual system contributes to the shaping of functional properties of cortical networks. PMID:25242615

  9. Variability in the cadherin gene in an Ostrinia nubilalis strain selected for Cry1Ab resistance.

    PubMed

    Bel, Yolanda; Siqueira, Herbert A A; Siegfried, Blair D; Ferré, Juan; Escriche, Baltasar

    2009-03-01

    Transgenic corn expressing Cry1Ab (a Bacillus thuringiensis toxin) is highly effective in the control of Ostrinia nubilalis. For its toxic action, Cry1Ab has to bind to specific insect midgut proteins. To date, in three Lepidoptera species resistance to a Cry1A toxin has been conferred by mutations in cadherin, a protein of the Lepidoptera midgut membrane. The implication of cadherin in the resistance of an Ostrinia nubilalis colony (Europe-R) selected with Bacillus thuringiensis Cry1Ab protoxin was investigated. Several major mutations in the cadherin (cdh) gene were found, which introduced premature termination codons and/or large deletions (ranging from 1383 to 1701bp). The contribution of these major mutations to the resistance was analyzed in resistant individuals that survived exposure to a high concentration of Cry1Ab protoxin. The results indicated that the presence of major mutations was drastically reduced in individuals that survived exposure. Previous inheritance experiments with the Europe-R strain indicated the involvement of more than one genetic locus and reduced amounts of the cadherin receptor. The results of the present work support a polygenic inheritance of resistance in the Europe-R strain, in which mutations in the cdh gene would contribute to resistance by means of an additive effect. PMID:19114103

  10. Hypertension and abnormal fat distribution but not insulin resistance in mice with P465L PPARγ

    PubMed Central

    Tsai, Yau-Sheng; Kim, Hyo-Jeong; Takahashi, Nobuyuki; Kim, Hyung-Suk; Hagaman, John R.; Kim, Jason K.; Maeda, Nobuyo

    2004-01-01

    Peroxisome proliferator–activated receptor γ (PPARγ), the molecular target of a class of insulin sensitizers, regulates adipocyte differentiation and lipid metabolism. A dominant negative P467L mutation in the ligand-binding domain of PPARγ in humans is associated with severe insulin resistance and hypertension. Homozygous mice with the equivalent P465L mutation die in utero. Heterozygous mice grow normally and have normal total adipose tissue weight. However, they have reduced interscapular brown adipose tissue and intra-abdominal fat mass, and increased extra-abdominal subcutaneous fat, compared with wild-type mice. They have normal plasma glucose levels and insulin sensitivity, and increased glucose tolerance. However, during high-fat feeding, their plasma insulin levels are mildly elevated in association with a significant increase in pancreatic islet mass. They are hypertensive, and expression of the angiotensinogen gene is increased in their subcutaneous adipose tissues. The effects of P465L on blood pressure, fat distribution, and insulin sensitivity are the same in both male and female mice regardless of diet and age. Thus the P465L mutation alone is sufficient to cause abnormal fat distribution and hypertension but not insulin resistance in mice. These results provide genetic evidence for a critical role for PPARγ in blood pressure regulation that is not dependent on altered insulin sensitivity. PMID:15254591

  11. Analysis of Spleen Cells in Susceptible and Resistant Mice with Experimental Lagochilascariosis

    PubMed Central

    Lara, Priscila Guirão; Prudente, Mariana Felix de Souza; Dias, Neusa Mariana Costa; Tambourgi, Denise Vilarinho; Lino-Junior, Ruy de Souza; Spadafora-Ferreira, Mônica; Carvalhaes, Mara Silvia

    2013-01-01

    Lagochilascariosis is an emerging parasitic disease caused by the helminth Lagochilascaris minor. The experimental mouse model has been used to study the immune response against L. minor infection. In the present work, immunohistochemistry analysis of spleen cells populations was evaluated in susceptible (C57BL/6) and resistant (BALB/c) mice experimentally infected with L. minor. The BALB/c mice exhibited increased spleen cell indexes as follows: F4/80+ at 100 days after infection (DPI), CD4+ at 100 and 250 DPI, CD8+ at 35 and 100 DPI, and CD19+ at 100, 150, and 250 DPI. In the spleens of the infected C57BL/6 mice, increased indexes of the following spleen cells were observed: F4/80+ cells at 250 DPI, CD4+ cells at 150 DPI, CD8+ cells at 35, 150, and 250 DPI, and CD19+ cells at 150 to 250 DPI. The index of spleen cells confirmed the differences between the control and infected groups at several time points following the infection. These data demonstrate an association between a preferential increase in the number of CD4+ and CD19+ spleen cells and resistance to experimental lagochilascariosis in BALB/c mice and between a preferential increase in the number of CD8+ spleen cells and susceptibility in C57BL/6 mice. PMID:27335846

  12. Flight take-off and walking behavior of insecticide-susceptible and - resistant strains of Sitophilus zeamais exposed to deltamethrin.

    PubMed

    Guedes, N M P; Guedes, R N C; Ferreira, G H; Silva, L B

    2009-08-01

    Insects have evolved a variety of physiological and behavioral responses to various toxins in natural and managed ecosystems. However, insect behavior is seldom considered in insecticide studies although insects are capable of changing their behavior in response to their sensory perception of insecticides, which may compromise insecticide efficacy. This is particularly serious for insect pests that are physiologically resistant to insecticides since insecticide avoidance may further compromise their management. Locomotion plays a major role determining insecticide exposure and was, therefore, considered in investigating the behavioral responses of male and female adult insects from an insecticide-susceptible and two insecticide-resistant strains of the maize weevil Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), a major pest of stored cereals. Different dose-dependent behavioral responses were expected among strains with behavioral resistance less likely to occur in physiologically resistant insects since they are able to withstand higher doses of insecticide. The behavioral responses to deltamethrin-sprayed surfaces differed among the maize weevil strains. Such responses were concentration-independent for all of the strains. Stimulus-independent behavioral resistance was unrelated to physiological resistance with one resistant strain exhibiting higher rates of flight take-off and the other resistant strain exhibiting lower flight take-off. Female mobility was similar for all strains, unlike male mobility. Males of each strain exhibited a pattern of mobility following the same trend of flight take-off. Behavioral patterns of response to insecticide are, therefore, variable among strains, particularly among insecticide-resistant strains, and worth considering in resistance surveys and management programs. PMID:19302721

  13. Metabolomics Analysis Identifies Intestinal Microbiota-Derived Biomarkers of Colonization Resistance in Clindamycin-Treated Mice

    PubMed Central

    Jump, Robin L. P.; Polinkovsky, Alex; Hurless, Kelly; Sitzlar, Brett; Eckart, Kevin; Tomas, Myreen; Deshpande, Abhishek; Nerandzic, Michelle M.; Donskey, Curtis J.

    2014-01-01

    Background The intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment. Methods To assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of antibiotic-treated mice, stool samples were analyzed using quantitative real-time polymerase chain reaction to assess changes in the microbiota and using non-targeted metabolic profiling. To assess whether the findings were applicable to another antibiotic class that suppresses intestinal anaerobes, similar experiments were conducted with piperacillin/tazobactam. Results Colonization resistance began to recover within 5 days and was intact by 12 days after clindamycin treatment, coinciding with the recovery bacteria from the families Lachnospiraceae and Ruminococcaceae, both part of the phylum Firmicutes. Clindamycin treatment caused marked changes in metabolites present in fecal specimens. Of 484 compounds analyzed, 146 (30%) exhibited a significant increase or decrease in concentration during clindamycin treatment followed by recovery to baseline that coincided with restoration of in vivo colonization resistance. Identified as potential biomarkers of colonization resistance, these compounds included intermediates in carbohydrate or protein metabolism that increased (pentitols, gamma-glutamyl amino acids and inositol metabolites) or decreased (pentoses, dipeptides) with clindamycin treatment. Piperacillin

  14. Synergistic Effects and Antibiofilm Properties of Chimeric Peptides against Multidrug-Resistant Acinetobacter baumannii Strains

    PubMed Central

    Gopal, Ramamourthy; Kim, Young Gwon; Lee, Jun Ho; Lee, Seog Ki; Chae, Jeong Don; Son, Byoung Kwan; Seo, Chang Ho

    2014-01-01

    The increasing prevalence of drug-resistant pathogens highlights the need to identify novel antibiotics. Here we investigated the efficacies of four new antimicrobial peptides (AMPs) for potential drug development. The antibacterial activities, synergistic effects, and antibiofilm properties of the four chimeric AMPs were tested against Acinetobacter baumannii, an emerging Gram-negative, nosocomial, drug-resistant pathogen. Nineteen A. baumannii strains resistant to ampicillin, cefotaxime, ciprofloxacin, tobramycin, and erythromycin were isolated at a hospital from patients with cholelithiasis. All four peptides exhibited significant antibacterial effects (MIC = 3.12 to 12.5 μM) against all 19 strains, whereas five commercial antibiotics showed little or no activity against the same pathogens. An exception was polymyxin, which was effective against all of the strains tested. Each of the peptides showed synergy against one or more strains when administered in combination with cefotaxime, ciprofloxacin, or erythromycin. The peptides also exhibited an ability to prevent biofilm formation, which was not seen with cefotaxime, ciprofloxacin, or erythromycin, though polymyxin also inhibited biofilm formation. Indeed, when administered in combination with ciprofloxacin, the AMP HPMA exerted a potent synergistic effect against A. baumannii biofilm formation. Collectively, our findings indicate that the AMPs tested have no cytotoxicity but possess potent antibacterial and antibiofilm activities and may act synergistically with commercial antibiotics. PMID:24366740

  15. Fungicide resistance and genetic variability in plant pathogenic strains of Guignardia citricarpa

    PubMed Central

    Possiede, Y.M.; Gabardo, J.; Kava-Cordeiro, V.; Galli-Terasawa, L.V.; Azevedo, J.L.; Glienke, C.

    2009-01-01

    Citrus black spot (CBS) is a plant disease of worldwide occurrence, affecting crops in Africa, Oceania, and South America. In Brazil, climate provides favorable conditions and CBS has spread to the Southeast and South regions. CBS is caused by the fungus Guignardia citricarpa (anamorph: Phyllosticta citricarpa) and its control is based on the use of fungicides, such as benzimidazoles. In South Africa, the disease was kept under control for 10 years with benomyl, until cases of resistance to high concentrations of this fungicide were reported from all citrus-producing areas. Azoxystrobin (a strobilurin) has been found effective in controlling phytopathogens, including CBS, in a wide range of economically important crops. The present study investigated in vitro the effects of the fungicides benomyl and azoxystrobin on 10 strains of G. citricarpa isolated from lesions in citrus plants from Brazil and South Africa. Benomyl at 0.5 μg/mL inhibited mycelial growth in all strains except PC3C, of African origin, which exhibited resistance to concentrations of up to 100.0 μg/mL. The spontaneous mutation frequency for resistance to benomyl was 1.25 × 10-7. Azoxystrobin, even at high concentrations, did not inhibit mycelial growth in any of the strains, but significantly reduced sporulation rates, by as much as 100%, at a concentration of 5.0 μg/mL. Variations in sensitivity across strains, particularly to the strobilurin azoxystrobin, are possibly related to genetic variability in G. citricarpa isolates. PMID:24031363

  16. Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel

    PubMed Central

    Pinto-Almeida, António; Mendes, Tiago; de Oliveira, Rosimeire Nunes; Corrêa, Sheila de Andrade Penteado; Allegretti, Silmara Marques; Belo, Silvana; Tomás, Ana; Anibal, Fernanda de Freitas; Carrilho, Emanuel; Afonso, Ana

    2016-01-01

    Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ-susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants. PMID:27199925

  17. Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel.

    PubMed

    Pinto-Almeida, António; Mendes, Tiago; de Oliveira, Rosimeire Nunes; Corrêa, Sheila de Andrade Penteado; Allegretti, Silmara Marques; Belo, Silvana; Tomás, Ana; Anibal, Fernanda de Freitas; Carrilho, Emanuel; Afonso, Ana

    2016-01-01

    Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ-susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants. PMID:27199925

  18. Metabolism of a 5-nitroimidazole in susceptible and resistant isogenic strains of Bacteroides fragilis.

    PubMed Central

    Carlier, J P; Sellier, N; Rager, M N; Reysset, G

    1997-01-01

    We investigated the metabolism of dimetridazole (1,2-dimethyl-5-nitroimidazole) (DMZ) by the resting cell method in a susceptible strain of Bacteroides fragilis and in the same strain containing the nimA gene, which conferred resistance to 5-nitroimidazole drugs. In both cases, under strict anaerobic conditions DMZ was metabolized without major ring cleavage or nitrate formation. However, one of two distinct metabolic pathways is involved, depending on the susceptibility of the strain. In the susceptible strain, the classical reduction pathway of nitroaromatic compounds is followed at least as far as the nitroso-radical anion, with further formation of the azo-dimer: 5,5'-azobis-(1,2-dimethylimidazole). In the resistant strain, DMZ is reduced to the amine derivative, namely, 5-amino-1,2-dimethylimidazole, preventing the formation of the toxic form of the drug. The specificity of the six-electron reduction of the nitro group, which is restricted to 4- and 5-nitroimidazole, suggests an enzymatic reaction. We thus conclude that nimA and related genes may encode a 5-nitroimidazole reductase. PMID:9210672

  19. High Affinity Inha Inhibitors with Activity Against Drug-Resistant Strains of Mycobacterium Tuberculosis

    SciTech Connect

    Sullivan,T.; Truglio, J.; Boyne, M.; Novichenok, P.; Zhang, X.; Stratton, C.; Li, H.; Kaur, T.; Amin, A.; et al.

    2006-01-01

    Novel chemotherapeutics for treating multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) are required to combat the spread of tuberculosis, a disease that kills more than 2 million people annually. Using structure-based drug design, we have developed a series of alkyl diphenyl ethers that are uncompetitive inhibitors of InhA, the enoyl reductase enzyme in the MTB fatty acid biosynthesis pathway. The most potent compound has a Ki{prime} value of 1 nM for InhA and MIC{sub 99} values of 2-3 {micro}g mL{sup -1} (6-10 {micro}M) for both drug-sensitive and drug-resistant strains of MTB. Overexpression of InhA in MTB results in a 9-12-fold increase in MIC{sub 99}, consistent with the belief that these compounds target InhA within the cell. In addition, transcriptional response studies reveal that the alkyl diphenyl ethers fail to upregulate a putative efflux pump and aromatic dioxygenase, detoxification mechanisms that are triggered by the lead compound triclosan. These diphenyl ether-based InhA inhibitors do not require activation by the mycobacterial KatG enzyme, thereby circumventing the normal mechanism of resistance to the front line drug isoniazid (INH) and thus accounting for their activity against INH-resistant strains of MTB.

  20. Establishment of Stable, Cell-Mediated Immunity that Makes "Susceptible" Mice Resistant to Leishmania major

    NASA Astrophysics Data System (ADS)

    Bretscher, Peter A.; Wei, Guojian; Menon, Juthika N.; Bielefeldt-Ohmann, Helle

    1992-07-01

    Cell-mediated, but not antibody-mediated, immune responses protect humans against certain pathogens that produce chronic diseases such as leishmaniasis. Effective vaccination against such pathogens must therefore produce an immunological "imprint" so that stable, cell-mediated immunity is induced in all individuals after natural infection. BALB/c mice "innately susceptible" to Leishmania major produce antibodies after substantial infection. In the present study, "susceptible" mice injected with a small number of parasites mounted a cell-mediated response and acquired resistance to a larger, normally pathogenic, challenge. This vaccination strategy may be applicable in diseases in which protection is dependent on cell-mediated immunity.

  1. Partial characterization of an endemic strain of a methicillin- and aminoglycoside-resistant Staphylococcus aureus (MARSA) homogeneously resistant to beta-lactam antibiotics.

    PubMed

    Jacob, J; Meers, P D

    1992-06-01

    Selected strains of methicillin- and aminoglycoside-resistant Staphylococcus aureus (MARSA) were subjected to a preliminary examination. They were representative of a larger group collected in a routine clinical microbiology laboratory over a period of 2 years. MARSA was endemic in the associated hospital. The characteristics investigated were antimicrobial resistance, the production of beta-lactamase, free and bound coagulase, protein A, DNA-ase, urease, lipase and pigment. The MARSA strains were generally indistinguishable, other than in their antimicrobial resistances. The resistance to methicillin was completely homogeneous. Except with imipenem, growth extended to the edge of discs containing methicillin and the other beta-lactam antibiotics tested when the strains were cultured at 37 degrees C on media without added salt. Homogeneous resistance may confer an epidemiological advantage on strains of this phenotype. PMID:1353087

  2. Modified Bacillus thuringiensis Toxins and a Hybrid B. thuringiensis Strain Counter Greenhouse-Selected Resistance in Trichoplusia ni▿

    PubMed Central

    Franklin, Michelle T.; Nieman, Christal L.; Janmaat, Alida F.; Soberón, Mario; Bravo, Alejandra; Tabashnik, Bruce E.; Myers, Judith H.

    2009-01-01

    Resistance of greenhouse-selected strains of the cabbage looper, Trichoplusia ni, to Bacillus thuringiensis subsp. kurstaki was countered by a hybrid strain of B. thuringiensis and genetically modified toxins Cry1AbMod and Cry1AcMod, which lack helix α-1. Resistance to Cry1AbMod and Cry1AcMod was >100-fold less than resistance to native toxins Cry1Ab and Cry1Ac. PMID:19592525

  3. Strain- and Age-dependent Hippocampal Neuron Sodium Currents Correlate with Epilepsy Severity in Dravet Syndrome Mice

    PubMed Central

    Mistry, Akshitkumar M.; Thompson, Christopher H.; Miller, Alison R.; Vanoye, Carlos G.; George, Alfred L.; Kearney, Jennifer A.

    2014-01-01

    Heterozygous loss-of-function SCN1A mutations cause Dravet syndrome, an epileptic encephalopathy of infancy that exhibits variable clinical severity. We utilized a heterozygous Scn1a knockout (Scn1a+/−) mouse model of Dravet syndrome to investigate the basis for phenotype variability. These animals exhibit strain-dependent seizure severity and survival. Scn1a+/− mice on strain 129S6/SvEvTac (129.Scn1a+/−) have no overt phenotype and normal survival compared with Scn1a+/− mice bred to C57BL/6J (F1.Scn1a+/−) that have severe epilepsy and premature lethality. We tested the hypothesis that strain differences in sodium current (INa) density in hippocampal neurons contribute to these divergent phenotypes. Whole-cell voltage-clamp recording was performed on acutely-dissociated hippocampal neurons from postnatal day 21–24 (P21–24) 129.Scn1a+/− or F1.Scn1a+/− mice and wild-type littermates. INa density was lower in GABAergic interneurons from F1.Scn1a+/− mice compared to wild-type littermates, while on the 129 strain there was no difference in GABAergic interneuron INa between 129.Scn1a+/− mice and wild-type littermate controls. By contrast, INa density was elevated in pyramidal neurons from both 129.Scn1a+/− and F1.Scn1a+/− mice, and was correlated with more frequent spontaneous action potential firing in these neurons, as well as more sustained firing in F1.Scn1a+/− neurons. We also observed age-dependent differences in pyramidal neuron INa density between wild-type and Scn1a+/− animals. We conclude that preserved INa density in GABAergic interneurons contributes to the milder phenotype of 129.Scn1a+/− mice. Furthermore, elevated INa density in excitatory pyramidal neurons at P21–24 correlates with age-dependent onset of lethality in F1.Scn1a+/− mice. Our findings illustrate differences in hippocampal neurons that may underlie strain- and age-dependent phenotype severity in a Dravet syndrome mouse model, and emphasize a contribution of

  4. Blocking Hsp70 Enhances the Efficiency of Amphotericin B Treatment against Resistant Aspergillus terreus Strains

    PubMed Central

    Blatzer, Michael; Blum, Gerhard; Jukic, Emina; Posch, Wilfried; Gruber, Peter; Nagl, Markus; Binder, Ulrike; Maurer, Elisabeth; Sarg, Bettina; Lindner, Herbert; Lass-Flörl, Cornelia

    2015-01-01

    The polyene antifungal amphotericin B (AmB) is widely used to treat life-threatening fungal infections. Even though AmB resistance is exceptionally rare in fungi, most Aspergillus terreus isolates exhibit an intrinsic resistance against the drug in vivo and in vitro. Heat shock proteins perform a fundamental protective role against a multitude of stress responses, thereby maintaining protein homeostasis in the organism. In this study, we elucidated the role of heat shock protein 70 (Hsp70) family members and compared resistant and susceptible A. terreus clinical isolates. The upregulation of cytoplasmic Hsp70 members at the transcriptional as well as translational levels was significantly higher with AmB treatment than without AmB treatment, particularly in resistant A. terreus isolates, thereby indicating a role of Hsp70 proteins in the AmB response. We found that Hsp70 inhibitors considerably increased the susceptibility of resistant A. terreus isolates to AmB but exerted little impact on susceptible isolates. Also, in in vivo experiments, using the Galleria mellonella infection model, cotreatment of resistant A. terreus strains with AmB and the Hsp70 inhibitor pifithrin-μ resulted in significantly improved survival compared with that achieved with AmB alone. Our results point to an important mechanism of regulation of AmB resistance by Hsp70 family members in A. terreus and suggest novel drug targets for the treatment of infections caused by resistant fungal isolates. PMID:25870060

  5. Blocking Hsp70 enhances the efficiency of amphotericin B treatment against resistant Aspergillus terreus strains.

    PubMed

    Blatzer, Michael; Blum, Gerhard; Jukic, Emina; Posch, Wilfried; Gruber, Peter; Nagl, Markus; Binder, Ulrike; Maurer, Elisabeth; Sarg, Bettina; Lindner, Herbert; Lass-Flörl, Cornelia; Wilflingseder, Doris

    2015-07-01

    The polyene antifungal amphotericin B (AmB) is widely used to treat life-threatening fungal infections. Even though AmB resistance is exceptionally rare in fungi, most Aspergillus terreus isolates exhibit an intrinsic resistance against the drug in vivo and in vitro. Heat shock proteins perform a fundamental protective role against a multitude of stress responses, thereby maintaining protein homeostasis in the organism. In this study, we elucidated the role of heat shock protein 70 (Hsp70) family members and compared resistant and susceptible A. terreus clinical isolates. The upregulation of cytoplasmic Hsp70 members at the transcriptional as well as translational levels was significantly higher with AmB treatment than without AmB treatment, particularly in resistant A. terreus isolates, thereby indicating a role of Hsp70 proteins in the AmB response. We found that Hsp70 inhibitors considerably increased the susceptibility of resistant A. terreus isolates to AmB but exerted little impact on susceptible isolates. Also, in in vivo experiments, using the Galleria mellonella infection model, cotreatment of resistant A. terreus strains with AmB and the Hsp70 inhibitor pifithrin-μ resulted in significantly improved survival compared with that achieved with AmB alone. Our results point to an important mechanism of regulation of AmB resistance by Hsp70 family members in A. terreus and suggest novel drug targets for the treatment of infections caused by resistant fungal isolates. PMID:25870060

  6. Protective role of TNF-α, IL-10 and IL-2 in mice infected with the Oshima strain of Tick-borne encephalitis virus

    PubMed Central

    Tun, Mya Myat Ngwe; Aoki, Kotaro; Senba, Masachika; Buerano, Corazon C.; Shirai, Kenji; Suzuki, Ryuji; Morita, Kouichi; Hayasaka, Daisuke

    2014-01-01

    Tick-borne encephalitis virus (TBEV) causes acute central nervous system disease. Here, we investigated the roles of the TNF-α, IL-10 and other cytokines in appropriate KO mice following infection with Oshima and Sofjin strains of TBEV. Following infection with the Oshima strain, mortality rates were significantly increased in TNF-α KO and IL-10 KO mice compared with wild type (WT) mice. These results suggested that TNF-α and IL-10 play protective roles against fatal infection due to Oshima strain infection. However, viral loads and proinflammatory cytokine levels in the brain of TNF-α KO andIL-10 KO mice were not significantly different compared with those of WT mice. On the other hand, all WT, TNF-α KO and IL-10 KO mice died following infection with Sofjin strain. Interestingly, Sofjin-infected mice did not exhibit an up-regulated mRNA level of IL-2 in the spleen in all groups of mice, whereas Oshima-infected mice showed significantly increased level of IL-2 compared with mock-infected mice. From these results, we suggest that TNF-α, IL-10 and IL-2 are key factors for disease remission from fatal encephalitis due to infection with Oshima strain of TBEV. PMID:24938868

  7. The Calculated and Measured Resistance for Splices between Conductors in a MICE Superconducting Coil

    SciTech Connect

    Green, Michael A.; Dietderich, Dan; Higley, Hugh; Pan, Heng; Tam, Darren; Trillaud, Federic; Wang, Li; Wu, Hong; Xu, Feng Yu

    2009-03-19

    The resistance of superconducting joints within MICE coils is an important issue particularly for the coupling coils. The MICE tracker solenoids have only two superconducting joints in the three spectrometer set (end coil 1, the center coil and end coil 2). The AFC magnets may have only a single joint within the coil. The coupling coils may have as many as fifteen joints within the coil, due to relatively short piece lengths of the superconductor. LBNL and ICST looked at three types of coil joints. They are: (1) cold fusion butt joints, (2) side-by-side lap joints, and (3) up-down lap joints. A theoretical calculation of the joint resistance was done at LBNL and checked by ICST. After looking at the theoretical resistance of the three types of joints, it was decided that the cold welded butt joint was not an attractive alternative for joints within a MICE superconducting magnet coil. Side-by-side and up-down lap joints were fabricated at ICST using two types of soft solder between the conductors. These conductor joints were tested at LBNL at liquid helium temperatures over a range of magnetic fields. The joint resistance was compared with the theoretical calculations. Measurements of splice strength were also made at 300 K and 77 K.

  8. Piperitone from Mentha longifolia var. chorodictya Rech F. reduces the nitrofurantoin resistance of strains of enterobacteriaceae.

    PubMed

    Shahverdi, A R; Rafii, F; Tavassoli, F; Bagheri, M; Attar, F; Ghahraman, A

    2004-11-01

    The diluted essential oil of Mentha longifolia (L.) var. chlorodictya Rech F. foliage enhanced the bactericidal activity of nitrofurantoin decreasing the minimum inhibitory concentration (MIC) of nitrofurantoin for nitrofurantoin-resistant strains of Enterobacteriaceae. Thin-layer chromatography (TLC) analysis of the essential oil detected a fraction (R(f) = 0.35, UV lambda(max) of 232.5), which was the most effective in enhancement of nitrofurantoin activity. Using gas liquid chromatography and known standards, the active fraction was identified as piperitone. 1 microl of the piperitone fraction decreased the MIC of nitrofurantoin 3-20 fold for the different strains of Enterobacteriaceae tested. PMID:15597306

  9. Extended-Spectrum Cephalosporin-Resistant Salmonella enterica serovar Heidelberg Strains, the Netherlands(1).

    PubMed

    Liakopoulos, Apostolos; Geurts, Yvon; Dierikx, Cindy M; Brouwer, Michael S M; Kant, Arie; Wit, Ben; Heymans, Raymond; van Pelt, Wilfrid; Mevius, Dik J

    2016-07-01

    Extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg strains (JF6X01.0022/XbaI.0251, JF6X01.0326/XbaI.1966, JF6X01.0258/XbaI.1968, and JF6X01.0045/XbaI.1970) have been identified in the United States with pulsed-field gel electrophoresis. Our examination of isolates showed introduction of these strains in the Netherlands and highlight the need for active surveillance and intervention strategies by public health organizations. PMID:27314180

  10. Azole resistance in oropharyngeal Candida albicans strains isolated from patients infected with human immunodeficiency virus.

    PubMed Central

    He, X; Tiballi, R N; Zarins, L T; Bradley, S F; Sangeorzan, J A; Kauffman, C A

    1994-01-01

    For 212 oropharyngeal isolates of Candida albicans, the fluconazole MICs for 50 and 90% of strains tested were 0.5 and 16 micrograms/ml, respectively, and those of itraconazole were 0.05 and 0.2 micrograms/ml, respectively. Of 16 isolates for which fluconazole MICs were > 64 micrograms/ml, itraconazole MICs for 14 were < or = 0.8 micrograms/ml and for 2 were > 6.4 micrograms/ml. Most fluconazole-resistant strains remained susceptible to itraconazole; whether itraconazole will prove effective for refractory thrush remains to be shown. PMID:7840596

  11. Efficient recovery of fluoroquinolone-susceptible and fluoroquinolone-resistant Escherichia coli strains from frozen samples.

    PubMed

    Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N; Harris, Anthony D; Smith, Catherine A; Maslow, Joel

    2008-04-01

    We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples. PMID:18279070

  12. Extended-Spectrum Cephalosporin-Resistant Salmonella enterica serovar Heidelberg Strains, the Netherlands1

    PubMed Central

    Geurts, Yvon; Dierikx, Cindy M.; Brouwer, Michael S.M.; Kant, Arie; Wit, Ben; Heymans, Raymond; van Pelt, Wilfrid; Mevius, Dik J.

    2016-01-01

    Extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg strains (JF6X01.0022/XbaI.0251, JF6X01.0326/XbaI.1966, JF6X01.0258/XbaI.1968, and JF6X01.0045/XbaI.1970) have been identified in the United States with pulsed-field gel electrophoresis. Our examination of isolates showed introduction of these strains in the Netherlands and highlight the need for active surveillance and intervention strategies by public health organizations. PMID:27314180

  13. Efficient Recovery of Fluoroquinolone-Susceptible and Fluoroquinolone-Resistant Escherichia coli Strains From Frozen Samples

    PubMed Central

    Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N.; Harris, Anthony D.; Smith, Catherine A.; Maslow, Joel

    2010-01-01

    We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples. PMID:18279070

  14. Real-time PCR based analysis of metal resistance genes in metal resistant Pseudomonas aeruginosa strain J007.

    PubMed

    Choudhary, Sangeeta; Sar, Pinaki

    2016-07-01

    A uranium (U)-resistant and -accumulating Pseudomonas aeruginosa strain was characterized to assess the response of toxic metals toward its growth and expression of metal resistance determinants. The bacterium showed MIC (minimum inhibitory concentration) values of 6, 3, and 2 mM for Zn, Cu, and Cd, respectively; with resistance phenotype conferred by periplasmic Cu sequestering copA and RND type heavy metal efflux czcA genes. Real-time PCR-based expression analysis revealed significant upregulation of both these genes upon exposure to low concentrations of metals for short duration, whereas the global stress response gene sodA encoding superoxide dismutase enzyme was upregulated only at higher metal concentrations or longer exposure time. It could also be inferred that copA and czcA are involved in providing resistance only at low metal concentrations, whereas involvement of "global stress response" phenomenon (expression of sodA) at higher metal concentration or increased exposure was evident. This study provides significant understanding of the adaptive response of bacteria surviving in metal and radionuclide contaminated environments along with the development of real-time PCR-based quantification method of using metal resistance genes as biomarker for monitoring relevant bacteria in such habitats. PMID:26662317

  15. Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454.

    PubMed

    Magnet, S; Courvalin, P; Lambert, T

    2001-12-01

    Multidrug-resistant strain Acinetobacter baumannii BM4454 was isolated from a patient with a urinary tract infection. The adeB gene, which encodes a resistance-nodulation-cell division (RND) protein, was detected in this strain by PCR with two degenerate oligodeoxynucleotides. Insertional inactivation of adeB in BM4454, which generated BM4454-1, showed that the corresponding protein was responsible for aminoglycoside resistance and was involved in the level of susceptibility to other drugs including fluoroquinolones, tetracyclines, chloramphenicol, erythromycin, trimethoprim, and ethidium bromide. Study of ethidium bromide accumulation in BM4454 and BM4454-1, in the presence or in the absence of carbonyl cyanide m-chlorophenylhydrazone, demonstrated that AdeB was responsible for the decrease in intracellular ethidium bromide levels in a proton motive force-dependent manner. The adeB gene was part of a cluster that included adeA and adeC which encodes proteins homologous to membrane fusion and outer membrane proteins of RND-type three-component efflux systems, respectively. The products of two upstream open reading frames encoding a putative two-component regulatory system might be involved in the regulation of expression of the adeABC gene cluster. PMID:11709311

  16. Resistance-Nodulation-Cell Division-Type Efflux Pump Involved in Aminoglycoside Resistance in Acinetobacter baumannii Strain BM4454

    PubMed Central

    Magnet, Sophie; Courvalin, Patrice; Lambert, Thierry

    2001-01-01

    Multidrug-resistant strain Acinetobacter baumannii BM4454 was isolated from a patient with a urinary tract infection. The adeB gene, which encodes a resistance-nodulation-cell division (RND) protein, was detected in this strain by PCR with two degenerate oligodeoxynucleotides. Insertional inactivation of adeB in BM4454, which generated BM4454-1, showed that the corresponding protein was responsible for aminoglycoside resistance and was involved in the level of susceptibility to other drugs including fluoroquinolones, tetracyclines, chloramphenicol, erythromycin, trimethoprim, and ethidium bromide. Study of ethidium bromide accumulation in BM4454 and BM4454-1, in the presence or in the absence of carbonyl cyanide m-chlorophenylhydrazone, demonstrated that AdeB was responsible for the decrease in intracellular ethidium bromide levels in a proton motive force-dependent manner. The adeB gene was part of a cluster that included adeA and adeC which encodes proteins homologous to membrane fusion and outer membrane proteins of RND-type three-component efflux systems, respectively. The products of two upstream open reading frames encoding a putative two-component regulatory system might be involved in the regulation of expression of the adeABC gene cluster. PMID:11709311

  17. Role of volatile fatty acids in colonization resistance to Clostridium difficile in gnotobiotic mice.

    PubMed Central

    Su, W J; Waechter, M J; Bourlioux, P; Dolegeal, M; Fourniat, J; Mahuzier, G

    1987-01-01

    Clostridium difficile is an agent involved in the development of antibiotic-associated pseudomembranous colitis. The purpose of this work was to investigate the role of volatile fatty acids (VFAs) in resistance to colonization by C. difficile by using a gnotobiotic animal model. Accordingly, germfree mice were associated with different hamster flora, and the VFAs in their cecal contents were measured by gas chromatography. The results showed that VFAs were produced mainly by the intestinal flora, especially by the strictly anaerobic bacteria. In these associated mice, the concentrations of acetic, propionic, and butyric acids were higher than those of other acids, but at pH 6.8 the MICs of these three acids in vitro for C. difficile were more than 200 mu eq/ml. In gnotobiotic mice monoassociated with C. difficile and in the isolated ceca of these mice, VFAs did not inhibit the growth of C. difficile. In gnotobiotic mice which were diassociated with C. difficile and C. butyricum and given drinking water with a lactose concentration of 20%, the cecal contents included about the same amount of butyric acid as did those of the monoassociated mice, although the population of C. difficile remained the same. Therefore, it is suggested that VFAs alone cannot inhibit intestinal colonization by C. difficile and that, consequently, other inhibitory mechanisms are also present. PMID:3596806

  18. First Report of an OXA-48-Producing Multidrug-Resistant Proteus mirabilis Strain from Gaza, Palestine

    PubMed Central

    Chen, Liang; Chavda, Kalyan D.; Mediavilla, Jose R.; Jacobs, Michael R.; Bonomo, Robert A.

    2015-01-01

    We report the first multidrug-resistant Proteus mirabilis strain producing the carbapenemase OXA-48 (Pm-OXA-48) isolated at Al-Shifa hospital in Gaza, Palestine. Draft genome sequencing of Pm-OXA-48 identified 16 antimicrobial resistance genes, encoding resistance to β-lactams, aminoglycosides, fluoroquinolones, phenicols, streptothricin, tetracycline, and trimethoprim-sulfamethoxazole. Complete sequencing of the blaOXA-48-harboring plasmid revealed that it is a 72 kb long IncL/M plasmid, harboring carbapenemase gene blaOXA-48, extended spectrum β-lactamase gene blaCTX-M-14, and aminoglycoside resistance genes strA, strB, and aph(3′)-VIb. PMID:25896692

  19. Toxigenic genes, spoilage potential, and antimicrobial resistance of Bacillus cereus group strains from ice cream.

    PubMed

    Arslan, Seza; Eyi, Ayla; Küçüksarı, Rümeysa

    2014-02-01

    Bacillus spp. can be recovered from almost every environment. It is also found readily in foods, where it may cause food spoilage and/or food poisoning due to its toxigenic and pathogenic nature, and extracellular enzymes. In this study, 29 Bacillus cereus group strains from ice cream were examined for the presence of following virulence genes hblC, nheA, cytK and ces genes, and tested for a range of the extracellular enzymes, and antimicrobial susceptibility. The strains were found to produce extracellular enzymes: proteolytic and lipolytic activity, gelatin hydrolysis and lecithinase production (100%), DNase production (93.1%) and amylase activity (93.1%). Of 29 strains examined, 24 (82.8%) showed hemolytic activity on blood agar. Beta-lactamase enzyme was only produced by 20.7% of B. cereus group. Among 29 B. cereus group from ice cream, nheA was the most common virulence gene detected in 44.8% of the strains, followed by hblC gene with 17.2%. Four (13.8%) of the 29 strains were positive for both hblC gene and nheA gene. Contrarily, cytK and ces genes were not detected in any of the strains. Antimicrobial susceptibility of ice cream isolates was tested to 14 different antimicrobial agents using the disc diffusion method. We detected resistance to penicillin and ampicillin with the same rate of 89.7%. Thirty-one percent of the strains were multiresistant to three or more antibiotics. This study emphasizes that the presence of natural isolates of Bacillus spp. harboring one or more enterotoxin genes, producing extracellular enzymes which may cause spoilage and acquiring antibiotic resistance might hold crucial importance in the food safety and quality. PMID:24309214

  20. Gene-related strain variation of Staphylococcus aureus for homologous resistance response to acid stress.

    PubMed

    Lee, Soomin; Ahn, Sooyeon; Lee, Heeyoung; Kim, Won-Il; Kim, Hwang-Yong; Ryu, Jae-Gee; Kim, Se-Ri; Choi, Kyoung-Hee; Yoon, Yohan

    2014-10-01

    This study investigated the effect of adaptation of Staphylococcus aureus strains to the acidic condition of tomato in response to environmental stresses, such as heat and acid. S. aureus ATCC 13565, ATCC 14458, ATCC 23235, ATCC 27664, and NCCP10826 habituated in tomato extract at 35°C for 24 h were inoculated in tryptic soy broth. The culture suspensions were then subjected to heat challenge or acid challenge at 60°C and pH 3.0, respectively, for 60 min. In addition, transcriptional analysis using quantitative real-time PCR was performed to evaluate the expression level of acid-shock genes, such as clpB, zwf, nuoF, and gnd, from five S. aureus strains after the acid habituation of strains in tomato at 35°C for 15 min and 60 min in comparison with that of the nonhabituated strains. In comparison with the nonhabituated strains, the five tomato-habituated S. aureus strains did not show cross protection to heat, but tomato-habituated S. aureus ATCC 23235 showed acid resistance. In quantitative real-time-PCR analysis, the relative expression levels of acid-shock genes (clpB, zwf, nuoF, and gnd) were increased the most in S. aureus ATCC 23235 after 60 min of tomato habituation, but there was little difference in the expression levels among the five S. aureus strains after 15 min of tomato habituation. These results indicate that the variation of acid resistance of S. aureus is related to the expression of acid-shock genes during acid habituation. PMID:25285500

  1. A quantitative analysis of the effects of qualitatively different reinforcers on fixed ratio responding in inbred strains of mice.

    PubMed

    Hutsell, Blake A; Newland, M Christopher

    2013-03-01

    Previous studies of inbred mouse strains have shown reinforcer-strain interactions that may potentially mask differences among strains in memory performance. The present research examined the effects of two qualitatively different reinforcers (heterogeneous mix of flavored pellets and sweetened-condensed milk) on responding maintained by fixed-ratio schedules of reinforcement in three inbred strains of mice (BALB/c, C57BL/6, and DBA/2). Responses rates for all strains were a bitonic (inverted U) function of the size of the fixed-ratio schedule and were generally higher when responding was maintained by milk. For the DBA/2 and C57BL/6 and to a lesser extent the BALB/c, milk primarily increased response rates at moderate fixed ratios, but not at the largest fixed ratios tested. A formal model of ratio-schedule performance, Mathematical Principles of Reinforcement (MPR), was applied to the response rate functions of individual mice. According to MPR, the differences in response rates maintained by pellets and milk were mostly due to changes in motoric processes as indicated by changes in the minimum response time (δ) produced by each reinforcer type and not specific activation (a), a model term that represents value and is correlated with reinforcer magnitude and the break point obtained under progressive ratio schedules. MPR also revealed that, although affected by reinforcer type, a parameter interpreted as the rate of saturation of working memory (λ), differed among the strains. PMID:23357283

  2. An enterotoxin-negative strain of Yersinia enterocolitica serotype O:3 is capable of producing diarrhea in mice.

    PubMed Central

    Schiemann, D A

    1981-01-01

    A strain of Yersinia enterocolitica serotype O:3 that consistently produced heat-stable enterotoxin at 22 but not at 37 degrees C and another strain of the same serotype which did not produce enterotoxin at 22 degrees C were both positive for autoagglutination at 35 degrees C, a test that has been related to virulence in yersiniae. Both strains were infective for HeLa cells and produced guinea pig conjunctivitis. Mice infected with either strain through their drinking water developed diarrhea and excreted the organism in high numbers in the feces. A control strain of serotype O:3 positive for enterotoxin and HeLa cell infectivity but negative for autoagglutination was avirulent. Extracts of feces and intestines from mice with diarrhea were negative for enterotoxin. The results indicate that the heat-stable enterotoxin produced in vitro by some strains of Y. enterocolitica and measured by the infant mouse assay plays no role in pathogenesis as described by the mouse diarrhea model. PMID:7251137

  3. Biological characteristics of different epidemic enterovirus 71 strains and their pathogeneses in neonatal mice and rhesus monkeys.

    PubMed

    Zhongping, Xie; Hua, Li; Ting, Yang; Zhengling, Liu; Min, Feng; Tianhong, Xie; Runxiang, Long; Dong, Shen; Guangju, Jiang; Lei, Yue; Rong, Yang; Fangyu, Luo; Qihan, Li

    2016-02-01

    Hand, foot and mouth disease (HFMD) has been prevalent in China since 2008. Enterovirus 71 (EV71) is a common causative agent of HFMD, and various strains of EV71 are prevalent worldwide. The EV71C4 subgenotype is the most endemic strain in China. However, few studies investigating the biological characteristics and pathogeneses of different C4 strains have been reported. Therefore, the current study investigated 19 clinical EV71 strains in neonatal ICR mice and neonatal rhesus monkeys by comparing pathogenicity; the virulence of different viral passages, dosages, and routes of infection; and the effects produced by subject animal age. These 19 clinical EV71 strains, which were of the same subtype, displayed varying pathogenic effects. Three strains (HE31, 231 and 262) induced limb paralysis in neonatal ICR mice. In addition, the degree of virulence was largely dependent upon the dose, route of infection, and number of passages of the challenge virus, as well as the ages of the infected animals. The present study provides valuable basic data to enable further research into EV71 pathogenesis and to facilitate the development of new drugs and vaccines. PMID:26555165

  4. Selection and Characterization of Phage-Resistant Mutant Strains of Listeria monocytogenes Reveal Host Genes Linked to Phage Adsorption

    PubMed Central

    Denes, Thomas; den Bakker, Henk C.; Tokman, Jeffrey I.; Guldimann, Claudia

    2015-01-01

    Listeria-infecting phages are readily isolated from Listeria-containing environments, yet little is known about the selective forces they exert on their host. Here, we identified that two virulent phages, LP-048 and LP-125, adsorb to the surface of Listeria monocytogenes strain 10403S through different mechanisms. We isolated and sequenced, using whole-genome sequencing, 69 spontaneous mutant strains of 10403S that were resistant to either one or both phages. Mutations from 56 phage-resistant mutant strains with only a single mutation mapped to 10 genes representing five loci on the 10403S chromosome. An additional 12 mutant strains showed two mutations, and one mutant strain showed three mutations. Two of the loci, containing seven of the genes, accumulated the majority (n = 64) of the mutations. A representative mutant strain for each of the 10 genes was shown to resist phage infection through mechanisms of adsorption inhibition. Complementation of mutant strains with the associated wild-type allele was able to rescue phage susceptibility for 6 out of the 10 representative mutant strains. Wheat germ agglutinin, which specifically binds to N-acetylglucosamine, bound to 10403S and mutant strains resistant to LP-048 but did not bind to mutant strains resistant to only LP-125. We conclude that mutant strains resistant to only LP-125 lack terminal N-acetylglucosamine in their wall teichoic acid (WTA), whereas mutant strains resistant to both phages have disruptive mutations in their rhamnose biosynthesis operon but still possess N-acetylglucosamine in their WTA. PMID:25888172

  5. Selection and Characterization of Phage-Resistant Mutant Strains of Listeria monocytogenes Reveal Host Genes Linked to Phage Adsorption.

    PubMed

    Denes, Thomas; den Bakker, Henk C; Tokman, Jeffrey I; Guldimann, Claudia; Wiedmann, Martin

    2015-07-01

    Listeria-infecting phages are readily isolated from Listeria-containing environments, yet little is known about the selective forces they exert on their host. Here, we identified that two virulent phages, LP-048 and LP-125, adsorb to the surface of Listeria monocytogenes strain 10403S through different mechanisms. We isolated and sequenced, using whole-genome sequencing, 69 spontaneous mutant strains of 10403S that were resistant to either one or both phages. Mutations from 56 phage-resistant mutant strains with only a single mutation mapped to 10 genes representing five loci on the 10403S chromosome. An additional 12 mutant strains showed two mutations, and one mutant strain showed three mutations. Two of the loci, containing seven of the genes, accumulated the majority (n = 64) of the mutations. A representative mutant strain for each of the 10 genes was shown to resist phage infection through mechanisms of adsorption inhibition. Complementation of mutant strains with the associated wild-type allele was able to rescue phage susceptibility for 6 out of the 10 representative mutant strains. Wheat germ agglutinin, which specifically binds to N-acetylglucosamine, bound to 10403S and mutant strains resistant to LP-048 but did not bind to mutant strains resistant to only LP-125. We conclude that mutant strains resistant to only LP-125 lack terminal N-acetylglucosamine in their wall teichoic acid (WTA), whereas mutant strains resistant to both phages have disruptive mutations in their rhamnose biosynthesis operon but still possess N-acetylglucosamine in their WTA. PMID:25888172

  6. Myeloid Dendritic Cells (DCs) of Mice Susceptible to Paracoccidioidomycosis Suppress T Cell Responses whereas Myeloid and Plasmacytoid DCs from Resistant Mice Induce Effector and Regulatory T Cells

    PubMed Central

    Pina, Adriana; Frank de Araujo, Eliseu; Felonato, Maíra; Loures, Flávio V.; Feriotti, Claudia; Bernardino, Simone; Barbuto, José Alexandre M.

    2013-01-01

    The protective adaptive immune response in paracoccidioidomycosis, a mycosis endemic among humans, is mediated by T cell immunity, whereas impaired T cell responses are associated with severe, progressive disease. The early host response to Paracoccidioides brasiliensis infection is not known since the disease is diagnosed at later phases of infection. Our laboratory established a murine model of infection where susceptible mice reproduce the severe disease, while resistant mice develop a mild infection. This work aimed to characterize the influence of dendritic cells in the innate and adaptive immunity of susceptible and resistant mice. We verified that P. brasiliensis infection induced in bone marrow-derived dendritic cells (DCs) of susceptible mice a prevalent proinflammatory myeloid phenotype that secreted high levels of interleukin-12 (IL-12), tumor necrosis factor alpha, and IL-β, whereas in resistant mice, a mixed population of myeloid and plasmacytoid DCs secreting proinflammatory cytokines and expressing elevated levels of secreted and membrane-bound transforming growth factor β was observed. In proliferation assays, the proinflammatory DCs from B10.A mice induced anergy of naïve T cells, whereas the mixed DC subsets from resistant mice induced the concomitant proliferation of effector and regulatory T cells (Tregs). Equivalent results were observed during pulmonary infection. The susceptible mice displayed preferential expansion of proinflammatory myeloid DCs, resulting in impaired proliferation of effector T cells. Conversely, the resistant mice developed myeloid and plasmacytoid DCs that efficiently expanded gamma interferon-, IL-4-, and IL-17-positive effector T cells associated with increased development of Tregs. Our work highlights the deleterious effect of excessive innate proinflammatory reactions and provides new evidence for the importance of immunomodulation during pulmonary paracoccidioidomycosis. PMID:23340311

  7. Insecticide resistance in two Aedes aegypti (Diptera: Culicidae) strains from Costa Rica.

    PubMed

    Bisset, J A; Marín, R; Rodríguez, M M; Severson, D W; Ricardo, Y; French, L; Díaz, M; Pérez, O

    2013-03-01

    Dengue (family Flaviridae, genus Flavivirus, DENV) and dengue hemorrhagic fever (DHF) are presently important public health problems in Costa Rica. The primary strategy for disease control is based on reducing population densities of the main mosquito vector Aedes aegypti (L.) (Diptera: Culicidae). This is heavily dependent on use of chemical insecticides, thus the development of resistance is a frequent threat to control program effectiveness. The objective of this study was to determine the levels of insecticide resistance and the metabolic resistance mechanisms involved in two Ae. aegypti strains collected from two provinces (Puntarenas and Limon) in Costa Rica. Bioassays with larvae were performed according to World Health Organization guidelines and resistance in adults was measured through standard bottle assays. The activities of beta-esterases, cytochrome P450 monooxygenases, and glutathione S-transferases (GST), were assayed through synergists and biochemical tests, wherein the threshold criteria for each enzyme was established using the susceptible Rockefeller strain. The results showed higher resistance levels to the organophosphate (OP) temephos and the pyrethroid deltamethrin in larvae. The efficacy of commercial formulations of temephos in controlling Ae. aegypti populations was 100% mortality up to 11 and 12 d posttreatment with daily water replacements in test containers. Temephos and deltamethrin resistance in larvae were associated with high esterase activity, but not to cytochrome P450 monooxygenase or GST activities. Adult mosquitoes were resistant to deltamethrin, and susceptible to bendiocarb, chlorpyrifos, and cypermethrin. Because temephos and deltamethrin resistance are emerging at the studied sites, alternative insecticides should be considered. The insecticides chlorpyrifos and cypermethrin could be good candidates to use as alternatives for Ae. aegypti control. PMID:23540124

  8. The global establishment of a highly-fluoroquinolone resistant Salmonella enterica serotype Kentucky ST198 strain

    PubMed Central

    Le Hello, Simon; Bekhit, Amany; Granier, Sophie A.; Barua, Himel; Beutlich, Janine; Zając, Magdalena; Münch, Sebastian; Sintchenko, Vitali; Bouchrif, Brahim; Fashae, Kayode; Pinsard, Jean-Louis; Sontag, Lucile; Fabre, Laetitia; Garnier, Martine; Guibert, Véronique; Howard, Peter; Hendriksen, Rene S.; Christensen, Jens P.; Biswas, Paritosh K.; Cloeckaert, Axel; Rabsch, Wolfgang; Wasyl, Dariusz; Doublet, Benoit; Weill, François-Xavier

    2013-01-01

    While the spread of Salmonella enterica serotype Kentucky resistant to ciprofloxacin across Africa and the Middle-East has been described recently, the presence of this strain in humans, food, various animal species (livestock, pets, and wildlife) and in environment is suspected in other countries of different continents. Here, we report results of an in-depth molecular epidemiological study on a global human and non-human collection of S. Kentucky (n = 70). We performed XbaI-pulsed field gel electrophoresis and multilocus sequence typing, assessed mutations in the quinolone resistance-determining regions, detected β-lactam resistance mechanisms, and screened the presence of the Salmonella genomic island 1 (SGI1). In this study, we highlight the rapid and extensive worldwide dissemination of the ciprofloxacin-resistant S. Kentucky ST198-X1-SGI1 strain since the mid-2000s in an increasingly large number of contaminated sources, including the environment. This strain has accumulated an increasing number of chromosomal and plasmid resistance determinants and has been identified in the Indian subcontinent, Southeast Asia and Europe since 2010. The second substitution at position 87 in GyrA (replacing the amino acid Asp) appeared helpful for epidemiological studies to track the origin of contamination. This global study provides evidence leading to the conclusion that high-level resistance to ciprofloxacin in S. Kentucky is a simple microbiological trait that facilitates the identification of the epidemic clone of interest, ST198-X1-SGI1. Taking this into account is essential in order to detect and monitor it easily and to take rapid measures in livestock to ensure control of this infection. PMID:24385975

  9. Adulticidal & larvicidal efficacy of three neonicotinoids against insecticide susceptible & resistant mosquito strains

    PubMed Central

    Uragayala, Sreehari; Verma, Vaishali; Natarajan, Elamathi; Velamuri, Poonam Sharma; Kamaraju, Raghavendra

    2015-01-01

    Background & objectives: Due to ever growing insecticide resistance in mosquitoes to commonly used insecticides in many parts of the globe, there is always a need for introduction of new insecticides for the control of resistant vector mosquitoes. In this study, larvicidal and adulticidal efficacies of three neonicotinoids (imidacloprid, thiacloprid and thiamethoxam) were tested against resistant and susceptible populations of Anopheles stephensi Liston 1901, Aedes (Stegomyia) aegypti Linnaeus, and Culex quinquefasciatus Say (Diptera: Culicidae). Methods: Laboratory-reared mosquito species were used. Insecticide susceptibility tests were done using standard WHO procedures and using diagnostic dosages of insecticide test papers and larvicides. Adulticidal efficacy of candidate insecticides was assessed using topical application method and larval bioassays were conducted using standard WHO procedure. Results: The results of topical application on 3-5 day old female mosquitoes indicated that resistant strain of An. stephensi registered lower LC50 values than the susceptible strain. Among the three insecticides tested, thiacloprid was found more effective than the other two insecticides. Culex quinquefasciatus registered lowest LC50 for imidacloprid than the other two mosquito species tested. In larval bioassays, the LC50 values registered for imidacloprid were in the order of Cx. quinquefasciatus resistant strains of mosquito species tested showed more susceptibility to the three neonicotinoids tested, and the possibility of using neonicotinoids for the control of resistant mosquitoes

  10. Lung tumorigenic interactions in strain A/J mice of five environmental polycyclic aromatic hydrocarbons.

    PubMed Central

    Nesnow, S; Mass, M J; Ross, J A; Galati, A J; Lambert, G R; Gennings, C; Carter, W H; Stoner, G D

    1998-01-01

    The binary, ternary, quaternary, and quintary interactions of a five-component mixture of carcinogenic environmental polycyclic aromatic hydrocarbons (PAHs) using response surface analyses are described. Initially, lung tumor dose-response curves in strain A/J mice for each of the individual PAHs benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), dibenz[a,h]anthracene (DBA), 5-methylchrysene (5MC), and cyclopenta[cd]pyrene (CPP) were obtained. From these data, doses were selected for the quintary mixture study based on toxicity, survival, range of response, and predicted tumor yields. The ratios of doses among PAHs were designed to simulate PAH ratios found in environmental air and combustion samples. Quintary mixtures of B[a]P, B[b]F, DBA, 5MC, and CPP were administered to male strain A/J mice in a 2(5) factorial 32-dose group dosing scheme (combinations of five PAHs each at either high or low doses) and lung adenomas were scored. Comparison of observed lung adenoma formation with that expected from additivity identified both greater than additive and less than additive interactions that were dose related i.e., greater than additive at lower doses and less than additive at higher doses. To identify specific interactions, a response surface analysis using response addition was applied to the tumor data. This response surface model contained five dose, ten binary, ten ternary, five quaternary, and one quintary parameter. This analysis produced statistically significant values of 16 parameters. The model and model parameters were evaluated by estimating the dose-response relationships for each of the five PAHs. The predicted dose-response curves for all five PAHs indicated a good estimation. The binary interaction functions were dominated for the most part by DBA and were inhibitory. The response surface model predicted, to a significant degree, the observed lung tumorigenic responses of the quintary mixtures. These data suggest that although interactions between

  11. Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

    PubMed

    Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

    2014-12-01

    Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs. PMID:25843136

  12. Risk assessment, cross-resistance potential, and biochemical mechanism of resistance to emamectin benzoate in a field strain of house fly (Musca domestica Linnaeus).

    PubMed

    Khan, Hafiz Azhar Ali; Akram, Waseem; Khan, Tiyyabah; Haider, Muhammad Saleem; Iqbal, Naeem; Zubair, Muhammad

    2016-05-01

    Reduced sensitivity to insecticides in insect pests often results in control failures and increases in the dose and frequency of applications, ultimately polluting the environment. Reduced sensitivity to emamectin benzoate, a broad-spectrum agrochemical belonging to the avermectin group of pesticides, was reported in house flies (Musca domestica L.) collected from Punjab, Pakistan, in 2013. The aim of the present study was to investigate the risk for resistance development, biochemical mechanism, and cross-resistance potential to other insecticides in an emamectin benzoate selected (EB-SEL) strain of house flies. A field-collected strain showing reduced sensitivity to emamectin was re-selected in the laboratory for five consecutive generations and compared with a laboratory susceptible (Lab-Susceptible) reference strain, using bioassays. The field strain showed rapid development of resistance to emamectin (resistance ratio (RR) increased from 35.15 to 149.26-fold) as a result of selection experiments; however, resistance declined when the selection pressure uplifted. The EB-SEL strain showed reduction in resistance to abamectin, indoxacarb, and thiamethoxam. The results of synergism experiments using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) enzyme inhibitors and biochemical analyses revealed that the metabolic resistance mechanism was not responsible in developing emamectin resistance in the EB-SEL strain. In conclusion, the risk for the rapid development of emamectin resistance under continuous selection pressure suggests using a multifaceted integrated pest management approach for house flies. Moreover, the instable nature of emamectin resistance in the EB-SEL strain and lack of cross-resistance to other insecticides provide windows for the rotational use of insecticides with different modes of action. This will ultimately reduce emamectin selection pressure and help improving management programs for house flies without polluting the

  13. Host Double Strand Break Repair Generates HIV-1 Strains Resistant to CRISPR/Cas9.