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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. Pathogenesis of acute murine cytomegalovirus infection in resistant and susceptible strains of mice.

    PubMed

    Mercer, J A; Spector, D H

    1986-02-01

    We have characterized the progress of acute murine cytomegalovirus (MCMV) infection in the spleen, liver, and salivary gland of susceptible (BALB/c) and resistant (C3H) strains of mice after intraperitoneal inoculation. Viral replication was analyzed by virus titration, infectious-center assays, and in situ cytohybridization with cloned subgenomic fragments of the MCMV genome. The most striking differences between strains were observed in the spleen. At 24 h postinfection (p.i.), both strains had a similar number of infected spleen cells. At 48 h p.i., BALB/c mice showed marked dissemination of the splenic infection which continued until 96 h p.i. In contrast, the number of infected C3H spleen cells did not increase from the 24-h level but declined later on. This early block in dissemination of MCMV infection in C3H mouse spleens was not a result of the H-2k haplotype, as BALB.K (H-2k) mice, which show an intermediate level of resistance to MCMV infection, exhibited dissemination of the infection between 24 and 48 h p.i., albeit at a reduced level. However, between 72 and 96 h p.i., we observed a decline in the number of infected spleen cells in BALB.K mice similar to that observed in C3H mice. We also demonstrated by Southern blot analysis of DNA from the infected spleen cells that the termini of the MCMV genome fuse after in vivo infection.

  3. Genetic resistance to diet-induced obesity in chromosome substitution strains of mice

    PubMed Central

    Burrage, Lindsay C.; Baskin-Hill, Annie E.; Sinasac, David S.; Singer, Jonathan B.; Croniger, Colleen M.; Kirby, Andrew; Kulbokas, E. J.; Daly, Mark J.; Lander, Eric S.; Broman, Karl W.

    2013-01-01

    Discovery of genes that confer resistance to diseases such as diet-induced obesity could have tremendous therapeutic impact. We previously demonstrated that the C57BL/6J-ChrA/J/NaJ panel of chromosome substitution strains (CSSs) is a unique model for studying resistance to diet-induced obesity. In the present study, three replicate CSS surveys showed remarkable consistency, with 13 A/J-derived chromosomes reproducibly conferring resistance to high-fat-diet-induced obesity. Twenty CSS intercrosses, one derived from each of the 19 autosomes and chromosome X, were used to determine the number and location of quantitative trait loci (QTLs) on individual chromosomes and localized six QTLs. However, analyses of mean body weight in intercross progeny versus C57BL/6J provided strong evidence that many QTLs discovered in the CSS surveys eluded detection in these CSS intercrosses. Studies of the temporal effects of these QTLs suggest that obesity resistance was dynamic, with QTLs acting at different ages or after different durations of diet exposure. Thus, these studies provide insight into the genetic architecture of complex traits such as resistance to diet-induced obesity in the C57BL/6J-ChrA/J/NaJ CSSs. Because some of the QTLs detected in the CSS intercrosses were not detected using a traditional C57BL/6J × A/J intercross, our results demonstrate that surveys of CSSs and congenic strains derived from them are useful complementary tools for analyzing complex traits. PMID:20127486

  4. Differential IL-1 synthesis by astrocytes from Theiler's murine encephalomyelitis virus-susceptible and -resistant strains of mice.

    PubMed

    Rubio, N; Capa, L

    1993-07-01

    Increasing evidence shows that interleukin-1 (IL-1) contributes to inflammatory processes, such as experimental allergic encephalomyelitis (EAE) and virus-induced demyelination, inside the central nervous system (CNS). Using primary cultures of mouse astrocytes, we show that these glial cells can be induced to produce IL-1 alpha when infected with Theiler's murine encephalomyelitis virus (TMEV). This was true for astrocytes from SJL/J mice, a strain susceptible to TMEV-induced demyelination. Conversely, BALB/c astrocytes, derived from animals genetically resistant to demyelination, did not produce IL-1 alpha in detectable amounts. Therefore, a differential IL-1 gene expression, which is strain specific, is demonstrated after TMEV infection in astrocytes. The release of IL-1 alpha by SJL astrocytes was studied from kinetic, infectivity, and immunochemical points of view. Since IL-1 plays a critical role in the immune response, its production by astrocytes in some strains of mice may contribute to virus-induced susceptibility and to inflammation associated with this experimental model of multiple sclerosis.

  5. 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.

  6. 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

  7. 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

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

    2015-06-01

    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.

  8. Susceptibility and resistance of inbred mice to Paracoccidioides brasiliensis.

    PubMed Central

    Calich, V. L.; Singer-Vermes, L. M.; Siqueira, A. M.; Burger, E.

    1985-01-01

    Nine different inbred strains of mice inoculated intraperitoneally with yeast cells of Paracoccidioides brasiliensis showed significantly varying patterns of susceptibility. The A/SN strain was found to be the most resistant, while BIOD2/nSn, BIO.A and BIOD2/oSn the most susceptible strains. These susceptibility differences were not dependent on the size of challenge inocula and sex of animals. All strains studied showed a mean survival time proportional to the size of inocula used. Although almost all infected male mice presented a shorter survival time when compared with females, significant mortality differences between sexes were found only in two of the strains studied, namely BALB/c and BIOD2/nSn. The H-2 region did not influence the susceptibility pattern since the A/SN and BIO.A strains share the same H-2 haplotype and were respectively highly resistant and susceptible to P. brasiliensis. Furthermore, the presence of C5 and unresponsiveness to lipopolysaccharide had no influence on the mortality data observed. Specific antibodies were detected only in a small number of animals and titres were consistently low, appearing later in the resistant (A/SN) than in a susceptible strain (BIO.A). Omentum, spleen and liver were the most affected organs in both strains, but the susceptible mice had more granulomatous lesions and earlier dissemination of the fungus. PMID:4063162

  9. 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

  10. 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.

  11. 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. PMID:27630762

  12. 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.

  13. [Carbapenem-resistant Acinetobacter baumannii strains].

    PubMed

    Bogiel, Tomasz; Kwiecińska-Piróg, Joanna; Jachna-Sawicka, Katarzyna; Gospodarek, Eugenia

    2010-01-01

    A. baumannii rods are opportunistic pathogens responsible generally for nosocomial infections. Resistance to carbapenems, observed among them, is a serious threat due to ability to be transmitted between bacterial species. The aim of our study was to evaluate the frequency of isolation and susceptibility to antibiotics of resistant to imipenem and/or meropenem A. baumannii strains isolated between 2007 and 2009 from patients of University Hospital of dr A. Jurasz Collegium Medicum of L. Rydygier in Bydgoszcz Nicolaus Copernicus University in Toruń. Study shows increasing frequency of isolation that type of strains from 4 in 2007 to 95 in 2008 and 67 in 2009. Percentage of imipenem-resistant isolates raised to 27.6% in 2008 and 31.0% in 2009. Meropenem-resistant A. baumannii isolates frequency changed from 2.1% in 2007 to 31.2% and 34.6%, in 2008 and 2009, respectively. The majority of strains were obtained from patients of the Intensive Care Units and surgery clinics. Examined A. baumannii strains were generally isolated from bronchoalveolar lavage (25.3%) and wound (18.1%) or throat (12.0%) swabs samples. The isolates demonstrated full resistance to norfloxacin, ciprofloxacin, and chloramphenicol. Ampicillin/sulbactam (24.8%), tobramycin (8.1%) and colistin (1.5%) presented the highest in vitro activity against isolated strains.

  14. [Vancomycin-resistant Enterococcus spp. strains].

    PubMed

    Kozuszko, Sylwia; Bogiel, Tomasz; Gospodarek, Eugenia

    2009-01-01

    The aim of our study was to evaluate a frequency of isolation and susceptibility to antibiotics of vancomycin-resistant enterococci isolated between 2005 and the first half of the 2009 from patients of University Hospital of Dr. A. Jurasz Collegium Medicum of L. Rydygier in Bydgoszcz Nicolaus Copernicus University in Toruli. Study shows increasing frequency of VRE isolation from two in 2005, 8 in 2006, 30 in 2007 to 79 in 2008 and 40 in the first half of 2009 year. Among all isolated VRE strains E. faecium definitely predominated (75.0-90.0% in 2006-2009). The majority of strains were obtained from patients of the Pediatrics, Hematology and Oncology Clinic (43,4%) and Pediatric Surgery Clinic (41.5%). VRE strains were mainly isolated from digestive tract (79,9%). The isolates demonstrated frequently resistance to penicillin, ampicillin, ciprofloxacin, rifampicin and chloramphenicol. Percentage of VRE strain resistant to aminoglycosides decreased during the last four years of study. Over 56% of VRE isolates showed resistance to teicoplanin. Linezolid and quinupristin-dalfopristin were the only drugs presenting activity against isolated VRE strains.

  15. 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.

  16. 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

  17. 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

  18. Enterotoxigenicity of aeromonas strains in suckling mice.

    PubMed

    Jánossy, G; Tarján, V

    1980-01-01

    The enterotoxigenicity of 170 Aeromonas strains isolated from different sources (food poisoning, random food sampling, water, faeces) was examined by the suckling mouse test. The strains were grown on Syncaye culture medium covered with sterilized membrane for Kiil-kidney. The culture supernatants were inoculated orally. Ileal loop dilatation was compared to that produced by the international standard enterotoxic Escherichia coli B7A (O148 : H28) and B2C (O6 : H16) strains. Of the 87 Aeromonas hydrophila strains 69, of the 76 Aeromonas punctate subsp. caviae strains 9, the 6 Aeromonas punctata subsp. punctata strains 5, and 1 Aeromonas salmonicida subsp. achromogenes gave a positive reaction in the test.

  19. 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.

  20. Evaluation of Vancoplus versus ceftriaxone against cephalosporin resistance MRSA strain in experimental meningitis model.

    PubMed

    Soni, A; Chaudhary, M; Dwivedi, V K; Kumar, S; Shrivastava, S M

    2010-06-01

    The aim of this study was to compare the efficacy of ceftriaxone plus vancomycin (Vancoplus) versus ceftriaxone alone against cephalosporin resistant methicillin-resistant Staphylococcus aureus (MRSA) strain by using meningitis mice model. The MRSA strain ATCC 43300 was used to induce meningitis in mice. The mice were fed standard pelleted diet and water ad libitum. The test room was air conditioned with temperature 23 +/- 2 degrees C, humidity 65+/- 5% and with artificial fluorescent light 10-14 hrs. of light and dark, respectively. Twenty four mice were divided into four group containing six rats in each group. The ceftriaxone group received 28.57 mg/Kg body weight/day and the vancoplus group received 42.8 mg/Kg body weight/day and control as well as infected group received normal saline. The bacterial susceptibility test in CSF was performed for cephalosporin resistance MRSA strain by determining the lytic zone for the vancoplus and ceftriaxone antibiotic. The lytic zone was more in vancoplus as compared to ceftriaxone. It was also found that activities of antioxidant enzymes such as catalase were significantly increased (p<0.001) along with decreased (p<0.001) in lipid peroxidation (malonaldialdehyde) level in CSF of vancoplus treated group as compared to infected as well as ceftriaxone resistance group and come back to normal level. It was concluded that vancoplus beneficial for the patients who suffered from cephalosporin resistant MRSA bacterial strain.

  1. Diet-induced obese mice develop peripheral, but not central, resistance to leptin.

    PubMed Central

    Van Heek, M; Compton, D S; France, C F; Tedesco, R P; Fawzi, A B; Graziano, M P; Sybertz, E J; Strader, C D; Davis, H R

    1997-01-01

    Leptin administration reduces obesity in leptin-deficient ob/ob mice; its effects in obese humans, who have high circulating leptin levels, remain to be determined. This longitudinal study was designed to determine whether diet-induced obesity in mice produces resistance to peripheral and/or central leptin treatment. Obesity was induced in two strains of mice by exposure to a 45% fat diet. Serum leptin increased in proportion to body weight (P < 0.00001). Whereas C57BL/6 mice initially responded to peripherally administered leptin with a marked decrease in food intake, leptin resistance developed after 16 d on high fat diet; mice on 10% fat diet retained leptin sensitivity. In AKR mice, peripheral leptin significantly decreased food intake in both 10 and 45% fat-fed mice after 16 d of dietary treatment. However, after 56 d, both groups became resistant to peripherally administered leptin. Central administration of leptin to peripherally leptin-resistant AKR mice on 45% fat diet resulted in a robust response to leptin, with a dose-dependent decrease in food intake (P < 0.00001) and body weight (P < 0.0001) after a single intracerebroventricular infusion. These data demonstrate that, in a diet-induced obesity model, mice exhibit resistance to peripherally administered leptin, while retaining sensitivity to centrally administered leptin. PMID:9022070

  2. 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

  3. Immunopathology of mouse hepatitis virus type 3mii. effect of immunosuppression in resistant mice.

    PubMed

    Dupuy, J M; Levey-Leblond, E; Le Prevost, C

    1975-01-01

    Normal adult A strain mice are resistant to MHV-3 infection. A strain mice immunosuppressed by 600 rads of x-irradiation or by anti-lymphocyte serum treatment became susceptible to the virus and died with specific lesions of the liver and high virus titers. However, mice immunized with MHV-3 before sublethal x-iraddiation resisted a second injection of virus. Resistant adult (A times C3H) F-1 hybrids undergoing graft-vs-host (GVH) reaction became highly susceptible to MHV-3 injected 8 days after parental cell injection. Virus titer 3 days after injection was 2 logs higher in mice undergoing GVH than in controls. However F-1 hybrid mice resisted virus challenge when the first injection of virus was given 2 weeks before GVH induction. In addition, thymectomy also modified the behavior of resistant animals toward virus infection. It appears, therefore, that cell-mediated immune functions play an important role in resistance of mice to MHV-3.

  4. Within-strain variation in behavior differs consistently between common inbred strains of mice.

    PubMed

    Loos, Maarten; Koopmans, Bastijn; Aarts, Emmeke; Maroteaux, Gregoire; van der Sluis, Sophie; Verhage, Matthijs; Smit, August B

    2015-08-01

    Genetic and environmental factors interact throughout life and give rise to individual differences, i.e., individuality. The diversifying effect of environmental factors is counteracted by genetic mechanisms to yield persistence of specific features (robustness). Here, we compared robustness between cohorts of isogenic mice of eight different commonly used strains by analyzing to what extent environmental variation contributed to individuality in each of the eight genotypes, using a previously published dataset. Behavior was assessed in the home-cage, providing control over environmental factors, to reveal within-strain variability in numerous spontaneous behaviors. Indeed, despite standardization and in line with previous studies, substantial variability among mice of the same inbred strain was observed. Strikingly, across a multidimensional set of 115 behavioral parameters, several strains consistently ranked high in within-strain variability (DBA/2J, 129S1/Sv A/J and NOD/LtJ), whereas other strains ranked low (C57BL/6J and BALB/c). Strain rankings of within-strain variability in behavior were confirmed in an independent, previously published behavioral dataset using conventional behavioral tests administered to different mice from the same breeding colonies. Together, these show that genetically inbred mouse strains consistently differ in phenotypic robustness against environmental variation, suggesting that genetic factors contribute to variation in robustness. PMID:26123533

  5. Linezolid susceptibility in Helicobacter pylori, including strains with multidrug resistance.

    PubMed

    Boyanova, Lyudmila; Evstatiev, Ivailo; Gergova, Galina; Yaneva, Penka; Mitov, Ivan

    2015-12-01

    Only a few studies have evaluated Helicobacter pylori susceptibility to linezolid. The aim of the present study was to assess linezolid susceptibility in H. pylori, including strains with double/multidrug resistance. The susceptibility of 53 H. pylori strains was evaluated by Etest and a breakpoint susceptibility testing method. Helicobacter pylori resistance rates were as follows: amoxicillin, 1.9%; metronidazole, 37.7%; clarithromycin, 17.0%; tetracycline, 1.9%; levofloxacin, 24.5%; and linezolid (>4 mg/L), 39.6%. The linezolid MIC50 value was 31.2-fold higher than that of clarithromycin and 10.5-fold higher than that of levofloxacin; however, 4 of 11 strains with double/multidrug resistance were linezolid-susceptible. The MIC range of the oxazolidinone agent was larger (0.125-64 mg/L) compared with those in the previous two reports. The linezolid resistance rate was 2.2-fold higher in metronidazole-resistant strains and in strains resistant to at least one antibiotic compared with the remaining strains. Briefly, linezolid was less active against H. pylori compared with clarithromycin and levofloxacin, and linezolid resistance was linked to resistance to metronidazole as well as to resistance to at least one antibiotic. However, linezolid activity against some strains with double/multidrug resistance may render the agent appropriate to treat some associated H. pylori infections following in vitro susceptibility testing of the strains. Clinical trials are required to confirm this suggestion.

  6. The correlation of virulence, pathogenicity, and itraconazole resistance with SAP activity in Candida albicans strains.

    PubMed

    Feng, Wenli; Yang, Jing; Pan, Yanwei; Xi, Zhiqin; Qiao, Zusha; Ma, Yan

    2016-02-01

    The relationship between SAP2 activity and drug resistance in Candida albicans was investigated by using itraconazole-resistant and itraconazole-sensitive C. albicans isolates. The precipitation zones were measured to analyze SAP2 activity. Mice were classified into itraconazole-resistant and -sensitive C. albicans isolate groups, and a control group, with their survival and mortality rate being observed over 30 days. The relative expression levels of CDR1, CDR2, MDR1, and SAP2 were measured using RT-PCR. It was found that the secreted aspartyl proteinase activity of itraconazole-resistant C. albicans strains was significantly higher than that of itraconazole-sensitive C. albicans strains (P < 0.001). A significantly higher mortality rate was recorded for mice treated with itraconazole-resistant C. albicans than for mice treated with itraconazole-sensitive C. albicans. In regards to the CDR1, CDR2, and MDR1 genes, there was no significant difference between the 2 groups of mice. Positive correlations between SAP2 and MDR1 and between CDR1 and CDR2 were found. The high expression level of SAP2 may relate to the virulence, pathogenicity, and resistance of C. albicans.

  7. 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...

  8. Aminoglycoside resistance patterns of Serratia marcescens strains of clinical origin.

    PubMed Central

    Coria-Jiménez, R.; Ortiz-Torres, C.

    1994-01-01

    Aminoglycoside resistance patterns of 147 Serratia marcescens strains of clinical origin were studied. All strains analysed belonged to three different bacterial populations. The periods of study and the institutions the strains were isolated from correlated significantly with the resistance patterns shown by the strains. The most frequent resistance patterns found were the following: ACC (6')-I at the Hospital Infantil de México (Children's Hospital of México), and ANT (2'') + AAC(6')-I at the Instituto Nacional de Pediatría (INPed or National Institute of Pediatrics) in Mexico City. Furthermore, the isolation frequency of aminoglycoside-sensitive strains decreased remarkably at the INPed over a 12-year period. These results suggest that there has been a selection of Serratia marcescens strains that are very resistant to aminoglycosides. PMID:8119351

  9. [Drug resistance in nosocomial strains of staphylococci to methicillin].

    PubMed

    Sawicka-Grzelak, A; Rokosz, A; Meisel-Mikołajczyk, F

    1998-01-01

    The aim of the present study was the analysis of drug susceptibility of MRSA and MRCNS strains isolated from patients hospitalized in 14 wards of the State Clinical Hospital No 1 in Warsaw. The strains were identified (ID 32 STAPH), and their susceptibility to antimicrobial agents (ATB STAPH) was determined in ATB system (bioMérieux, France). Four methods were applied to confirm the resistance to methicillin: ATB-plus system, disc-diffusion method (Oxa 1 microgram, Oxoid, U.K.), Crystal MRSA ID (Becton Dickinson-BBL, USA) and agar screen test in TSA medium (Difco, USA) with methicillin (25 mg/l, Sigma, USA). 108 Staphylococcus spp. strains were found in 300 clinical specimens. 56 strains were methicillin-resistant (52%). Among methicillin-resistant strains 13 MRSA, 28 MRSE and 15 of other species were found. All MRSA strains were susceptible to vancomycin, teicoplanin and fusidic acid. MRCNS were susceptible first of all to vancomycin (43/43), minocycline (42/43) and pristinamycin (42/43). On the basis of the obtained results it can be stated that methicillin-resistant staphylococci occur in hospital wards. The greatest number of methicillin-resistant strains was cultured from patients hospitalized in surgery wards (32), methicillin-resistant strains much more frequently occur among coagulase-negative staphylococci, especially in Staphylococcus epidermis. Glycopeptide antibiotics are most active against isolated MRSA strains. The most active therapeutic agent against MRCNS is vancomycin. PMID:9857608

  10. [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

  11. Resistance to mycoplasmal lung disease in mice is a complex genetic trait.

    PubMed Central

    Cartner, S C; Simecka, J W; Briles, D E; Cassell, G H; Lindsey, J R

    1996-01-01

    Mouse strains differ markedly in resistance to Mycoplasma pulmonis infection, and investigation of these differences holds much promise for understanding the mechanisms of antimycoplasmal host defenses. To determine the potential genetic diversity of resistance to disease in murine respiratory mycoplasmosis (MRM) and to select disease-resistant and nonresistant mouse strains for further genetic analysis, we screened 17 inbred mouse strains of various Bcg and H-2 genotypes for resistance to M. pulmonis. Mice were inoculated intranasally with 10(4) CFU of M. pulmonis UAB CT and evaluated at 21 days postinfection for severities of the four histologic lung lesions characteristic of MRM: alveolar exudate, airway exudate, airway epithelial hyperplasia, and lymphoid infiltrate. On the basis of these assessments of MRM severity, one group of mouse strains was found to be extremely resistant to disease (C57BR/cdJ, C57BL/6NCr, C57BL/10ScNCr, and C57BL/6J). The remaining strains of mice (C57L/J, SJL/NCr, BALB/cAnNCr, A/JCr, C3H/HeJ, SWR/J, AKR/NCr, CBA/NCr, C58/J, DBA/2NCr, C3H/HeNCr, C3HeB/FeJ, and C3H/HeJCr) developed disease of widely varying severities. Furthermore, strains in the group with more disease varied in pattern of lesion severity. While the severities of all four lesions were correlated in most mouse strains, this was not always true. DBA/2NCr mice had one of the highest scores for alveolar exudate, only a moderate score for airway exudate, and significantly lower scores for both airway epithelial hyperplasia and lymphoid infiltrate than all other strains susceptible to lung disease. DBA/2NCr mice had one of the highest mortality rates. We concluded that resistance to MRM is a complex trait. The observed differences in lung disease severity could not be explained by known differences at the Bcg or H-2 locus in the strains of mice we studied. PMID:8945584

  12. Differential zinc transport into testis and brain of cadmium-sensitive and -resistant murine strains.

    PubMed

    King, L M; Banks, W A; George, W J

    2000-01-01

    Recently, we showed that murine strain differences to the testicular toxicity of cadmium (Cd) are the result of variable transport of Cd across the blood-testis barrier. Because Cd is a nonessential trace element, it must be using the transporter for an endogenous substance. The objectives for this study were to determine the natural ligand for the transport system used by Cd to enter testis and brain, and to determine whether the transport of that natural ligand also differs among Cd-sensitive and -resistant murine strains. Because zinc (Zn) and Cd are cations of similar size and charge, and because Cd has been shown to inhibit Zn uptake in a variety of systems, we hypothesized that Cd was using Zn transporters to enter tissues. In this study we characterized Zn transport into the testis and brain of Cd-sensitive and -resistant murine strains. We found that the transport of 65Zn into testis and brain of Cd-resistant A/J mice was significantly reduced compared with that in Cd-sensitive 129/J mice. In 129/J mice, unlabeled CdCl2 significantly reduced 65Zn transport by 56% in testes and by 47% in brain. Pretreatment with Zn had no significant effect on 109Cd transport rates into testes or brain of 129/J or A/J mice, but did reduce the percentage of the injected 109Cd dose in testes of 129/J mice by 44% within 60 minutes. From these results we can conclude that Cd is using transport systems that normally function to regulate Zn levels in testes and brain. Murine strain resistance to the testicular effects of Cd is associated with a concomitant attenuation of the Zn transport system in testis.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Establishment of latent herpes simplex virus type 1 infection in resistant, sensitive, and immunodeficient mouse strains.

    PubMed

    Ellison, A R; Yang, L; Voytek, C; Margolis, T P

    2000-03-01

    Productive infection with herpes simplex virus (HSV) type 1 is limited by both innate and adaptive immune mechanisms. The purpose of the current study was to determine whether these mechanisms also play a role in the establishment of latent HSV infection. First we examined the trigeminal ganglia (TG) of severe combined immunodeficiency (SCID), interferon-gamma knockout (GKO), and beige (a strain deficient in natural killer cell activity) mice following ocular inoculation with HSV. Although infection of SCID mice was invariably lethal, we consistently found latently infected neurons in the TG of these animals at 2-4 days postinoculation. HSV infection of GKO and beige mice, while not lethal, was characterized by a greater number of productively infected TG neurons and/or a delay in the time to peak productive infection compared to C57BL/6 controls. However, as assayed by both in situ hybridization for LAT expression and quantitative PCR (Q-PCR) for viral DNA, we found that HSV established a latent infection in GKO and beige mice as efficiently as in C57BL/6 controls. We subsequently examined the TG of "HSV-sensitive" strains of mice (Swiss-Webster, CBA, and BALB/c) following ocular infection with HSV. At the peak of acute ganglionic infection the number of productively infected TG neurons in each of these mouse strains was about sevenfold greater than in the "HSV-resistant" strain C57BL/6, consistent with previously reported differences in susceptibility to lethal challenge with HSV. However, as assayed by both in situ hybridization for LAT and Q-PCR for viral DNA, we found that HSV established a latent infection in Swiss-Webster, CBA, and BALB/c mice as efficiently as in C57BL/6 controls. We conclude that HSV efficiently establishes latent infection in the TG of mice in the absence of innate and adaptive immune mechanisms that are essential for limiting productive viral infection.

  6. RB virus: a strain of Friend virus that produces a 'Friend virus-like' disease in Fv-2rr mice.

    PubMed

    Geib, R W; Seaward, M B; Stevens, M L; Cho, C L; Majumdar, M

    1989-10-01

    RB virus is a newly derived strain of Friend virus that was adapted to produce a 'Friend-like' disease in mice that are genetically resistant to wild-type Friend virus. RB virus was produced by passing high titers of the wild-type Friend virus (Lilly-Steeves polycythemia-producing strain) through adult Fv-2rr mice. Titration of the defective spleen focus-forming virus indicated RB virus infected similar numbers of Fv-2ss or Fv-2rr target cells. Analysis of the spleens from mice infected with RB virus indicated that RB induced the early stage of Friend disease (erythroid proliferation) in both Fv-2rr and Fv-2ss mice. Fv-2ss mice infected with RB virus developed the classical Friend disease within 3 weeks. In contrast, the percentage of Fv-2rr mice developing the 'Friend-like' disease after infection with RB virus never exceeded 60%. The latency period of RBV in Fv-2rr mice was strain dependent. D2.R16 (Fv-2rr) developed the syndrome more rapidly than C57BL/6 (Fv-2rr). RB virus retained the capacity to transform erythroprogenitor cells from both Fv-2ss and Fv-2rr animals. Cells infected with RB virus consistently produced a modified SFFV envelope protein, gp48.

  7. Serum Resistance in an Invasive, Nontypeable Haemophilus influenzae Strain

    PubMed Central

    Williams, Bryan J.; Morlin, Gregory; Valentine, Nathan; Smith, Arnold L.

    2001-01-01

    A common feature of many different organisms causing bacteremia is the ability to avoid the bactericidal effects of normal human serum. In Haemophilus influenzae encapsulated strains are particularly serum resistant; however, we found that a nonencapsulated strain (R2866) isolated from the blood of an immunocompetent child with meningitis who had been successfully immunized with H. influenzae type b conjugate vaccine was serum resistant. Since serum resistance usually involves circumventing the action of the complement system, we defined the deposition of various complement components on the surfaces of this H. influenzae strain (R2866), a nonencapsulated avirulent laboratory strain (Rd), and a virulent type b encapsulated strain (Eagan). Membrane attack complex (MAC) accumulation correlated with the loss of bacterial viability; correspondingly, the rates of MAC deposition on the serum-sensitive strain Rd and the serum-resistant strains differed. Analysis of cell-associated immunoglobulin G (IgG), C1q, C3b, and C5b indicated that serum-resistant H. influenzae prevents MAC accumulation by delaying the synthesis of C3b through the classical pathway. Among the initiators of the classical pathway, IgG deposition contributes most of the C3 convertase activity necessary to start the cascade ending with MAC deposition. Despite similar IgG binding, strain R2866 delays C3 convertase activity compared to strain Rd. We conclude that strain R2866 can persist in the bloodstream, in part by inhibiting or delaying C3 deposition on the cell surface, escaping complement mediated killing. PMID:11159957

  8. Expression of methicillin resistance in heterogeneous strains of Staphylococcus aureus.

    PubMed Central

    Hartman, B J; Tomasz, A

    1986-01-01

    The phenotypic expression of methicillin resistance was studied in a number of clinical isolates and laboratory strains of Staphylococcus aureus. The methicillin-resistant S. aureus strains could be divided into three classes, homogeneous, heterogeneous, and thermosensitive heterogeneous methicillin-resistant S. aureus, on the basis of their plating efficiencies at 30 or 37 degrees C on methicillin-containing agar plates. Heterogeneous strains of methicillin-resistant S. aureus were composed of two subpopulations: a small minority of cells (10(-5) to 10(-3); MIC, 600 to 1,000 micrograms/ml) that expressed resistance to high concentrations of methicillin at 37 degrees C, and a majority of cells (MIC, 5 micrograms/ml) that remained susceptible to the drug at 37 degrees C. Cultures of a thermosensitive heterogeneous strain were able to grow in the presence of high concentrations of methicillin, provided that the growth temperature was 30 degrees C. Such cultures lost their phenotypic resistance within 30 min (i.e., in less than one doubling time) after the growth temperature was shifted to the nonpermissive 37 degrees C. Shift of the temperature of the culture in the reverse direction (37 to 30 degrees C) resulted in an equally rapid expression of phenotypic resistance. The majority of the cells in such heterogeneous strains may be considered heat (or salt) conditional in their phenotypic expression of methicillin resistance. Both heterogeneous and thermosensitive heterogeneous strains, irrespective of their temperature of cultivation and degree of phenotypic resistance, contained detectable quantities of the 78-kilodalton penicillin-binding protein 2a (PBP 2a) that previous studies have suggested is a biochemical correlate of methicillin resistance in homogeneous strains of methicillin-resistant S. aureus. However, in contrast to the homogeneous stains, in heterogeneous and thermosensitive heterogeneous isolates the ability to synthesize PBP 2a is apparently not

  9. Selection and characterization of cyanophage resistance in marine Synechococcus strains.

    PubMed

    Stoddard, Lauren I; Martiny, Jennifer B H; Marston, Marcia F

    2007-09-01

    Marine viruses are an important component of the microbial food web, influencing microbial diversity and contributing to bacterial mortality rates. Resistance to cooccurring cyanophages has been reported for natural communities of Synechococcus spp.; however, little is known about the nature of this resistance. This study examined the patterns of infectivity among cyanophage isolates and unicellular marine cyanobacteria (Synechococcus spp.). We selected for phage-resistant Synechococcus mutants, examined the mechanisms of phage resistance, and determined the extent of cross-resistance to other phages. Four strains of Synechococcus spp. (WH7803, WH8018, WH8012, and WH8101) and 32 previously isolated cyanomyophages were used to select for phage resistance. Phage-resistant Synechococcus mutants were recovered from 50 of the 101 susceptible phage-host pairs, and 23 of these strains were further characterized. Adsorption kinetic assays indicate that resistance is likely due to changes in host receptor sites that limit viral attachment. Our results also suggest that receptor mutations conferring this resistance are diverse. Nevertheless, selection for resistance to one phage frequently resulted in cross-resistance to other phages. On average, phage-resistant Synechococcus strains became resistant to eight other cyanophages; however, there was no significant correlation between the genetic similarity of the phages (based on g20 sequences) and cross-resistance. Likewise, host Synechococcus DNA-dependent RNA polymerase (rpoC1) genotypes could not be used to predict sensitivities to phages. The potential for the rapid evolution of multiple phage resistance may influence the population dynamics and diversity of both Synechococcus and cyanophages in marine waters.

  10. Effect of severe calorie restriction on the lung in two strains of mice

    PubMed Central

    Bishai, John M.; Mitzner, Wayne

    2008-01-01

    There is a body of literature in animal models that has suggested the development of emphysema following severe calorie restriction. This has led to the notion of “nutritional emphysema” that might have relevance in COPD patients. There have been few studies, however, that have looked closely at both the mechanics and lung structure in the same animals. In the present work, we examined lung mechanics and histological changes in two strains of mice that have substantial differences in alveolar size, the C57BL/6 and C3H/HeJ strains. We quantified the dynamic elastance and resistance at 2.5 Hz, the quasistatic pressure volume curve, and the alveolar chord lengths in lungs inflated to a lung capacity at 25–30 cmH2O. We found that after 2 or 3 wk of calorie restriction to 1/3 their normal diet, the lungs became stiffer with increased resistance. In addition, the lung capacity was also decreased. These mechanical changes were reversed after 2 wk on a normal ad libitum diet. Histology of the postmortem fixed lungs showed no changes in the mean alveolar chord lengths with calorie restriction. Although the baseline mechanics and alveolar size were quantitatively different in the two strains, both strains showed similar qualitative changes during the starvation and refeeding periods. Thus, in two strains of mice with genetically determined differences in alveolar size, neither the mechanics nor the histology show any evidence of emphysema-like changes with this severe caloric insult. PMID:18515406

  11. Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains.

    PubMed

    Anh, Dao Bui Tran; Faisca, Pedro; Desmecht, Daniel J-M

    2006-09-01

    Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 yr of age. It is assumed that host factors influence the severity of the disease presentation and thus the need for hospitalization. As a first step toward the identification of the underlying genes involved, this study was undertaken to establish whether inbred mouse strains differ in susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV, which has been shown to accurately mimic the RSV disease of children. With this purpose in mind, double-chamber plethysmography and carbon monoxide uptake data were collected daily for 7 days after inoculation of PVM in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values reflected the success of viral replication in the lungs and revealed a pattern of continuous variation, with resistant, intermediate, and susceptible strains. The results suggest that SJL (resistant) and 129/Sv (susceptible) strains should be used in crossing experiments aimed at identifying genes controlling pneumovirus replication by the positional cloning approach. Similarly, crossing experiments using BALB/c or C57BL/6 (resistant) and DBA/2 or 129/Sv (susceptible) will allow the identification of the genes involved in the control of pulmonary inflammation during pneumovirus infection.

  12. [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

  13. 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.

  14. Comparison of immune responses and resistance to brucellosis in mice vaccinated with Brucella abortus 19 or RB51.

    PubMed

    Stevens, M G; Olsen, S C; Pugh, G W; Brees, D

    1995-01-01

    Immune responses and resistance to infection with Brucella abortus 2308 (S2308) were measured in mice following vaccination with B. abortus 19 (S19) or the lipopolysaccharide (LPS) O-antigen-deficient mutant, strain RB51 (SRB51). Live bacteria persisted for 8 weeks in spleens of mice vaccinated with 5 x 10(6) or 5 x 10(8) CFU of SRB51, whereas bacteria persisted for 12 weeks in mice vaccinated with 5 x 10(6) CFU of S19. Mice vaccinated with 5 x 10(6) or 5 x 10(8) CFU of SRB51 had increased resistance to infection with S2308 at 12, 16, and 20 weeks after vaccination, but the resistance was lower than that induced by vaccinating mice with 5 x 10(6) CFU of S19. Spleen cells obtained from mice vaccinated with S19 or SRB51 generally exhibited similar proliferative responses to S2308 bacteria or bacterial proteins (106 to 18 kDa) following challenge of mice with S2308 at 12, 16, or 20 weeks after vaccination. Mice vaccinated with S19 had antibody to S2308 bacteria and S2308 smooth LPS at 4, 8, and 12 weeks after vaccination. In contrast, mice vaccinated with either dose of SRB51 did not produce antibody to S2308 smooth LPS. In addition, only mice vaccinated with the highest dose of SRB51 (5 x 10(8) CFU) had antibody responses to S2308 bacteria, although the responses were lower and less persistent than those in mice vaccinated with S19. Collectively, these results indicate that SRB51-vaccinated mice have similar cell-mediated immune responses to S2308 but lower resistance to infection with S2308 compared with S19-vaccinated mice. The lower resistance in SRB51-vaccinated mice probably resulted from a combination of rapid clearance of SRB51 and an absence of antibodies to S2308 LPS.

  15. Phenotypic variation of fluoride responses between inbred strains of mice.

    PubMed

    Yan, Dong; Willett, Thomas L; Gu, Xiao-Mei; Martinez-Mier, E Angeles; Sardone, Laura; McShane, Lauren; Grynpas, Marc; Everett, Eric T

    2011-01-01

    Excessive systemic exposure to fluoride (F) can lead to disturbances in bone homeostasis and dental enamel development. We have previously shown strain-specific responses to F in the development of dental fluorosis (DF) and in bone formation/mineralization. The current study was undertaken to further investigate F responsive variations in bone metabolism and to determine possible relationships with DF susceptibility. Seven-week-old male mice from FVB/NJ, C57BL/6J, C3H/HeJ, A/J, 129S1/SvImJ, AKR/J, DBA/2J, and BALB/cByJ inbred strains were exposed to NaF (0 or 50 ppm as F(-)) in drinking water for 60 days. Sera were collected for F, Ca, Mg, PO(4), iPTH, sRANKL, and ALP levels. Bone marrow cells were subjected to ex vivo cell culture for osteoclast potential and CFU colony assays (CFU-fibroblast, CFU-osteoblast, CFU-erythrocyte/granulocyte/macrophage/megakaryocyte, CFU-granulocyte/macrophage, CFU-macrophage, and CFU-granulocyte). Femurs and vertebrae were subjected to micro-CT analyses, biomechanical testing, and F, Mg, and Ca content assays. DF was evaluated using quantitative fluorescence and clinical criteria. Strain-specific responses to F were observed for DF, serum studies, ex vivo cell culture studies, and bone quality. Among the strains, there were no patterns or significant correlations between DF severity and the actions of F on bone homeostasis (serum studies, ex vivo assays, or bone quality parameters). The genetic background continues to play a role in the actions of F on tooth enamel development and bone homeostasis. F exposure led to variable phenotypic responses between strains involving dental enamel development and bone metabolism.

  16. Phenotypic Variation of Fluoride Responses between Inbred Strains of Mice

    PubMed Central

    Yan, Dong; Willett, Thomas L.; Gu, Xiao-Mei; Martinez-Mier, E. Angeles; Sardone, Laura; McShane, Lauren; Grynpas, Marc; Everett, Eric T.

    2011-01-01

    Excessive systemic exposure to fluoride (F) can lead to disturbances in bone homeostasis and dental enamel development. We have previously shown strain-specific responses to F in the development of dental fluorosis (DF) and in bone formation/mineralization. The current study was undertaken to further investigate F responsive variations in bone metabolism and to determine possible relationships with DF susceptibility. Seven-week-old male mice from FVB/NJ, C57BL/6J, C3H/HeJ, A/J, 129S1/SvImJ, AKR/J, DBA/2J, and BALB/cByJ inbred strains were exposed to NaF (0 or 50 ppm as F–) in drinking water for 60 days. Sera were collected for F, Ca, Mg, PO4, iPTH, sRANKL, and ALP levels. Bone marrow cells were subjected to ex vivo cell culture for osteoclast potential and CFU colony assays (CFU-fibroblast, CFU-osteoblast, CFU-erythrocyte/granulocyte/macrophage/megakaryocyte, CFU-granulocyte/macrophage, CFU-macrophage, and CFU-granulocyte). Femurs and vertebrae were subjected to micro-CT analyses, biomechanical testing, and F, Mg, and Ca content assays. DF was evaluated using quantitative fluorescence and clinical criteria. Strain-specific responses to F were observed for DF, serum studies, ex vivo cell culture studies, and bone quality. Among the strains, there were no patterns or significant correlations between DF severity and the actions of F on bone homeostasis (serum studies, ex vivo assays, or bone quality parameters). The genetic background continues to play a role in the actions of F on tooth enamel development and bone homeostasis. F exposure led to variable phenotypic responses between strains involving dental enamel development and bone metabolism. PMID:21555858

  17. 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

  18. Identification and Characterization of Vancomycin-resistant Enterococcus species Frequently Isolated from Laboratory Mice

    PubMed Central

    Yamanaka, Hitoki; Takagi, Toshikazu; Ohsawa, Makiko; Yamamoto, Naoto; Kubo, Noriaki; Takemoto, Takahira; Sasano, Shoko; Masuyama, Ritsuko; Ohsawa, Kazutaka

    2014-01-01

    To determine the prevalence of drug resistant bacteria colonizing laboratory mice, we isolated and characterized vancomycin-resistant Enterococcus species (VRE) from commercially available mice. A total of 24 VRE isolates were obtained from 19 of 21 mouse strains supplied by 4 commercial breeding companies. Of these, 19 isolates of E. gallinarum and 5 isolates of E. casseliflavus possessing the vanC1 and vanC2/3 genes intrinsically, exhibited intermediate resistance to vancomycin respectively. In addition, these isolates also exhibited diverse resistant patterns to erythromycin, tetracycline, and ciprofloxacin, whereas the use of antibiotics had not been undertaken in mouse strains tested in this study. Although 6 virulence-associated genes (ace, asa, cylA, efaA, esp, and gelE) and secretion of gelatinase and hemolysin were not detected in all isolates, 23 of 24 isolates including the isolates of E. casselifalvus secreted ATP into culture supernatants. Since secretion of ATP by bacteria resident in the intestinal tract modulates the local immune responses, the prevalence of ATP-secreting VRE in mice therefore needs to be considered in animal experiments that alter the gut microflora by use of antibiotics. PMID:25077759

  19. Gastrointestinal Colonization by Candida albicans Mutant Strains in Antibiotic-Treated Mice

    PubMed Central

    Wiesner, Stephen M.; Jechorek, Robert P.; Garni, Robb M.; Bendel, Catherine M.; Wells, Carol L.

    2001-01-01

    Antibiotic-treated mice orally inoculated with one of three Candida albicans strains (including two mutant strains) or indigenous Candida pelliculosa showed levels of candidal gastrointestinal colonization that were strain specific. However, regardless of strain, the numbers of viable candida were intermediate to high in the stomach, were consistently lowest in the upper small intestine, and increased progressively down the intestinal tract. PMID:11139219

  20. Antiherpetic properties of acyclovir 5'-hydrogenphosphonate and the mutation analysis of herpes virus resistant strains.

    PubMed

    Gus'kova, Anna A; Skoblov, Mikhail Yu; Korovina, Anna N; Yasko, Maxim V; Karpenko, Inna L; Kukhanova, Marina K; Andronova, Valeria L; Galegov, George A; Skoblov, Yuri S

    2009-10-01

    In this study, we continued to study antiherpetic properties of acyclovir 5'-hydrogenphosphonate (Hp-ACV) in cell cultures and animal models. Hp-ACV was shown to inhibit the development of herpetic infection in mice induced by the HSV-1/L(2) strain. The compound suppressed replication of both ACV-sensitive HSV-1/L(2) and ACV-resistant HSV-1/L(2)/R strains in Vero cell culture. Viral population resistant to Hp-ACV (HSV-1/L(2)/R(Hp-ACV)) was developed much slower than ACV-resistant population. The analysis of Hp-ACV-resistant clones isolated from the HSV-1/L(2)/R(Hp-ACV) population demonstrated their partial cross-resistance to ACV. The mutations determining the resistance of HSV-1 clones to Hp-ACV were partly overlapped with mutations defining ACV resistance but did not always coincide. HSV-1/L(2)/R(Hp-ACV) herpes virus thymidine kinase is shortened from the C-terminus by 100 amino acid residues in length.

  1. Analysis of the stress resistance of commercial wine yeast strains.

    PubMed

    Carrasco, P; Querol, A; del Olmo, M

    2001-06-01

    Alcoholic fermentation is an essential step in wine production that is usually conducted by yeasts belonging to the species Saccharomyces cerevisiae. The ability to carry out vinification is largely influenced by the response of yeast cells to the stress conditions that affect them during this process. In this work, we present a systematic analysis of the resistance of 14 commercial S. cerevisiae wine yeast strains to heat shock, ethanol, oxidative, osmotic and glucose starvation stresses. Significant differences were found between these yeast strains under certain severe conditions, Vitilevure Pris Mouse and Lalvin T73 being the most resistant strains, while Fermiblanc arom SM102 and UCLM S235 were the most sensitive ones. Induction of the expression of the HSP12 and HSP104 genes was analyzed. These genes are reported to be involved in the tolerance to several stress conditions in laboratory yeast strains. Our results indicate that each commercial strain shows a unique pattern of gene expression, and no clear correlation between the induction levels of either gene and stress resistance under the conditions tested was found. However, the increase in mRNA levels in both genes under heat shock indicates that the molecular mechanisms involved in the regulation of their expression by stress function in all of the strains.

  2. 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.

  3. Cross-resistance to insecticides in a malathion-resistant strain of Ceratitis capitata (Diptera: Tephritidae).

    PubMed

    Couso-Ferrer, Francisco; Arouri, Rabeh; Beroiz, Beatriz; Perera, Nathalia; Cervera, Amelia; Navarro-Llopis, Vicente; Castañera, Pedro; Hernández-Crespo, Pedro; Ortegoa, Félix

    2011-08-01

    Resistance to malathion has been reported in field populations of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), in areas of Spain where an intensive use of this insecticide was maintained for several years. The main goal of this study was to determine whether resistance to malathion confers cross-resistance to different types of insecticides. Susceptibility bioassays showed that the malathion-resistant W-4Km strain (176-fold more resistant to malathion than the susceptible C strain) has moderate levels of cross-resistance (three- to 16-fold) to other organophosphates (trichlorphon, diazinon, phosmet and methyl-chlorpyrifos), the carbamate carbaryl, the pyrethroid lambda-cyhalothrin, and the benzoylphenylurea derivative lufenuron, whereas cross-resistance to spinosad was below two-fold. The W-4Km strain was selected with lambda-cyhalothrin to establish the lambda-cyhalothrin-resistant W-1Klamda strain (35-fold resistant to lambda-cyhalothrin). The synergistic activity of the esterase inhibitor DEF with lambda-cyhalothrin and the increase in esterase activity in the W-1Klamda strain suggests that esterases may be involved in the development of resistance to this insecticide. Our results showed that resistance to malathion may confer some degree of cross-resistance to insecticides currently approved for the control of Mediterranean fruit fly in citrus crops (lambda-cyhalothrin, lufenuron, and methyl-chlorpyrifos). Especially relevant is the case of lambda-cyhalothrin, because we have shown that resistance to this insecticide can rapidly evolve to levels that may compromise its effectiveness in the field.

  4. Cross-resistance to insecticides in a malathion-resistant strain of Ceratitis capitata (Diptera: Tephritidae).

    PubMed

    Couso-Ferrer, Francisco; Arouri, Rabeh; Beroiz, Beatriz; Perera, Nathalia; Cervera, Amelia; Navarro-Llopis, Vicente; Castañera, Pedro; Hernández-Crespo, Pedro; Ortegoa, Félix

    2011-08-01

    Resistance to malathion has been reported in field populations of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), in areas of Spain where an intensive use of this insecticide was maintained for several years. The main goal of this study was to determine whether resistance to malathion confers cross-resistance to different types of insecticides. Susceptibility bioassays showed that the malathion-resistant W-4Km strain (176-fold more resistant to malathion than the susceptible C strain) has moderate levels of cross-resistance (three- to 16-fold) to other organophosphates (trichlorphon, diazinon, phosmet and methyl-chlorpyrifos), the carbamate carbaryl, the pyrethroid lambda-cyhalothrin, and the benzoylphenylurea derivative lufenuron, whereas cross-resistance to spinosad was below two-fold. The W-4Km strain was selected with lambda-cyhalothrin to establish the lambda-cyhalothrin-resistant W-1Klamda strain (35-fold resistant to lambda-cyhalothrin). The synergistic activity of the esterase inhibitor DEF with lambda-cyhalothrin and the increase in esterase activity in the W-1Klamda strain suggests that esterases may be involved in the development of resistance to this insecticide. Our results showed that resistance to malathion may confer some degree of cross-resistance to insecticides currently approved for the control of Mediterranean fruit fly in citrus crops (lambda-cyhalothrin, lufenuron, and methyl-chlorpyrifos). Especially relevant is the case of lambda-cyhalothrin, because we have shown that resistance to this insecticide can rapidly evolve to levels that may compromise its effectiveness in the field. PMID:21882703

  5. 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

  6. 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.

  7. 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.

  8. Susceptibility of different mice strains to okadaic acid, a diarrhetic shellfish poisoning toxin.

    PubMed

    Suzuki, Hodaka

    2012-08-01

    The mouse bioassay is widely used to detect diarrhetic shellfish poisoning (DSP) toxins. To the best of our knowledge, however, there have been no reports specifically on strain differences in susceptibility to DSP toxins. In this study, we investigated the susceptibility of different mice strains to okadaic acid (OA), one of the representative DSP toxins. A lethal dose of OA was injected intraperitoneally (i.p.) into mice. The mice were observed until 24 h after injection. Five inbred strains (A/J, BALB/c, C3H/He, C57BL/6, and DBA/2) and two non-inbred strains (ddY, and ICR) of mice were compared. All the mice were male, weighed 16-20 g, and were 4-5 weeks old. The lethality was 90-100% in the A/J, BALB/c, ddY, and ICR strains, 70-80% in the C3H/He and C57BL/6 strains, and 40% in DBA/2 strain. Survival analysis showed that the BALB/c, C57BL/6, ddY, and ICR strains died earlier and the A/J, C3H/He and DBA/2 strains survived longer. These results indicate that significant differences may exist in the susceptibility of mice strains to OA.

  9. 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

  10. Evaluation of a fully human monoclonal antibody against multiple influenza A viral strains in mice and a pandemic H1N1 strain in nonhuman primates.

    PubMed

    Song, Aihua; Myojo, Kensuke; Laudenslager, John; Harada, Daisuke; Miura, Toru; Suzuki, Kazuo; Kuni-Kamochi, Reiko; Soloff, Rachel; Ohgami, Kinya; Kanda, Yutaka

    2014-11-01

    Influenza virus is a global health concern due to its unpredictable pandemic potential. Frequent mutations of surface molecules, hemagglutinin (HA) and neuraminidase (NA), contribute to low efficacy of the annual flu vaccine and therapeutic resistance to standard antiviral agents. The populations at high risk of influenza virus infection, such as the elderly and infants, generally mount low immune responses to vaccines, and develop severe disease after infection. Novel therapeutics with high effectiveness and mutation resistance are needed. Previously, we described the generation of a fully human influenza virus matrix protein 2 (M2) specific monoclonal antibody (mAb), Z3G1, which recognized the majority of M2 variants from natural viral isolates, including highly pathogenic avian strains. Passive immunotherapy with Z3G1 significantly protected mice from the infection when administered either prophylactically or 1-2days post infection. In the present study, we showed that Z3G1 significantly protected mice from lethal infection when treatment was initiated 3days post infection. In addition, therapeutic administration of Z3G1 reduced lung viral titers in mice infected with different viral strains, including amantadine and oseltamivir-resistant strains. Furthermore, prophylactic and therapeutic administration of Z3G1 sustained O2 saturation and reduced lung pathology in monkeys infected with a pandemic H1N1 strain. Finally, de-fucosylated Z3G1 with an IgG1/IgG3 chimeric Fc region was generated (AccretaMab® Z3G1), and showed increased ADCC and CDC in vitro. Our data suggest that the anti-M2 mAb Z3G1 has great potential as a novel anti-flu therapeutic agent.

  11. Various Levels of Cross-Resistance to Bacillus sphaericus Strains in Culex pipiens (Diptera: Culicidae) Colonies Resistant to B. sphaericus Strain 2362

    PubMed Central

    Nielsen-LeRoux, Christina; Rao, D. Raghunatha; Murphy, Jittawadee Rodcharoen; Carron, Alexandre; Mani, T. R.; Hamon, Sylviane; Mulla, Mir S.

    2001-01-01

    We studied the cross-resistance to three highly toxic Bacillus sphaericus strains, IAB-59 (serotype H6), IAB-881 (serotype H3), and IAB-872 (serotype H48), of four colonies of the Culex pipiens complex resistant to B. sphaericus 2362 and 1593, both of which are serotype H5a5b strains. Two field-selected highly resistant colonies originating from India (KOCHI, 17,000-fold resistance) and France (SPHAE, 23,000-fold resistance) and a highly resistant laboratory-selected colony from California (GeoR, 36,000-fold resistance) showed strong cross-resistance to strains IAB-881 and IAB-872 but significantly weaker cross-resistance to IAB-59 (3- to 43-fold resistance). In contrast, a laboratory-selected California colony with low-level resistance (JRMM-R, 5-fold resistance) displayed similar levels of resistance (5- to 10-fold) to all of the B. sphaericus strains tested. Thus, among the mosquitocidal strains of B. sphaericus we identified a strain, IAB-59, which was toxic to several Culex colonies that were highly resistant to commercial strains 2362 and 1593. Our analysis also indicated that strain IAB-59 may possess other larvicidal factors. These results could have important implications for the development of resistance management strategies for area-wide mosquito control programs based on the use of B. sphaericus preparations. PMID:11679325

  12. Susceptibility and resistance to Echinococcus granulosus infection: Associations between mouse strains and early peritoneal immune responses.

    PubMed

    Mourglia-Ettlin, Gustavo; Merlino, Alicia; Capurro, Rafael; Dematteis, Sylvia

    2016-03-01

    In helminth infections, there are no easy associations between host susceptibility and immune responses. Interestingly, immunity to cestodes - unlike most helminths - seems to require Th1-type effectors. In this sense, we reported recently that Balb/c and C57Bl/6 mice are high and low susceptible strains, respectively, to experimental infection by Echinococcus granulosus. However, the role of the early cellular peritoneal response in such differential susceptibility is unknown. Here, we analyzed the kinetics of cytokines expression and cellular phenotypes in peritoneal cells from infected Balb/c and C57Bl/6 mice. Additionally, Principal Components Analysis (PCA) were conducted to highlight the most relevant differences between strains. Finally, the anti-parasite activities of peritoneal cells were assessed through in vitro systems. PCAs clustered C57Bl/6 mice by their early mixed IL-5/TNF-α responses and less intense expression of Th2-type cytokines. Moreover, they exhibited lower counts of eosinophils and higher numbers of macrophages and B cells. Functional studies showed that peritoneal cells from infected C57Bl/6 mice displayed greater anti-parasite activities, in accordance with higher rates of NO production and more efficient ADCC responses. In conclusion, mild Th2-responses and active cellular mechanisms are key determinants in murine resistance to E. granulosus infection, supporting the cestode immune exception among helminth parasites. PMID:26658113

  13. Susceptibility and resistance to Echinococcus granulosus infection: Associations between mouse strains and early peritoneal immune responses.

    PubMed

    Mourglia-Ettlin, Gustavo; Merlino, Alicia; Capurro, Rafael; Dematteis, Sylvia

    2016-03-01

    In helminth infections, there are no easy associations between host susceptibility and immune responses. Interestingly, immunity to cestodes - unlike most helminths - seems to require Th1-type effectors. In this sense, we reported recently that Balb/c and C57Bl/6 mice are high and low susceptible strains, respectively, to experimental infection by Echinococcus granulosus. However, the role of the early cellular peritoneal response in such differential susceptibility is unknown. Here, we analyzed the kinetics of cytokines expression and cellular phenotypes in peritoneal cells from infected Balb/c and C57Bl/6 mice. Additionally, Principal Components Analysis (PCA) were conducted to highlight the most relevant differences between strains. Finally, the anti-parasite activities of peritoneal cells were assessed through in vitro systems. PCAs clustered C57Bl/6 mice by their early mixed IL-5/TNF-α responses and less intense expression of Th2-type cytokines. Moreover, they exhibited lower counts of eosinophils and higher numbers of macrophages and B cells. Functional studies showed that peritoneal cells from infected C57Bl/6 mice displayed greater anti-parasite activities, in accordance with higher rates of NO production and more efficient ADCC responses. In conclusion, mild Th2-responses and active cellular mechanisms are key determinants in murine resistance to E. granulosus infection, supporting the cestode immune exception among helminth parasites.

  14. 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

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

    PubMed Central

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

    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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Foster dams rear fighters: strain-specific effects of within-strain fostering on aggressive behavior in male mice.

    PubMed

    Cox, Kimberly H; So, Nina L T; Rissman, Emilie F

    2013-01-01

    It is well known that genes and environment interact to produce behavioral phenotypes. One environmental factor with long-term effects on gene transcription and behavior is maternal care. A classic paradigm for examining maternal care and genetic interactions is to foster pups of one genetic strain to dams of a different strain ("between-strain fostering"). In addition, fostering to a dam of the same strain ("within-strain fostering") is used to reduce indirect effects, via behavioral changes in the dams, of gestation treatments on offspring. Using within-and between-strain fostering we examined the contributions of genetics/prenatal environment, maternal care, and the effects of fostering per se, on adult aggressive behavior in two inbred mouse strains, C57BL/6J (B6) and DBA/2J (DBA). We hypothesized that males reared by dams of the more aggressive DBA strain would attack intruders faster than those reared by B6 dams. Surprisingly, we found that both methods of fostering enhanced aggressive behavior, but only in B6 mice. Since all the B6 offspring are genetically identical, we asked if maternal behavior of B6 dams was affected by the relatedness of their pups. In fact, B6 dams caring for foster B6 pups displayed significantly reduced maternal behaviors. Finally, we measured vasopressin and corticotrophin releasing hormone mRNA in the amygdalae of adult B6 males reared by foster or biological dams. Both genes correlated with aggressive behavior in within-strain fostered B6 mice, but not in mice reared by their biological dams. In sum, we have demonstrated in inbred laboratory mice, that dams behave differently when rearing their own newborn pups versus pups from another dam of the same strain. These differences in maternal care affect aggression in the male offspring and transcription of Avp and Crh in the brain. It is likely that rearing by foster dams has additional effects and implications for other species.

  2. Bacteriophage in the treatment of experimental septicemic mice from a clinical isolate of multidrug resistant Klebsiella pneumoniae.

    PubMed

    Vinodkumar, C S; Neelagund, Y F; Kalsurmath, Suneeta

    2005-03-01

    Drug resistance is the major cause of increase in morbidity and mortality in neonates. The emergence of antibiotic-resistant bacterial strains requires the exploration of alternative antibacterial therapies and the concern that human kind in re-entering the 'pre-antibiotic era' has become very real and the development of alternative anti-infection modalities has become one of the highest priorities of modern medicine and biotechnology. This has spurred biomedical researchers to expand their efforts to identify new technologies and products that employ novel mechanism of action against the "super-bugs". One of such alternatives stems up from an old idea is the bacteriophage therapy, which led our group to study the ability of bacterial viruses (bacteriophages or phages) to rescue septicemic mice with multidrug resistant (MDR) Klebsiella pneumoniae isolated from neonatal septicemia. The phage strain used in this study had lytic activity against a wide range of clinical isolates of MDR Klebsiella pneumoniae. One of these MDR Klebsiella strain was used to induce septicemia in mice by intraperitoneal (i.p.) injection of 10(9) CFU. The resulting bacteremia was fatal within 48 h. A single i.p. injection of 3x10(8) PFU of the phage strain administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue septicemic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of septicemic mice could be affected only by phage strains able to grow in vitro on the bacterial host used to infect the animals and when such strains are heat inactivated they lose their ability to rescue the infected mice.

  3. Characterization of the inflammatory response in the central nervous system of mice susceptible or resistant to demyelination by Theiler's virus.

    PubMed

    Lindsley, M D; Rodriguez, M

    1989-04-15

    Intracerebral inoculation of mice with Theiler's murine encephalomyelitis virus results in an intense inflammatory response of mononuclear leukocytes which infiltrate into the central nervous system. Resistant strains of mice have the ability to clear virus whereas susceptible strains become infected persistently and are associated with chronic demyelination which is proposed to be immune-mediated. In an attempt to better understand the role of the immune response during demyelination, mononuclear leukocytes were isolated from the central nervous system of infected mice and stained by an immunoperoxidase technique with anti-Thy-1.2, anti-L3T4, anti-Lyt-2 and anti-MAC-1 mAb. Infection of susceptible SJL/J mice resulted in a biphasic immune response which peaked on days 7 and 27 post-infection. In contrast, a single peak (day 7) was observed in resistant C57BL/10SNJ mice. The presence of Thy-1.2, L3T4, and MAC-1+ cells was similar between the two strains. However, although the number of Lyt-2+ cells peaked on day 7 in C57BL/10SNJ mice, they were not detected in SJL/J mice until 14 days post-infection and gradually increased in number over the course of infection. To further study the role of T cells in demyelination, serial frozen sections of brain and spinal cord were stained for the presence of Lyt-2 and L3T4+ cells in the lesions of chronically infected SJL/J mice. L3T4+ cells were observed predominantly in perivascular regions while Lyt-2+ cells were observed infiltrating the parenchyma. These results provide further evidence that Lyt-2+ lymphocytes are important in the mechanism of susceptibility/resistance to Theiler's murine encephalomyelitis virus-induced demyelination.

  4. Modification of resistance of mice to Naegleria fowleri infections.

    PubMed Central

    Adams, A C; John, D T; Bradley, S G

    1976-01-01

    Naegleria fowleri, which produces a fatal meningoencephalitis in humans, is also able to produce a progressive and fatal disease in mice. The course of the disease in DUB/ICR mice is dependent upon the infecting dose of organisms, whether administered intraperitoneally (i.p.) or intravenously (i.v.). All of the mice receiving 10(7) trophozoites/mouse i.v. or 4.85 X 10(7) trophozoites/mouse i.p. were killed within 10 days. Escherichia coli O26:B6 lipopolysaccharide, administered at a dose of 1 mg/kg 24 h prior to N. fowleri, afforded some protection for several days after challenge, but by day 8 there was no difference in survival of untreated and endotoxin-treated mice. No significant protection was afforded by a complex of lipid A with concanavalin A (ConA) or bovine serum albumin (BSA) or by dimethylmyristamide-BSA, dimethylmyristamide, BSA, beta-hydroxymyristic acid-ConA, beta-hydroxymyristic acid, ConA, myristic acid-BSA, or myristic acid. Mice surviving primary i.v. or i.p. challenge doses of N. fowleri, 5 X 10(6) and 10(7) trophozoites/mouse, respectively, were highly resistant to rechallenge with an i.v. dose of organisms (5 X 10(6) Naegleria/mouse) that produced uniformly fatal disease in untreated control mice. PMID:1270145

  5. In vivo efficacy of a new fluoroquinolone, sparfloxacin, against penicillin-susceptible and -resistant and multiresistant strains of Streptococcus pneumoniae in a mouse model of pneumonia.

    PubMed Central

    Azoulay-Dupuis, E; Vallee, E; Veber, B; Bedos, J P; Bauchet, J; Pocidalo, J J

    1992-01-01

    The increasing emergence of penicillin-resistant and multiresistant strains of Streptococcus pneumoniae may pose a problem in coming years. We therefore compared sparfloxacin, a new fluoroquinolone with improved potency against streptococci, with amoxicillin, the "gold standard" in this setting, and another fluoroquinolone, ciprofloxacin, in a mouse pneumonia model. Their efficacies against penicillin-susceptible (serotype 3), macrolide-resistant (serotype 1), penicillin-resistant (serotype 23), and multiresistant (serotype 6) S. pneumoniae strains were evaluated. Immunocompetent Swiss mice (serotypes 1 and 3) and leukopenic mice (serotypes 6 and 23) were infected by peroral tracheal delivery of 10(4) to 10(6) CFU. Subcutaneous injections of antibiotics were initiated at 6, 18, 48, or 72 h after infection (six injections at 12-h intervals). In the immunocompetent mice, 100% survival was obtained with sparfloxacin (50 mg/kg) and amoxicillin (5 mg/kg) against both penicillin-susceptible and macrolide-resistant strains; ciprofloxacin gave significantly lower survival rates. Two to four injections of sparfloxacin completely cleared bacteria from lungs and blood; the most rapid eradication was achieved with amoxicillin. Sparfloxacin also fully protected leukopenic mice against penicillin-resistant strains. The dose of amoxicillin (50 mg/kg) required to protect mice and eradicate penicillin-resistant and multiresistant strains was 10 times higher than that effective against penicillin-susceptible strains. The microbiological and pharmacokinetic properties of sparfloxacin (e.g., the time during which concentrations exceed the MIC of the test pathogen) accounted for its efficacy against susceptible and resistant strains of S. pneumoniae in this model. PMID:1336343

  6. Reduced cerebral infection of Neospora caninum in BALB/c mice vaccinated with recombinant Brucella abortus RB51 strains expressing N. caninum SRS2 and GRA7 proteins.

    PubMed

    Vemulapalli, Ramesh; Sanakkayala, Neelima; Gulani, Jatinder; Schurig, Gerhardt G; Boyle, Stephen M; Lindsay, David S; Sriranganathan, Nammalwar

    2007-09-30

    Neospora caninum, an obligate intracellular protozoan parasite, is the causative agent of bovine neosporosis, an important disease affecting the reproductive performance of cattle worldwide. Currently there is no effective vaccine available to prevent N. caninum infection in cattle. In this study, we examined the feasibility of developing a live, recombinant N. caninum vaccine using Brucella abortus vaccine strain RB51 as the expression and delivery vector. We generated two recombinant RB51 strains each expressing SRS2 (RB51/SRS2) or GRA7 (RB51/GRA7) antigens of N. caninum. BALB/c mice immunized by single intraperitoneal inoculation of the recombinant RB51 strains developed IgG antibodies specific to the respective N. caninum antigen. In vitro stimulation of splenocytes from the vaccinated mice with specific antigen resulted in the production of interferon-gamma, but not IL-5 or IL-10, suggesting the development of a Th1 type immune response. Upon challenge with N. caninum tachyzoites, mice vaccinated with strain RB51/SRS2, but not RB51/GRA7, showed significant resistance to cerebral infection when compared to the RB51 vaccinated mice, as determined by the tissue parasite load using a real-time quantitative TaqMan assay. Interestingly, mice vaccinated with either strain RB51 or RB51/GRA7 also contained significantly lower parasite burden in their brains compared to those inoculated with saline. Mice vaccinated with strain RB51/SRS2 or RB51/GRA7 were protected to the same extent as the strain RB51 vaccinated mice against challenge with B. abortus virulent strain 2308. These results suggest that a recombinant RB51 strain expressing an appropriate protective antigen(s), such as SRS2 of N. caninum, can confer protection against both neosporosis and brucellosis.

  7. Minute virus of mice: antibody response, viral shedding, and persistence of viral DNA in multiple strains of mice.

    PubMed

    Janus, Lydia M; Mähler, Michael; Köhl, Wiebke; Smoczek, Anna; Hedrich, Hans J; Bleich, Andre

    2008-08-01

    Minute virus of mice (MVM) is a major concern for laboratory animal facilities because it remains with considerably high prevalence despite strict barrier systems. The aim of this study was to elucidate potential risks associated with MVM infection by investigating the role of the genetic background on antibody production and persistence as well as viral shedding. Mice of various strains and stocks were inoculated oronasally with the immunosuppressive strain MVMi; in addition, natural infection was modeled through contact exposure. As determined by serology, seroconversion and serum levels of IgG differed considerably among strains and stocks, especially in the contact-exposed group. For example, C57BL/6J mice responded well to exposure in contrast to FVB/N, NMRI, ICR, and C3H/HeN mice. Titration studies indicated that the viral dose necessary to induce seroconversion was strain-dependent. Experiments to dissect the role of the major histocompatibility complex haplotype in the response to MVMi gave inconclusive results. To detect viral persistence, spleens and feces were analyzed by PCR at 16 wk after exposure, and the infectivity of PCR-positive spleens was investigated by IP and oronasal inoculation of naive mice. Although DNA was detected in the spleens of some mice, feces remained negative, and naive mice were not infected by inoculation. In addition, viral shedding declined rapidly after day 20 postinoculation. In summary, the data show that seroconversion and antibody response to MVMi infection depend on the genetic background of mice, with the infective dose being a critical factor. The role of viral DNA in chronically infected mice will require further elucidation.

  8. New insights in leptin resistance mechanisms in mice.

    PubMed

    Balland, Eglantine; Cowley, Michael A

    2015-10-01

    Leptin resistance is one of the main challenges of obesity. To date, two levels of resistance have been identified, first a decreased rate of leptin uptake into the brain and secondly a diminished central response to leptin. New findings have identified the mechanisms of leptin transport and demonstrated that it can be rescued in obesity, but it did not overcome the problem of central resistance. Alteration in the actions of leptin following diet-induced obesity (DIO) appears to be a multifactorial condition. Several phosphatases are inhibiting leptin signaling pathways in a pathological way. Besides, hypothalamic inflammation alters the neuronal circuits that control metabolism. Recent studies describing both mechanisms (inhibition of leptin signaling and inflammation), have provided key insights to potential new targets for treatment. However, recent data showing that DIO mice may conserve a cellular and physiological response to endogenous leptin, highlights the need to redefine the concept of "leptin resistance".

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

    PubMed

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

    2015-05-11

    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.

  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. Dissemination of antibiotic resistance in methicillin-resistant Staphylococcus aureus and vancomycin-resistant S aureus strains isolated from hospital effluents.

    PubMed

    Mandal, Santi M; Ghosh, Ananta K; Pati, Bikas R

    2015-12-01

    Vancomycin-resistant Staphylococcus aureus (VRSA) and methicillin-resistant S aureus (MRSA) strains were examined in hospital effluents. Most S aureus strains are resistant to methicillin (MRSA), followed by tetracycline. Approximately 15% of MRSA strains are also resistant to vancomycin (VRSA). All VRSA strains developed a VanR/VanS-regulated 2-component system of VanA-type resistance in their genome. Results indicate that there is a possibility of developing resistance to aminoglycosides by VRSA strains in the near future.

  12. 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.

  13. Immune resistance of semisyngeneic F1 hybrid mice to lymphoma grafts differs from natural hybrid resistance in its genetic pattern

    SciTech Connect

    Klein, G.O.; Klein, G.

    1984-07-01

    Resistance of semisyngeneic F1 hybrid mice immunized three times with irradiated tumor cells was compared to the genetic pattern of natural hybrid resistance to challenge with live tumor cells. Syngeneic mice responded equally well to immunization with all five hemopoietic tumor lines tested as the naturally much more highly resistant F1 hybrids. Natural hybrid resistance was found to be severely reduced by sublethal irradiation with 4 Gy, in contrast to hybrid resistance to parental bone marrow.

  14. Origins of Community Strains of Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Charlebois, Edwin D.; Perdreau-Remington, Françoise; Kreiswirth, Barry; Bangsberg, David R.; Ciccarone, Daniel; Diep, Binh A.; Ng, Valerie L.; Chansky, Kimberly; Edlin, Brian; Chambers, Henry F.

    2008-01-01

    To characterize methicillin-resistant Staphylococcus aureus (MRSA) strains circulating in the community, we identified predictors of isolating community MRSA and genotyped a sample of MRSA collected from a community-based, high-risk population. Computerized databases of the Community Health Network of San Francisco and the Clinical Microbiology Laboratory were searched electronically for the years 1992–1999 to identify community-onset infections caused by MRSA. Sequential analyses were performed to identify predictors of MRSA strains. The majority (58%) of infections were caused by strains traceable to the hospital or to long-term care facilities. Injection drug use was associated with infections that were not associated with health care settings. Genotypes for 20 of 35 MRSA isolates recovered from injection drug users did not match any of >600 genotypes of clinical isolates. In a nonoutbreak setting, the hospital was the main source of community MRSA; however, the presence of genetically distinct and diverse MRSA strains indicates MRSA strains now also originate from the community. PMID:15206052

  15. 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

  16. Clarithromycin Resistance Mechanisms of Epidemic β-Lactamase-Nonproducing Ampicillin-Resistant Haemophilus influenzae Strains in Japan.

    PubMed

    Seyama, Shoji; Wajima, Takeaki; Nakaminami, Hidemasa; Noguchi, Norihisa

    2016-05-01

    The aim of this study was to clarify the clarithromycin resistance mechanisms of β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae strains. In all clarithromycin-resistant strains, the transcript level of acrB was significantly elevated, and these strains had a frameshift mutation in acrR Introduction of the acrR mutation into H. influenzae Rd generated a clarithromycin-resistant transformant with the same MIC as the donor strain. Our results indicate that the acrR mutation confers clarithromycin resistance by the increasing the transcription of acrB.

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

    PubMed Central

    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

  18. 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

  19. 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

    2016-09-14

    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.

  20. Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

    PubMed Central

    Jung, Yang-Hee; Hong, Sa-Ik; Ma, Shi-Xun; Hwang, Ji-Young; Kim, Jun-Sup; Lee, Ju-Hyun; Seo, Jee-Yeon; Lee, Seok-Yong; Jang, Choon-Gon

    2014-01-01

    Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in sucrose intake test (SIT) and open field test (OFT). However, the two strains showed quite different responses in forced swimming test (FST) and novelty-suppressed feeding (NSF) test after 3 weeks of CMS treatment. Only C57BL/6 mice displayed the depression- and anxiety-like behavioral effects in response to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression- and anxiety-like behaviors using CMS in ICR and C57BL/6 mice. PMID:25414777

  1. Strain-specific regulation of striatal phenotype in Drd2-eGFP BAC transgenic mice.

    PubMed

    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

    2012-07-01

    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 mice--mice possessing a BAC transgene with a D(2) 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 (SW) 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 that are hemizygous for the Drd2 BAC transgene provides a reliable tool for studying basal ganglia function.

  2. 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

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

    PubMed

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

    1996-11-01

    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.

  4. 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

  5. Effect of a combination of the new antischistosomal drug Ro 15-5458 and praziquantel on different strains of Schistosoma mansoni infected mice.

    PubMed

    Kamel, G; Metwally, A; Guirguis, F; Nessim, N G; Noseir, M

    2000-04-01

    The possible additive or synergistic effects of both praziquantel (CAS 55268-74-1) and a new antischistosomal drug, Ro 15-5458 (10-(2-diethylamino)thyl)-9-acridanone(thiazolidin-2-yl-i dene)hydrazone, CAS 92928-47-7) were studied in two different strains of Schistosoma mansoni infected mice, namely CD susceptible and SO4 resistant strains. Assessment of cure was performed using the following parameters: hepatic and intestinal tissue egg load and distribution, oogram changes in the small intestine and histopathological examination of the mice livers. In this study, a combination was used between 1/3 the curative doses of praziquantel and Ro 15-5458. This combination therapy proved to be beneficial as regards the percentage parasite reduction and hepatic worm shift (99.4% and 100%, respectively, in the CD susceptible mouse strains, compared to 84.1% and 34.8% in the SO4 resistant strains). Treatment with subcurative doses of praziquantel and Ro 15-5458 resulted in 78.6% intestinal dead ova and 21.4% mature ones. This score shifted to 98.6% and 1.4% dead and mature ova, respectively, in the SO4 resistant strains. Again the range of liver granulomata in the CD susceptible and SO4 resistant strains receiving subcurative doses of both drugs was 4-6 and 2-5, respectively, in five successive low power fields, while in the infected untreated control mice, this range reached 8-11 and 5-9, respectively. Histopathological sections of the liver revealed a small fibrocellular granuloma with few inflammatory cells and excess fibrous collagen tissue deposition in animals undergoing the combination therapy. This contrasts with the large fibrocellular granulomata seen in the infected untreated control mice. These results may be of value in endemic areas of schistosomiasis, due to the unexpected emergence of drug resistance against the currently used antischistosomal drug, praziquantel in these areas. PMID:10800639

  6. 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

  7. Resistance of Rhizobium strains to phygon, spergon, and thiram.

    PubMed

    Odeyemi, O; Alexander, M

    1977-04-01

    Strains of Rhizobium meliloti, Rhizobium sp. nodulating cowpeas, and R. phaseoli derived from cultures susceptible to tetramethylthiuram disulfide (thiram), 2,3-dichloro-1,4-naphthoquinone (phygon), and 2,3,5,6-tetrachloro-p-benzoquinone (spergon), respectively, grew in the presence of high concentrations of the fungicides and converted them to products not toxic to the sensitive rhizobia. The results of chemical assays demonstrated that the pesticides were destroyed by the resistant bacteria but not by the susceptible parent rhizobia. Resting cells of thiram-metabolizing R. meliloti formed large quantities of dimethyldithiocarbamate, dimethylamine, and CS2 from the pesticide. The products were characterized by gas and thin-layer chromatography, colorimetric reactions, and ultraviolet spectrometry. Dimethylamine and CS2 were formed spontaneously from dimethyldithiocarbamate, but the yield was higher in the presence of R. meliloti. The phygon-resistant bacterium converted the fungicide to five metabolites and thereby rendered the chemical nontoxic to a test fungus. The resistant strain of R. phaseoli generated at least one organic product and released about one-third of the chlorine during its detoxication of spergon.

  8. Resistance of Rhizobium strains to phygon, spergon, and thiram.

    PubMed Central

    Odeyemi, O; Alexander, M

    1977-01-01

    Strains of Rhizobium meliloti, Rhizobium sp. nodulating cowpeas, and R. phaseoli derived from cultures susceptible to tetramethylthiuram disulfide (thiram), 2,3-dichloro-1,4-naphthoquinone (phygon), and 2,3,5,6-tetrachloro-p-benzoquinone (spergon), respectively, grew in the presence of high concentrations of the fungicides and converted them to products not toxic to the sensitive rhizobia. The results of chemical assays demonstrated that the pesticides were destroyed by the resistant bacteria but not by the susceptible parent rhizobia. Resting cells of thiram-metabolizing R. meliloti formed large quantities of dimethyldithiocarbamate, dimethylamine, and CS2 from the pesticide. The products were characterized by gas and thin-layer chromatography, colorimetric reactions, and ultraviolet spectrometry. Dimethylamine and CS2 were formed spontaneously from dimethyldithiocarbamate, but the yield was higher in the presence of R. meliloti. The phygon-resistant bacterium converted the fungicide to five metabolites and thereby rendered the chemical nontoxic to a test fungus. The resistant strain of R. phaseoli generated at least one organic product and released about one-third of the chlorine during its detoxication of spergon. PMID:869529

  9. Day/night food consumption in mice is strain and age-dependent.

    PubMed

    Kowal, Małgorzata; Buda-Lewandowska, Dorota; Płytycz, Barbara; Styrna, Józefa

    2002-01-01

    Food consumption was measured during the day (lights on) and the night (lights off) and compared between one outbred and 9 inbred strains of mice (CBA/Kw, C3H, DBA2, KP, BALB/c, C57BL, B10.Amst, B10.BR, B10.BR Y-del) in age groups 30-60, 60-90, 90-120, and more than 120 days. Outbred mice and animals from B10 sublines ate significantly more during nocturnal darkness. Day and night food consumption was similar in KP animals. In mice from the remaining strains there was an apparent age-related shift from nocturnal towards diurnal eating habits.

  10. The Nlrp3 inflammasome, IL-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of Leishmania major in C57BL/6 mice.

    PubMed

    Charmoy, Melanie; Hurrell, Benjamin P; Romano, Audrey; Lee, Sang Hun; Ribeiro-Gomes, Flavia; Riteau, Nicolas; Mayer-Barber, Katrin; Tacchini-Cottier, Fabienne; Sacks, David L

    2016-04-01

    Infection of C57BL/6 mice with most Leishmania major strains results in a healing lesion and clearance of parasites from the skin. Infection of C57BL/6 mice with the L. major Seidman strain (LmSd), isolated from a patient with chronic lesions, despite eliciting a strong Th1 response, results in a nonhealing lesion, poor parasite clearance, and complete destruction of the ear dermis. We show here that in comparison to a healing strain, LmSd elicited early upregulation of IL-1β mRNA and IL-1β-producing dermal cells and prominent neutrophil recruitment to the infected skin. Mice deficient in Nlrp3, apoptosis-associated speck-like protein containing a caspase recruitment domain, or caspase-1/11, or lacking IL-1β or IL-1 receptor signaling, developed healing lesions and cleared LmSd from the infection site. Mice resistant to LmSd had a stronger antigen-specific Th1 response. The possibility that IL-1β might act through neutrophil recruitment to locally suppress immunity was supported by the healing observed in neutropenic Genista mice. Secretion of mature IL-1β by LmSd-infected macrophages in vitro was dependent on activation of the Nlrp3 inflammasome and caspase-1. These data reveal that Nlrp3 inflammasome-dependent IL-1β, associated with localized neutrophil recruitment, plays a crucial role in the development of a nonhealing form of cutaneous leishmaniasis in conventionally resistant mice.

  11. Strain background influences neurotoxicity and behavioral abnormalities in mice expressing the tetracycline transactivator.

    PubMed

    Han, Harry J; Allen, Carolyn C; Buchovecky, Christie M; Yetman, Michael J; Born, Heather A; Marin, Miguel A; Rodgers, Shaefali P; Song, Bryan J; Lu, Hui-Chen; Justice, Monica J; Probst, Frank J; Jankowsky, Joanna L

    2012-08-01

    The tet-off system has been widely used to create transgenic models of neurological disorders including Alzheimer's, Parkinson's, Huntington's, and prion disease. The utility of this system lies in the assumption that the tetracycline transactivator (TTA) acts as an inert control element and does not contribute to phenotypes under study. Here we report that neuronal expression of TTA can affect hippocampal cytoarchitecture and behavior in a strain-dependent manner. While studying neurodegeneration in two tet-off Alzheimer's disease models, we unexpectedly discovered neuronal loss within the dentate gyrus of single transgenic TTA controls. Granule neurons appeared most sensitive to TTA exposure during postnatal development, and doxycycline treatment during this period was neuroprotective. TTA-induced degeneration could be rescued by moving the transgene onto a congenic C57BL/6J background and recurred on reintroduction of either CBA or C3H/He backgrounds. Quantitative trait analysis of B6C3 F2 TTA mice identified a region on Chromosome 14 that contains a major modifier of the neurodegenerative phenotype. Although B6 mice were resistant to degeneration, they were not ideal for cognitive testing. F1 offspring of TTA C57BL/6J and 129X1/SvJ, FVB/NJ, or DBA/1J showed improved spatial learning, but TTA expression caused subtle differences in contextual fear conditioning on two of these backgrounds, indicating that strain and genotype can interact independently under different behavioral settings. All model systems have limitations that should be recognized and mitigated where possible; our findings stress the importance of mapping the effects caused by TTA alone when working with tet-off models.

  12. 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

  13. Clonality of multidrug-resistant nontypeable strains of Haemophilus influenzae.

    PubMed Central

    Fusté, M C; Pineda, M A; Palomar, J; Viñas, M; Lorén, J G

    1996-01-01

    The genetic structure of a population of multidrug-resistant nontypeable (unencapsulated) Haemophilus influenzae strains isolated at a hospital in Barcelona, Spain, was investigated by using multilocus enzyme electrophoresis to determine the allelic variation in 15 structural loci. In our study we have also included some antimicrobial agent-susceptible strains isolated at the same hospital. All enzymes were polymorphic for two to eight electromorphs, and the analysis revealed 43 distinct electrophoretic types among the 44 isolates. The mean genetic diversity of the entire population was 0.55. Multilocus linkage disequilibrium analysis of the isolates revealed a strong association between alleles, suggesting little possibility of recombination. Furthermore, the dendrogram and the allele mismatch distribution are typical of a population with no extensive genetic mixing. PMID:8897179

  14. Impact of Antimicrobial Usage on Antimicrobial Resistance in Commensal Escherichia coli Strains Colonizing Broiler Chickens▿

    PubMed Central

    Smith, J. L.; Drum, D. J. V.; Dai, Y.; Kim, J. M.; Sanchez, S.; Maurer, J. J.; Hofacre, C. L.; Lee, M. D.

    2007-01-01

    Escherichia coli strains isolated from commercial broilers and an experimental flock of chickens were screened to determine phenotypic expression of antimicrobial resistance and carriage of drug resistance determinants. The goal of this study was to investigate the influence of oxytetracycline, sarafloxacin, and enrofloxacin administration on the distribution of resistance determinants and strain types among intestinal commensal E. coli strains isolated from broiler chickens. We detected a high prevalence of resistance to drugs such as tetracycline (36 to 97%), sulfonamides (50 to 100%), and streptomycin (53 to 100%) in E. coli isolates from treated and untreated flocks. These isolates also had a high prevalence of class 1 integron carriage, and most of them possessed the streptomycin resistance cassette, aadA1. In order to investigate the contribution of E. coli strain distribution to the prevalence of antimicrobial resistance and the resistance determinants, isolates from each flock were DNA fingerprinted by enterobacterial repetitive intergenic consensus sequence (ERIC) PCR. Although very diverse E. coli strain types were detected, four ERIC strain types were present on all of the commercial broiler farms, and two of the strains were also found in the experimental flocks. Each E. coli strain consisted of both susceptible and antimicrobial agent-resistant isolates. In some instances, isolates of the same E. coli strain expressed the same drug resistance patterns although they harbored different tet determinants or streptomycin resistance genes. Therefore, drug resistance patterns could not be explained solely by strain prevalence, indicating that mobile elements contributed significantly to the prevalence of resistance. PMID:17194843

  15. Methicillin-Resistant Staphylococcus aureus in Northeastern Scotland in 2003 to 2007: Evolving Strain Distribution and Resistance Patterns▿

    PubMed Central

    Hunt, A. C.; Edwards, B.; Girvan, E. K.; Cosgrove, B.; Edwards, G. F. S.; Gould, I. M.

    2011-01-01

    This study explored strain distribution and resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) over a 5-year period in northeastern Scotland. We noted a shift in the relative rates of epidemic strains and an increase in community-associated strains. Use of oral antibiotics to eradicate throat carriage may have contributed to trimethoprim resistance, which was observed to increase 10-fold. PMID:21411588

  16. Establishment and characterization of the MSKR inbred strain originated from Japanese wild mice (Mus musculus molossinus).

    PubMed

    Wada, A; Kakizoe-Ishida, Y; Katoh, H; Muguruma, K; Ebukuro, M; Okumoto, M; Tsudzuki, M

    2000-04-01

    A new inbred strain, MSKR, originated from Japanese wild mice was established in April, 1998. The MSKR mice were 60% of the C57BL/6N inbred mice in the 60-day body weight. Tail length/head-body length and hind-foot length/head-body length of the MSKR mice were significantly smaller than those of the C57BL/6N mice (0.896 vs 1.061, 0.189 vs 0.204), but ear length/head-body length of the MSKR mice was significantly larger than that of the C57BL/6N mice (0.143 vs 0.137). The age of the first parturition and size of the first litter were 63.20 +/- 2.71 days and 6.20 +/- 0.37, respectively, at the 20th and 22nd inbreeding generations. Genetic characterization of the MSKR strain was performed using 34 microsatellite markers, 29 biochemical markers, 9 immunogenetic markers, 3 coat color markers, and mitochondrial DNA RFLP-haplotypes. The result indicated that this newly established inbred strain has some different gene constitution from already known molossinus and common laboratory strains.

  17. Immunobiotic Lactobacillus rhamnosus improves resistance of infant mice against respiratory syncytial virus infection.

    PubMed

    Chiba, Eriko; Tomosada, Yohsuke; Vizoso-Pinto, Maria Guadalupe; Salva, Susana; Takahashi, Takuya; Tsukida, Kohichiro; Kitazawa, Haruki; Alvarez, Susana; Villena, Julio

    2013-10-01

    Previously we showed that orally administered Lactobacillus rhamnosus CRL1505 beneficially regulated the balance between pro- and anti-inflammatory mediators in the lungs of poly(I:C)-challenged mice, allowing an effective inflammatory response against the TLR3/RIG-I agonist but at the same time reducing tissue damage. The aim of the present study was to investigate whether oral administration of the CRL1505 strain was able to improve resistance against respiratory syncytial virus (RSV) infection in infant mice and to evaluate the immunological mechanisms involved in the immunobiotic effect. We demonstrated that treatment of 3-week old BALB/c mice with L. rhamnosus CRL1505 significantly reduce lung viral loads and tissue injuries after the challenge with RSV. Moreover, we showed that the protective effect achieved by the CRL1505 strain is related to its capacity to differentially modulate respiratory antiviral immune response. Our results shows that IFN-γ and IL-10 secreted in response to L. rhamnosus CRL1505 oral stimulation would modulate the pulmonary innate immune microenvironment conducting to the activation of CD103(+) and CD11b(high) dendritic cells and the generation of CD3(+)CD4(+)IFN-γ(+) Th1 cells with the consequent attenuation of the strong and damaging Th2 reactions associated with RSV challenge. Our results indicate that modulation of the common mucosal immune system by immunobiotics could favor protective immunity against respiratory viral pathogens with a high attack rate in early infancy, such as RSV.

  18. Pregnancy reduces the genetic resistance of C57BL/6 mice to Listeria monocytogenes infection by intragastric inoculation

    PubMed Central

    Poulsen, Keith P.; Faith, Nancy G.; Steinberg, Howard; Czuprynski, Charles J.

    2011-01-01

    In this study, we compared genetically resistant C57BL/6 and susceptible A/J mice for their resistance to L. monocytogenes infection model during pregnancy. Intragastric infection with modest numbers of bacterial cells (105 CFU) caused reproducible fetal infection and abortion in both mouse strains. Bioluminescence imaging demonstrated dissemination of L. monocytogenes cells from maternal to fetal organs within 3 days of intragastric infection. Although non-pregnant C57BL/6 mice were significantly more resistant to infection than non-pregnant A/J mice, C57BL/6 and A/J mice had similar microbial loads (CFU) in maternal and fetal tissues during pregnancy. Inflammation and necrosis, however, were more severe in A/J mice as evaluated by semi-quantitative histopathology. Although the microbial load in fetal tissues was similar for all fetuses within a single uterus, inflammation and necrosis varied among individual fetuses and placentas. We also noted that the uterus is a target for L. monocytogenes infection in non-pregnant mice. PMID:21320586

  19. Antidepressant-like effects in various mice strains in the tail suspension test.

    PubMed

    Ripoll, Nadège; David, Denis Joseph Paul; Dailly, Eric; Hascoët, Martine; Bourin, Michel

    2003-08-14

    Several studies have reported rodent strain differences in the response to antidepressants in animal models of depression. The aim of the present study was to investigate the potential contribution of genetic factors to antidepressant response in an animal model of depression: the tail suspension test (TST). For this study four mice strains (Swiss and NMRI, two outbred strains and DBA/2 and C57BL/6J Rj, two inbred strains) were submitted to the TST after acute administration of five antidepressants: the tricyclic antidepressants (TCAs) imipramine and desipramine, the selective serotonin (5-HT) reuptake inhibitors (SSRIs) paroxetine and citalopram and the dopamine reuptake inhibitor bupropion. The C57BL/6J Rj strain had a longer baseline immobility time in comparison to the other strains. All antidepressants studied in this work decreased immobility time in the Swiss and C57BL/6J Rj strains. However, the Swiss strain displayed greater sensitivity to citalopram (from 2mg/kg) and C57BL/6J Rj to paroxetine (from 0.5mg/kg). This latter presented a greater size-effect with citalopram than with other strains and reached more than 60% from 8mg/kg. Moreover the size-effect of desipramine, paroxetine and bupropion in Swiss mice was greater than in the other strains in the TST. The NMRI and DBA/2 mice only responded to 5-HT reuptake inhibitors, both selective (paroxetine, citalopram) or non-selective (imipramine). The NMRI strain was more sensitive to imipramine and presented a size-effect (43% at 8mg/kg) superior to those of other strains. DBA/2 strain was more sensitive to citalopram than paroxetine and imipramine. Our results suggest that response to an antidepressant treatment is under control of genetic factors and that the strain of mouse is an important parameter to consider.

  20. 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

  1. Synergy characterization for Enterococcus faecalis strains displaying moderately high-level gentamicin and streptomycin resistance.

    PubMed Central

    Bantar, C E; Micucci, M; Fernandez Canigia, L; Smayevsky, J; Bianchini, H M

    1993-01-01

    Synergy of 14 Enterococcus faecalis strains displaying moderately high-level aminoglycoside resistance (MICs, 500 and 256 to 1,000 micrograms/ml for gentamicin and streptomycin, respectively) was characterized by time-kill studies. All strains proved resistant to penicillin plus the respective aminoglycoside. Strains with moderately high-level aminoglycoside resistance should be considered to exhibit high-level resistance in severe infections. PMID:8349776

  2. Synergy characterization for Enterococcus faecalis strains displaying moderately high-level gentamicin and streptomycin resistance.

    PubMed

    Bantar, C E; Micucci, M; Fernandez Canigia, L; Smayevsky, J; Bianchini, H M

    1993-07-01

    Synergy of 14 Enterococcus faecalis strains displaying moderately high-level aminoglycoside resistance (MICs, 500 and 256 to 1,000 micrograms/ml for gentamicin and streptomycin, respectively) was characterized by time-kill studies. All strains proved resistant to penicillin plus the respective aminoglycoside. Strains with moderately high-level aminoglycoside resistance should be considered to exhibit high-level resistance in severe infections.

  3. Interferon-γ is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice

    PubMed Central

    Murphy, Erin A; Sathiyaseelan, Janaki; Parent, Michelle A; Zou, Baixiang; Baldwin, Cynthia L

    2001-01-01

    Brucella abortus is an intracellular bacterial pathogen that causes chronic infections in humans and a number of agriculturally important species of animals. It has been shown that BALB/c mice are more susceptible to infections with virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In experiments described here, gene knock-out mice were utilized to elucidate some of the salient components of resistance. Resistant C57BL/6 mice with gene deletions or disruptions in the interferon-γ (IFN-γ), perforin or β2-microglobulin genes had decreased abilities to control intracellular infections with B. abortus strain 2308 during the first week after infection. However, only the IFN-γ knock-out mice had a sustained inability to control infections and this resulted in death of the mice at approximately 6 weeks post-infection. These mice had a continual increase in the number of bacterial colony-forming units (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN-γ gene were infected they had more splenic CFU at one week post-infection than control mice but the increase was not statistically significant and by 3 weeks they did not have more CFU than control mice. Moreover, the number of splenic bacteria did not increase in the BALB/c IFN-γ knock-out mice between 6 and 10·5 weeks, although they died at 10·5 weeks, the time by which normal BALB/c mice were clearing the infection. Death in both strains of IFN-γ gene disrupted mice coincided with symptoms of cachexia and macrophages comprised ≥75% of the splenic leucocytes. PMID:11529943

  4. Complete genome sequencing and comparative analysis of the linezolid-resistant Enterococcus faecalis strain DENG1.

    PubMed

    Yu, Zhijian; Chen, Zhong; Cheng, Hang; Zheng, Jinxin; Li, Duoyun; Deng, Xiangbin; Pan, Weiguang; Yang, Weizhi; Deng, Qiwen

    2014-07-01

    Genome level analysis of bacterial strains provides information on genetic composition and resistance mechanisms to clinically relevant antibiotics. To date, whole genome characterization of linezolid-resistant Enterococcus faecalis isolated in the clinic is lacking. In this study, we report the entire genome sequence, genomic characteristics and virulence factors of a pathogenic E. faecalis strain, DENG1. Our results showed considerable differences in genomic characteristics and virulence factors compared with other E. faecalis strains (V583 and OG1RF). The genome of this LZD-resistant E. faecalis strain can be used as a reference to study the mechanism of LZD resistance and the phylogenetic relationship of E. faecalis strains worldwide.

  5. Disc-diffusion and PCR detection of methicillin resistance in environmental airborne strains of Staphylococcus spp..

    PubMed

    Wolny-Koładka, Katarzyna; Lenart-Boroń, Anna; Kasprowicz, Andrzej

    2014-01-01

    The aim of this study was to assess the species composition of airborne Staphylococcus spp. in public premises, to determine the methicillin resistance of the isolates and the prevalence of mecA gene, determining resistance to β-lactams. In total 65 Staphylococcus strains were isolated from 54 sites. Four strains exhibited phenotypic methicillin resistance, while the presence of mecA gene was found in 11 strains. The results of both assays were compared, showing that the phenotypic tests revealed methicillin resistance only in 36% of the examined samples. This study revealed high species diversity among airborne Staphylococcus spp. population, which consists of multidrug resistant strains.

  6. 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

  7. 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

  8. Effect of Ventilated Caging on Water Intake and Loss in 4 Strains of Laboratory Mice.

    PubMed

    Nicolaus, Mackenzie L; Bergdall, Valerie K; Davis, Ian C; Hickman-Davis, Judy M

    2016-01-01

    Food availability, temperature, humidity, strain, and caging type all affect water consumption by mice. Measurement of transepidermal water loss (TEWL) is a new technique for the quantification of water turnover in mice. To understand water turnover in common strains of adult mice, male and female SCID, SKH, C57BL/6, and FVB mice were housed in same-sex groups of 5 animals in static cages or IVC. Body weight, TEWL, urine osmolality, and water consumption of mice and intracage temperature and humidity were measured every 48 h for comparison. Static cages were monitored for 7 d and IVC for 14 d before cage change. Female SCID, FVB, and C57 mice drank less water than did their male counterparts. Male and female SCID, SKH, and FVB mice in IVC drank less water and had higher urine osmolality than did those in static cages. In SCID and SKH mice, TEWL paralleled water consumption. C57 mice in static cages drank less water, had lower urine osmolality, and had less TEWL than did those in IVC. Temperature and humidity within the cage was higher than the macroenvironmental levels for all housing conditions, mouse strains, and sexes. Temperatures within IVC ranged from 76.6 to 81.4 °F compared with 69±0.4 °F in the room. Humidity within IVC ranged from 68% to 79% compared with 27.o%±2.7% within the room. These data demonstrate that mouse strain and housing conditions significantly influence water balance and indicate that macroenvironmental measurements do not always reflect the intracage environment. PMID:27657706

  9. Pathogenicity and genetic variation of 3 strains of Corynebacterium bovis in immunodeficient mice.

    PubMed

    Dole, Vandana S; Henderson, Kenneth S; Fister, Richard D; Pietrowski, Michael T; Maldonado, Geomaris; Clifford, Charles B

    2013-07-01

    Corynebacterium bovis has been associated with hyperkeratotic dermatitis and acanthosis in mice. We studied 3 different strains of C. bovis: one previously described to cause hyperkeratotic dermatitis (HAC), one that infected athymic nude mice without leading to the classic clinical signs, and one of bovine origin (ATCC 7715). The 3 strains showed a few biochemical and genetic differences. Immunodeficient nude mice were housed in 3 independent isolators and inoculated with pure cultures of the 3 strains. We studied the transmission of these C. bovis studies to isolator-bedding and contact sentinels housed for 5 to 12 wk in filter-top or wire-top cages in the respective isolators. Using a 16S rRNA-based qPCR assay, we did not find consistent differences in growth and transmission among the 3 C. bovis strains, and neither the incidence nor severity of hyperkeratosis or acanthosis differed between strains. Housing in filter-top compared with wire-top cages did not alter the morbidity associated with any of the strains. Our findings confirmed the variability in the gross and histologic changes associated with C. bovis infection of mice. Although bacteriology was a sensitive method for the detection of Corynebacterium spp., standard algorithms occasionally misidentified C. bovis and several related species. Our study demonstrates that PCR of skin swabs or feces is a sensitive and specific method for the detection of C. bovis infection in mice. An rpoB-based screen of samples from North American vivaria revealed that HAC is the predominant C. bovis strain in laboratory mice. PMID:23849444

  10. 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

  11. 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

  12. 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.

  13. Enterococcus faecalis as multidrug resistance strains in clinical isolates in Imam Reza Hospital in Kermanshah, Iran.

    PubMed

    Mohammadi, F; Ghafourian, S; Mohebi, R; Taherikalani, M; Pakzad, I; Valadbeigi, H; Hatami, V; Sadeghifard, N

    2015-01-01

    The current study aimed to investigate the prevalence of vancomycin-resistant Enterococcus in E. faecalis and E. faecium and antimicrobial susceptibility patterns, then dominant genes responsible for vancomycin resistance were determined. For this propose, 180 clinical isolates of Enterococcus were subjected for identification and antibiotic susceptibility assay. Then, the gene responsible vancomycin resistant strains were determined. The results demonstrated the E. faecalis as a dominant Enterococcus. Resistance to erythromycin was dominant and multidrug resistance strains observed in E. faecalis. vanA was responsible for vancomycin resistance. In conclusion, a high rate of resistance to antibiotics in Enterococcus is clearly problematic, and a novel strategy is needed to decrease resistance in Enterococcus.

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

    PubMed Central

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

    1997-01-01

    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

  15. 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.

  16. Different effects of 7-nitroindazole in reserpine-induced hypolocomotion in two strains of mice.

    PubMed

    Tadaiesky, Meigy T; Andreatini, Roberto; Vital, Maria A B F

    2006-03-27

    There are a number of reasons for believing that nitric oxide participates in motor control in the striatum. Therefore, effects of neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) were studied on the reserpine model of Parkinson's disease in Swiss and C57BL/6 mice using the open-field test. Mice received reserpine (1 mg/kg administered intraperitoneally). A significant hypolocomotion was observed 24 h and 48 h after reserpine injection. The treatment with 7-nitroindazole (25 mg/kg, administered intraperitoneally, 30 min after reserpine) attenuated reserpine-induced hypolocomotion 24 h and 48 h after the treatment in Swiss mice, but not completely in C57BL/6 mice. These results suggest that nitric oxide functions as an intercellular messenger in motor circuits in the brain. Moreover, our data suggests that the comparison of such mouse strains may provide information on genetic basis for strain differences in different sensitivity to these drugs.

  17. 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

  18. The ancestor of extant Japanese fancy mice contributed to the mosaic genomes of classical inbred strains.

    PubMed

    Takada, Toyoyuki; Ebata, Toshinobu; Noguchi, Hideki; Keane, Thomas M; Adams, David J; Narita, Takanori; Shin-I, Tadasu; Fujisawa, Hironori; Toyoda, Atsushi; Abe, Kuniya; Obata, Yuichi; Sakaki, Yoshiyuki; Moriwaki, Kazuo; Fujiyama, Asao; Kohara, Yuji; Shiroishi, Toshihiko

    2013-08-01

    Commonly used classical inbred mouse strains have mosaic genomes with sequences from different subspecific origins. Their genomes are derived predominantly from the Western European subspecies Mus musculus domesticus, with the remaining sequences derived mostly from the Japanese subspecies Mus musculus molossinus. However, it remains unknown how this intersubspecific genome introgression occurred during the establishment of classical inbred strains. In this study, we resequenced the genomes of two M. m. molossinus-derived inbred strains, MSM/Ms and JF1/Ms. MSM/Ms originated from Japanese wild mice, and the ancestry of JF1/Ms was originally found in Europe and then transferred to Japan. We compared the characteristics of these sequences to those of the C57BL/6J reference sequence and the recent data sets from the resequencing of 17 inbred strains in the Mouse Genome Project (MGP), and the results unequivocally show that genome introgression from M. m. molossinus into M. m. domesticus provided the primary framework for the mosaic genomes of classical inbred strains. Furthermore, the genomes of C57BL/6J and other classical inbred strains have long consecutive segments with extremely high similarity (>99.998%) to the JF1/Ms strain. In the early 20th century, Japanese waltzing mice with a morphological phenotype resembling that of JF1/Ms mice were often crossed with European fancy mice for early studies of "Mendelism," which suggests that the ancestor of the extant JF1/Ms strain provided the origin of the M. m. molossinus genome in classical inbred strains and largely contributed to its intersubspecific genome diversity.

  19. 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

  20. 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.

  1. 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…

  2. [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

  3. A genome-wide analysis of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis Beijing genotype.

    PubMed

    Wu, Wei; Zheng, Huajun; Zhang, Lu; Wen, Zilu; Zhang, Shulin; Pei, Hao; Yu, Guohua; Zhu, Yongqiang; Cui, Zhenling; Hu, Zhongyi; Wang, Honghai; Li, Yao

    2013-09-01

    The Beijing genotype of Mycobacterium tuberculosis (MTB) is one of the most successful MTB lineages that has disseminated in the world. In China, the rate of multidrug-resistant (MDR) tuberculosis is significantly higher than the global average rate, and the Beijing genotype strains take the largest share of MDR strains. To study the genetic basis of the epidemiological findings that Beijing genotype has often been associated with tuberculosis outbreaks and drug resistance, we determined the genome sequences of four clinical isolates: two extensively drug resistant (XDR1219, XDR1221) and two multidrug resistant (WX1, WX3), using whole-genome sequencing. A large number of individual and shared SNPs of the four Beijing strains were identified. Our isolates harbored almost all classic drug resistance-associated mutations. The mutations responsible for drug resistance in the two XDR strains were consistent with the clinical quantitative drug resistance levels. COG analysis revealed that Beijing strains have significantly higher abundances of the mutations responsible for cell wall/membrane/envelope biogenesis (COG M), secondary metabolites biosynthesis, transport and catabolism (COG Q), lipid transport and metabolism (COG I) and defense mechanisms (COG V). The shared mutated genes of the four studied Beijing strains were significantly overrepresented in three DNA repair pathways. Our analyses promote the understanding of the genome polymorphism of the Beijing family strains and provide the molecular genetic basis for their wide dissemination capacity and drug resistance.

  4. Abrogation of resistance to Theiler's virus-induced demyelination in H-2b mice deficient in beta 2-microglobulin.

    PubMed

    Rodriguez, M; Dunkel, A J; Thiemann, R L; Leibowitz, J; Zijlstra, M; Jaenisch, R

    1993-07-01

    Intracerebral infection of susceptible strains of mice with Theiler's virus, a picornavirus, results in central nervous system demyelination, which is similar to multiple sclerosis. Immunogenetic experiments indicate that the MHC (H-2) and, in particular, the D region that controls class I-restricted immune responses, is an important determinant to development of demyelination. We tested whether disruption of beta 2-microglobulin (beta 2-m) would abrogate resistance to demyelinating disease normally observed in H-2b mice. All (C57BI/6 x 129)F3 mice transgenic for homozygous beta 2-m gene disruption (-/-) developed chronic demyelination after Theiler's murine encephalomyelitis virus infection, whereas none of the infected littermates with normal expression of class I MHC (beta 2-m, +/+) developed demyelination. Demyelinated lesions showed class II MHC expression, macrophages, and TNF but no class I MHC expression or CD8+ T cells. No correlation was observed between development of demyelination and delayed-type hypersensitivity responses to virus Ag. Despite the presence of demyelinating lesions, none of the infected beta 2-m (-/-) mice developed neurologic deficits. Infectious virus and virus Ag persisted in the central nervous systems of infected beta 2-m (-/-) mice but not in beta 2-m (+/+) mice. These experiments support the hypothesis that a class I immune response mediated by CD8+ T cells is important in resistance to Theiler's murine encephalomyelitis virus-induced demyelination. Development of chronic neurologic deficits as observed in immunocompetent susceptible strains of mice may be dependent on the presence of class I MHC and CD8+ T cells.

  5. 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

  6. Induction of chloramphenicol and tetracycline resistance in Flexibacter sp. strain FS-1.

    PubMed Central

    Barcak, G J; Burchard, R P

    1985-01-01

    The gliding bacterium Flexibacter sp. strain FS-1 exhibits inducible resistance to chloramphenicol (Cmr) and tetracycline (Tcr). Either chloramphenicol or tetracycline alone induced a Cmr Tcr phenotype. The resistance is apparently not plasmid encoded. PMID:3855409

  7. 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

  8. CRISPR: new horizons in phage resistance and strain identification.

    PubMed

    Barrangou, Rodolphe; Horvath, Philippe

    2012-01-01

    Bacteria have been widely used as starter cultures in the food industry, notably for the fermentation of milk into dairy products such as cheese and yogurt. Lactic acid bacteria used in food manufacturing, such as lactobacilli, lactococci, streptococci, Leuconostoc, pediococci, and bifidobacteria, are selectively formulated based on functional characteristics that provide idiosyncratic flavor and texture attributes, as well as their ability to withstand processing and manufacturing conditions. Unfortunately, given frequent viral exposure in industrial environments, starter culture selection and development rely on defense systems that provide resistance against bacteriophage predation, including restriction-modification, abortive infection, and recently discovered CRISPRs (clustered regularly interspaced short palindromic repeats). CRISPRs, together with CRISPR-associated genes (cas), form the CRISPR/Cas immune system, which provides adaptive immunity against phages and invasive genetic elements. The immunization process is based on the incorporation of short DNA sequences from virulent phages into the CRISPR locus. Subsequently, CRISPR transcripts are processed into small interfering RNAs that guide a multifunctional protein complex to recognize and cleave matching foreign DNA. Hypervariable CRISPR loci provide insights into the phage and host population dynamics, and new avenues for enhanced phage resistance and genetic typing and tagging of industrial strains.

  9. Immunological variation between inbred laboratory mouse strains: points to consider in phenotyping genetically immunomodified mice.

    PubMed

    Sellers, R S; Clifford, C B; Treuting, P M; Brayton, C

    2012-01-01

    Inbred laboratory mouse strains are highly divergent in their immune response patterns as a result of genetic mutations and polymorphisms. The generation of genetically engineered mice (GEM) has, in the past, used embryonic stem (ES) cells for gene targeting from various 129 substrains followed by backcrossing into more fecund mouse strains. Although common inbred mice are considered "immune competent," many have variations in their immune system-some of which have been described-that may affect the phenotype. Recognition of these immune variations among commonly used inbred mouse strains is essential for the accurate interpretation of expected phenotypes or those that may arise unexpectedly. In GEM developed to study specific components of the immune system, accurate evaluation of immune responses must take into consideration not only the gene of interest but also how the background strain and microbial milieu contribute to the manifestation of findings in these mice. This article discusses points to consider regarding immunological differences between the common inbred laboratory mouse strains, particularly in their use as background strains in GEM.

  10. Differences in correlation of mRNA gene expression in mice sensitive and resistant to radiation-induced pulmonary fibrosis

    SciTech Connect

    Johnston, C.J.; Piedboeuf, B.; Finkelstein, J.N.; Baggs, R.; Rubin, P.

    1995-05-01

    Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The purpose of this study was to determine if extracellular matrix protein and transforming growth factor {beta} mRNA expression are altered late in the course of pulmonary fibrosis after irradiation, and then to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Radiation-sensitive (C57BL/6) and radiation-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabeled cDNA probes for collagens I, III and IV, fibronectin, and transforming growth factor {beta}{sub 1} and {beta}{sub 3}. Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceralde-hyde-3-phosphate dehydrogenase. Alterations in mRNA abundance were observed in the sensitive mice at all times, while levels in the resistant mice were unaffected until 26 weeks after irradiation. The relationship between extracellular matrix protein per se and increased mRNA abundance suggests that late matrix protein accumulation may be a function of gene expression. Differences in levels of transforming growth factor {beta}mRNA may lead to strain-dependent variation in fibrotic response and may also contribute to the radiation-induced component of pulmonary fibrosis. 32 refs., 5 figs.

  11. Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration.

    PubMed

    Romanova, Elena V; Rubakhin, Stanislav S; Ossyra, John R; Zombeck, Jonathan A; Nosek, Michael R; Sweedler, Jonathan V; Rhodes, Justin S

    2015-12-01

    Neurochemical differences in the hypothalamic-pituitary axis between individuals and between ages may contribute to differential susceptibility to cocaine abuse. This study measured peptide levels in the pituitary gland (Pit) and lateral hypothalamus (LH) in adolescent (age 30 days) and adult (age 65 days) mice from four standard inbred strains, FVB/NJ, DBA/2J, C57BL/6J, and BALB/cByJ, which have previously been characterized for acute locomotor responses to cocaine. Individual peptide profiles were analyzed using mass spectrometric profiling and principal component analysis. Sequences of assigned peptides were verified by tandem mass spectrometry. Principal component analysis classified all strains according to their distinct peptide profiles in Pit samples from adolescent mice, but not adults. Select pro-opiomelanocortin-derived peptides were significantly higher in adolescent BALB/cByJ and DBA/2J mice than in FVB/NJ or C57BL/6J mice. A subset of peptides in the LH, but not in the Pit, was altered by cocaine in adolescents. A 15 mg/kg dose of cocaine induced greater peptide alterations than a 30 mg/kg dose, particularly in FVB/NJ animals, with larger differences in adolescents than adults. Neuropeptides in the LH affected by acute cocaine administration included pro-opiomelanocortin-, myelin basic protein-, and glutamate transporter-derived peptides. The observed peptide differences could contribute to differential behavioral sensitivity to cocaine among strains and ages. Peptides were measured using mass spectrometry (MALDI-TOF) in individual lateral hypothalamus and pituitary samples from four strains and two ages of inbred mice in response to acute cocaine administration. Principal component analyses (PCA) classified the strains according to their peptide profiles from adolescent mice, and a subset of peptides in the lateral hypothalamus was altered by cocaine in adolescents.

  12. 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.

  13. Genetically determined difference in the antiviral action of alpha/beta interferon in cells from mice resistant or susceptible to herpes simplex virus type 2.

    PubMed

    Ellermann-Eriksen, S; Justesen, J; Mogensen, S C

    1986-09-01

    Resistance of mice to infection with herpes simplex virus type 2 (HSV-2) is genetically determined. Embryonic cells from susceptible BALB/c and resistant C57BL/6 mice were equally sensitive to infection with HSV-2 as judged by plaque area, plaquing efficiency, endpoint titration and virus yield. Cells from C57BL/6 mice showed a higher sensitivity than cells from BALB/c mice to the protective action of two preparations of alpha/beta interferon against challenge with HSV-2. This was evident both from c.p.e. inhibition and yield reduction experiments. The difference in sensitivity was dependent on virus dose and was greatest (up to 50-fold) with low virus doses. An analysis of the genetics of the alpha/beta interferon sensitivity in cells from embryos of parental mice and embryos derived from reciprocal matings between HSV-2-resistant and -susceptible mice suggested that interferon sensitivity is inherited as a co-dominant autosomal trait. The induction of the interferon-induced enzyme 2'-5'-oligoadenylate synthetase was also different in cells from the two mouse strains, since significant levels were only detected in cells from C57BL/6 mice. It is suggested that differential interferon sensitivity of cells from HSV-2-resistant and -susceptible mice might be a factor of importance for the course of the infection.

  14. Bacterial antibiotic resistance: frequency of gentamicin-resistant strains of Escherichia coli in the fecal microflora of commercial turkeys.

    PubMed

    Dubel, J R; Zink, D L; Kelley, L M; Naqi, S A; Renshaw, H W

    1982-10-01

    The relationship of subtherapeutic feeding and parenteral injection of antibiotics to the presence of antibiotic resistant strains of Escherichia coli in the fecal microflora of commercial turkeys has been investigated. Cloacal swabs collected from 137 commercial turkeys were examined for E coli resistant to gentamicin. Gentamicin-resistant E coli organisms were isolated and tested for resistance to ampicillin, chloramphenicol, kanamycin, streptomycin, and tetracycline. Strains of E coli resistant to gentamicin were identified in 118 of 137 (86.1%) specimens evaluated. There were 5 different antibiotic resistance patterns exhibited by the gentamicin-resistant strains of E coli. All strains showed a common antibiotic resistance pattern of gentamicin, kanamycin, and streptomycin. The results of the antibiotic susceptibility tests were compared to the known history of antibiotic usage in each flock. There was no significant correlation between the use of subtherapeutic concentrations of antibiotics and the frequency of gentamicin resistant E coli. However, the frequency of gentamicin-resistant E coli was closely related to the age of the bird, with birds less than 12 weeks of age being most likely to harbor E coli resistant to gentamicin. This age-dependent frequency of gentamicin-resistant E coli was associated with the common practice of dipping eggs in gentamicin and injecting newly hatched poults with gentamicin, but not with the feeding of subtherapeutic concentrations of antibiotics.

  15. Radiation-induced pulmonary endothelial dysfunction and hydroxyproline accumulation in four strains of mice

    SciTech Connect

    Ward, W.F.; Sharplin, J.; Franko, A.J.; Hinz, J.M. )

    1989-10-01

    C57BL mice exposed to 14 Gy of whole-thorax irradiation develop significant histologic lung fibrosis within 52 weeks, whereas CBA and C3H mice do not exhibit substantial fibrosis during this time. The purpose of the present study was to determine whether this strain-dependent difference in radiation histopathology is associated with genetic differences in pulmonary endothelial metabolic activity or in endothelial radioresponsiveness. C57BL/6J, C57BL/10J, CBA/J, and C3H/HeJ mice were sacrificed 12 weeks after exposure to 0 or 14 Gy of 300-kV X rays to the whole thorax. Lung angiotensin converting enzyme (ACE) activity and plasminogen activator (PLA) activity were measured as indices of pulmonary endothelial function; and lung hydroxyproline (HP) content served as an index of pulmonary fibrosis. Lung ACE and PLA activities in sham-irradiated C57BL/6J and CB57BL/10J mice were only half as high as those in sham-irradiated CBA/J and C3H/HeJ mice. Exposure to 14 Gy of X rays produced a slight but nonsignificant reduction in lung ACE and PLA activity in the C57BL strains, and a significant reduction in the CBA/J and C3H/HeJ mice. Even after 14 Gy, however, lung ACE and PLA activities in CBA/J and C3H/HeJ mice were higher than those in sham-irradiated C57BL/6J and C57BL/10J mice. Lung HP content in all four strains increased significantly after irradiation, but this increase was accompanied by an increase in lung wet weight. As a result, HP concentration (per milligram wet weight) remained constant or increased slightly in both C57BL strains and actually decreased in the CBA/J and C3H/HeJ mice. These data demonstrate significant genetic differences in both intrinsic pulmonary endothelial enzyme activity and endothelial radioresponsiveness among the four strains of mice.

  16. 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.

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

    PubMed Central

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

    2016-01-01

    The emergence of ceftriaxone-resistant Neisseria gonorrhoeae is 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 in Neisseria 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 in penA (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 mutated penA gene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutated ftsX increased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, while pilM, pilN, and pilQ were 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 of Neisseria gonorrhoeae to ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry. PMID:26787702

  18. 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

  19. Variability in Prevalence of Helicobacter pylori Strains Resistant to Clarithromycin and Levofloxacin in Southern Poland

    PubMed Central

    Karczewska, Elżbieta; Klesiewicz, Karolina; Skiba, Iwona; Wojtas-Bonior, Izabela; Sito, Edward; Czajecki, Krzysztof; Zwolińska-Wcisło, Małgorzata; Budak, Alicja

    2012-01-01

    Background. An increasing resistance of Helicobacter pylori strains to antimicrobial agents is the serious therapeutic problem. The aim of this study was to compare the primary and secondary resistance of H. pylori strains isolated between 2006–2008 (data published) and 2009–2011 to clarithromycin and levofloxacin. Material and Methods. 220 dyspeptic patients (153 before treatment, 67 after), were enrolled in the study. 51 H. pylori strains were isolated. MIC values of clarithromycin and levofloxacin were determined by the E-test method. The statistical analysis was conducted with the χ2 test with Yates correction at the 0.05 significance level (P ≤ 0.05). Results. Between 2006 and 2008, 34% (39/115) of H. pylori strains were resistant to clarithromycin (primary 21% (19/90), secondary 80% (20/25)). 5% (6/115) of strains were resistant to levofloxacin (primary 2% (2/90), secondary 16% ((4/25); data published) Between 2009–2011, 22% (11/51) of H. pylori strains were resistant to clarithromycin (primary 19% (8/43), secondary 38% (3/8)). 16% (8/51) of strains were resistant to levofloxacin (primary 12% (5/43), secondary 38% (3/8)). Conclusion. The present study has shown the increasing amount of resistant H. pylori strains isolated from patients in Southern Poland to levofloxacin and decreasing number of resistant strains to clarithromycin. PMID:22693490

  20. Variability in Prevalence of Helicobacter pylori Strains Resistant to Clarithromycin and Levofloxacin in Southern Poland.

    PubMed

    Karczewska, Elżbieta; Klesiewicz, Karolina; Skiba, Iwona; Wojtas-Bonior, Izabela; Sito, Edward; Czajecki, Krzysztof; Zwolińska-Wcisło, Małgorzata; Budak, Alicja

    2012-01-01

    Background. An increasing resistance of Helicobacter pylori strains to antimicrobial agents is the serious therapeutic problem. The aim of this study was to compare the primary and secondary resistance of H. pylori strains isolated between 2006-2008 (data published) and 2009-2011 to clarithromycin and levofloxacin. Material and Methods. 220 dyspeptic patients (153 before treatment, 67 after), were enrolled in the study. 51 H. pylori strains were isolated. MIC values of clarithromycin and levofloxacin were determined by the E-test method. The statistical analysis was conducted with the χ(2) test with Yates correction at the 0.05 significance level (P ≤ 0.05). Results. Between 2006 and 2008, 34% (39/115) of H. pylori strains were resistant to clarithromycin (primary 21% (19/90), secondary 80% (20/25)). 5% (6/115) of strains were resistant to levofloxacin (primary 2% (2/90), secondary 16% ((4/25); data published) Between 2009-2011, 22% (11/51) of H. pylori strains were resistant to clarithromycin (primary 19% (8/43), secondary 38% (3/8)). 16% (8/51) of strains were resistant to levofloxacin (primary 12% (5/43), secondary 38% (3/8)). Conclusion. The present study has shown the increasing amount of resistant H. pylori strains isolated from patients in Southern Poland to levofloxacin and decreasing number of resistant strains to clarithromycin.

  1. Resistance patterns of Campylobacter spp. strains isolated from poultry carcasses in a big Swiss poultry slaughterhouse.

    PubMed

    Frediani-Wolf, V; Stephan, R

    2003-12-31

    The aim of this study was to determine resistance patterns of strains of Campylobacter spp. isolated from poultry carcasses in one of the two big Swiss poultry slaughterhouses. A variety of antibiotics with clinical relevance in human and/or in veterinary medicine was tested. In addition, the results of the disc diffusion method, E-test and microdilution broth methods were compared. Of the 195 Campylobacter jejuni strains isolated from 195 poultry carcasses from 21 flocks, 134 strains were susceptible in vitro to all tested antibiotics. Sixty-one strains (31.3%, from eight flocks) showed resistance. Forty-one strains were resistant to a single antibiotic-34 to streptomycin, 6 to ampicillin and 1 to ciprofloxacin. Eighteen strains (from two flocks) showed combined resistance to erythromycin and streptomycin, two strains to ciprofloxacin and streptomycin. None of the isolates was resistant to tetracycline. The data of this first study in Switzerland show a favourable resistance situation for C. jejuni strains against erythromycin, tetracycline and ciprofloxacin. The disc diffusion method was found to be a reliable and easy tool for monitoring the prevalence of resistant C. jejuni strains. For surveillance of changes in the susceptibility concentration levels to antimicrobial agents, however, a MIC method should be used. Further investigations along the whole poultry production chain (farm, slaughterhouse and retail levels) are now necessary in order to confirm the resistance situation.

  2. 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

  3. Levofloxacin resistance of Helicobacter pylori strains isolated from patients in southern Poland, between 2006-2012.

    PubMed

    Karczewska, Elzbieta; Klesiewicz, Karolina; Wojtas-Bonior, Izabela; Skiba, Iwona; Sito, Edward; Czajecki, Krzysztof; Zwolińska-Wcisło, Małgorzata; Budak, Alicja

    2014-01-01

    An increasing resistance of Helicobacter pylori (H. pylori) to antimicrobial agents leads to the need of regional monitoring of the prevalence resistant strains (according to the Maastricht/Florence consensus report, 2012). The aim of the study was to assess the resistance to levofloxacin of H. pylori strains isolated from adult patients of Małopolska region in Poland. Bioptates taken from gastric mucosa during gastroscopy constituted the material for the study. Two hundred ten H. pylori strains were isolated from 811 patients. A majority of strains (171) came from patients before the treatment of H. pylori infections while the remaining 39 strains were isolated from patients after the failed therapy. Susceptibility of H. pylori to levofloxacin was determined by strips impregnated with antibiotic gradient (E-test, bioMerieux). The obtained minimum inhibitory concentration (MIC) values ranged from 0.002 mg/L to 32 mg/L. The percentage of strains resistant to levofloxacin amounted to 8.10% (17/210). Among the group of strains isolated from patients before the treatment, 5.85% (10/171) of H. pylori strains were resistant to levofloxacin. In the group of strains isolated from patients after the treatment 17.95% (7/39) of strains were resistant. The difference in the frequency of H. pylori strains resistant to levofloxacin in patients before and after the treatment of the infection due to H. pylori was statistically significant (p = 0.0297). The low percentage of H. pylori strains resistant to levofloxacin justify that the introduction of a triple therapy with levofloxacin is a good alternative in the treatment of H. pylori infections, especially in regions with high prevalence of H. pylori strains resistant to clarithromycin (> 20%).

  4. 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

  5. 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

  6. Comparison of the taxonomy, serology, drug resistance transfer, and virulence of Citrobacter freundii strains from mammals and poikilothermic hosts.

    PubMed Central

    Toranzo, A E; Cutrín, J M; Roberson, B S; Núñez, S; Abell, J M; Hetrick, F M; Baya, A M

    1994-01-01

    In this study, the phenotypic, antigenic, and virulence characteristics of 32 Citrobacter freundii strains of fish, human, and veterinary origin were comparatively analyzed. In addition, the spread of drug resistance factors by conjugation was investigated. Regardless of the source of isolation, the strains exhibited variable reactions mainly for arginine dihydrolase, ornithine decarboxylase, and fermentation of sucrose, melibiose, amygdalin, and salicin. Total fatty acid methyl ester analysis by gas chromatography proved to be useful for an intratypic differentiation within the C. freundii strains studied. In fact, although all of the isolates exhibited similar fatty acid methyl ester profiles, significant differences in the major fatty acids 16:1 and 16:0 and in the 17:0 delta region were observed between the isolates from salmonids and the remaining strains. Serological studies using agglutination tests, analysis of lipopolysaccharides (LPS), and the corresponding immunoblots with 13 antisera indicated a great antigenic diversity among the strains. Common LPS patterns were shared only by some isolates showing high cross-agglutination titers. In contrast, although all strains exhibited very similar surface protein patterns, only two common outer membrane proteins of 54 and 58 kDa were immunologically related. Infectivity trials performed in mice and rainbow trout indicated that all of the C. freundii strains were not pathogenic for mice (50% lethal dose of > 5 x 10(7)). Although the isolates displayed a low degree of virulence for trout, inoculated strains were always recovered from the survivors in pure culture.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8031079

  7. Phenotypic and genomic characterization of human coxsackievirus A16 strains with distinct virulence in mice.

    PubMed

    Han, Jian-Feng; Yu, Nan; Pan, Yu-Xian; He, Si-Jie; Xu, Li-Juan; Cao, Rui-Yuan; Li, Yue-Xiang; Zhu, Shun-Ya; Zhang, Yu; Qin, E-De; Che, Xiao-Yan; Qin, Cheng-Feng

    2014-01-22

    Human coxsackievirus A16 (CA16) infection results in hand, foot, and mouth disease (HFMD) along with other severe neurological diseases in children and poses an important public health threat in Asian countries. During an HFMD epidemic in 2009 in Guangdong, China, two CA16 strains (GD09/119 and GD09/24) were isolated and characterized. Although both strains were similar in plaque morphology and growth properties in vitro, the two isolates exhibited distinct pathogenicity in neonatal mice upon intraperitoneal or intracranial injection. Complete genome sequences of both CA16 strains were determined, and the possible virulence determinants were analyzed and predicted. Phylogenetic analysis revealed that these CA16 isolates from Guangdong belonged to the B1b genotype and were closely related to other recent CA16 strains isolated in mainland China. Similarity and bootscanning analyses of these CA16 strains detected homologous recombination with the EV71 prototype strain BrCr in the non-structural gene regions and the 3'-untranslated regions. Together, the phenotypic and genomic characterizations of the two clinical CA16 isolates circulating in China were compared in detail, and the potential amino acid residues responsible for CA16 virulence in mice were predicted. These findings will help explain the evolutionary relationship of the CA16 strains circulating in China, warranting future studies investigating enterovirus virulence.

  8. Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice.

    PubMed

    Stiedl, O; Radulovic, J; Lohmann, R; Birkenfeld, K; Palve, M; Kammermeier, J; Sananbenesi, F; Spiess, J

    1999-10-01

    The performance of C57BL/6J (6J), C57BL/6N (6N), DBA/2J (2J) and DBA/2N (2N) mice in context- and tone-dependent fear conditioning was determined 24 h after fear conditioning to evaluate and compare different behavioral measures as indices of emotional learning. Freezing, the change in activity and the size of the explored area were evaluated as behavioral parameters indicating fear. Additionally, the heart rate (HR) increase elicited by tone presentation was evaluated as an autonomic indicator of fear. During the context-dependent memory test, freezing was high only in 6J and 6N mice, whereas a drop of activity and a reduced exploratory area was measured in all strains. During the tone-dependent memory test, high freezing, low activity, reduced exploratory area and a strong HR increase were demonstrated only in 6N and 6J mice, whereas behavioral and HR changes of 2J and 2N mice were always low. In extinction tests, context- and tone-dependent freezing of 6J mice decayed significantly faster than the freezing of 6N mice, whereas in both substrains the conditioned tachycardia to tone extinguished similarly in the home cage. The data demonstrate that monitoring of additional behavioral measures besides freezing and autonomic measures is necessary to interpret differences in associative learning performance of mouse strains that could be related to a differential expression of fear.

  9. 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

  10. 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,…

  11. 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

  12. Sex and strain influence attribution of incentive salience to reward cues in mice.

    PubMed

    Dickson, Price E; McNaughton, Kathryn A; Hou, Lingfeng; Anderson, Laura C; Long, Katie H; Chesler, Elissa J

    2015-10-01

    The propensity to attribute incentive salience to reward cues, measured by Pavlovian sign-tracking, is strongly associated with addiction-related traits including cocaine self-administration, impulsivity, novelty reactivity, and novelty preference. Despite its critical role in addiction, the genetic underpinnings of incentive salience attribution and its relationship to drug addiction are unknown. Mouse genetics can be a powerful means to discover genetic mechanisms underlying this relationship. However, feasibility of genetic dissection of sign-tracking in mice is unknown as only a single study limited to male C57BL/6J mice has rigorously examined this behavior, and limited sign-tracking was observed. Highly diverse mouse populations such as the Collaborative Cross (CC) and Diversity Outbred population (DO) possess a greater range of behavioral and genetic variation than conventional laboratory strains. In the present study, we evaluated sign-tracking and the related phenotype goal-tracking in mice of both sexes from five inbred CC and DO founder strains. Male CAST/EiJ mice exhibited robust sign-tracking; male NOD, male C57BL/6J, and female A/J mice also exhibited significant sign-tracking. Male and female mice from all strains exhibited significant goal-tracking, and significant strain and sex differences were observed. Sign-tracking in males was genetically correlated with exploration of a novel environment, and heritability of sign-tracking and goal-tracking ranged from .32 to .41. These data highlight the importance of considering genetic diversity when evaluating the occurrence of specific behavioral traits in the laboratory mouse and demonstrate that the CC and DO mouse populations can be used to discover mechanisms underlying genetic relationships among sign-tracking and addiction-related behaviors. PMID:26102561

  13. Draft Genome Sequence of a Multidrug-Resistant Acinetobacter baumannii Strain from Chile

    PubMed Central

    Lopes, Bruno S.; García, Patricia; Domínguez Yévenes, Mariana; Lima, Celia; Bello-Toledo, Helia; González-Rocha, Gerardo; Amyes, Sebastian G. B.

    2015-01-01

    Acinetobacter baumannii strain Ab5 was isolated in the year 2007 in Chile, being one of the first multidrug-resistant (MDR) cases reported in the country. Here, we present the very first draft genome sequence of an MDR Chilean strain, which shows the presence of diverse resistance and acquired virulence genes. PMID:26139713

  14. Draft Genome of the Multidrug-Resistant Acinetobacter baumannii Strain A155 Clinical Isolate

    PubMed Central

    Arivett, Brock A.; Fiester, Steven E.; Ream, David C.; Centrón, Daniela; Ramírez, Maria S.; Tolmasky, Marcelo E.

    2015-01-01

    Acinetobacter baumannii is a bacterial pathogen with serious implications on human health, due to increasing reports of multidrug-resistant strains isolated from patients. Total DNA from the multidrug-resistant A. baumannii strain A155 clinical isolate was sequenced to greater than 65× coverage, providing high-quality contig assemblies. PMID:25814610

  15. Large-scale phenotyping of noise-induced hearing loss in 100 strains of mice.

    PubMed

    Myint, Anthony; White, Cory H; Ohmen, Jeffrey D; Li, Xin; Wang, Juemei; Lavinsky, Joel; Salehi, Pezhman; Crow, Amanda L; Ohyama, Takahiro; Friedman, Rick A

    2016-02-01

    A cornerstone technique in the study of hearing is the Auditory Brainstem Response (ABR), an electrophysiologic technique that can be used as a quantitative measure of hearing function. Previous studies have published databases of baseline ABR thresholds for mouse strains, providing a valuable resource for the study of baseline hearing function and genetic mapping of hearing traits in mice. In this study, we further expand upon the existing literature by characterizing the baseline ABR characteristics of 100 inbred mouse strains, 47 of which are newly characterized for hearing function. We identify several distinct patterns of baseline hearing deficits and provide potential avenues for further investigation. Additionally, we characterize the sensitivity of the same 100 strains to noise exposure using permanent thresholds shifts, identifying several distinct patterns of noise-sensitivity. The resulting data provides a new resource for studying hearing loss and noise-sensitivity in mice.

  16. 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.

  17. Phenotypic and genotypic characterization of drug-resistant Mycobacterium tuberculosis strains.

    PubMed

    Clemente, Wanessa Trindade; Soares Lima, Stella Sala; Palaci, Moises; Silva, Márcia S N; Sumnienski Rodrigues, Vivian F; Dalla Costa, Elis R; Possuelo, Lia; Cafrune, Patrícia Izquierdo; Ribeiro, Fabíola Karla; Gomes, Harisson M; Serufo, José Carlos

    2008-10-01

    Of 142 pulmonary tuberculosis patients, 76 were considered high risk for the development of resistance, and 24 were confirmed as resistant strain carriers. Resistant isoniazid strains presented a high frequency of katG and ahpC mutations (90%) correlated with an MIC >4 microg/mL (94%). inhA mutations were not seen. rpoB mutations were identified in 78.6% of rifampicin-resistant strains, usually in codon 531 (72.7%), and 75% had an MIC >16 microg/mL. katG and rpoB mutations recognized 88.2% of multidrug-resistant strains and proved more efficient than the katG and rpoB mutations alone. Seventy percent of resistant pyrazinamide strains had pncA mutations between genes 136 and 188, 62.5% of them with an MIC >900 microg/mL. Pyrazinamidase inactivity was not an efficient resistance marker because 60% of pncA-mutated strains maintained enzymatic activity despite displaying good correlation with high resistance levels. Resistant ethambutol strains had embB mutations in codon 306, with MIC >16 microg/mL.

  18. 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

  19. 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

  20. Morphologic analysis of spontaneous teratocarcinogenesis in developing testes of strain 129/Sv-ter mice.

    PubMed

    Rivers, E N; Hamilton, D W

    1986-08-01

    Spontaneous teratocarcinogenesis in the mouse testis begins during the early stages of gonad differentiation. Using inbred strain 129/Sv-ter mice which are highly susceptible to these tumors, the authors have examined the morphologic features of the testis during the gestational period defined from Day 13 through birth. Normal inbred mice (129/J) and random bred mice (Swiss Webster, SW) were used as control groups. Serially sectioned gonads were evaluated at the light- and electron-microscopic levels for histologic changes. In agreement with studies by other workers, embryonal carcinoma cells (ECCs) were observed in tumor-susceptible mice. Cellular arrangements varied from vesicular to nodular. Cell death within advanced tumors was labeled "apoptosis" (shrinkage necrosis). Also encountered were syncytial arrangements of gonocytes (atypical gonocytes), which were present in all animal groups. The significance of atypical gonocytes in relation to degeneration and preneoplasia is addressed.

  1. Role of mouse hepatitis virus (MHV) receptor murine CEACAM1 in the resistance of mice to MHV infection: studies of mice with chimeric mCEACAM1a and mCEACAM1b.

    PubMed

    Hirai, Asuka; Ohtsuka, Nobuhisa; Ikeda, Toshio; Taniguchi, Rie; Blau, Dianna; Nakagaki, Keiko; Miura, Hideka S; Ami, Yasushi; Yamada, Yasuko K; Itohara, Shigeyoshi; Holmes, Kathryn V; Taguchi, Fumihiro

    2010-07-01

    Although most inbred mouse strains are highly susceptible to mouse hepatitis virus (MHV) infection, the inbred SJL line of mice is highly resistant to its infection. The principal receptor for MHV is murine CEACAM1 (mCEACAM1). Susceptible strains of mice are homozygous for the 1a allele of mCeacam1, while SJL mice are homozygous for the 1b allele. mCEACAM1a (1a) has a 10- to 100-fold-higher receptor activity than does mCEACAM1b (1b). To explore the hypothesis that MHV susceptibility is due to the different MHV receptor activities of 1a and 1b, we established a chimeric C57BL/6 mouse (cB61ba) in which a part of the N-terminal immunoglobulin (Ig)-like domain of the mCeacam1a (1a) gene, which is responsible for MHV receptor function, is replaced by the corresponding region of mCeacam1b (1b). We compared the MHV susceptibility of these chimeric mice to that of SJL and B6 mice. B6 mice that are homozygous for 1a are highly susceptible to MHV-A59 infection, with a 50% lethal dose (LD(50)) of 10(2.5) PFU, while chimeric cB61ba mice and SJL mice homozygous for 1ba and 1b, respectively, survived following inoculation with 10(5) PFU. Unexpectedly, cB61ba mice were more resistant to MHV-A59 infection than SJL mice as measured by virus replication in target organs, including liver and brain. No infectious virus or viral RNA was detected in the organs of cB61ba mice, while viral RNA and infectious virus were detected in target organs of SJL mice. Furthermore, SJL mice produced antiviral antibodies after MHV-A59 inoculation with 10(5) PFU, but cB61ba mice did not. Thus, cB61ba mice are apparently completely resistant to MHV-A59 infection, while SJL mice permit low levels of MHV-A59 virus replication during self-limited, asymptomatic infection. When expressed on cultured BHK cells, the mCEACAM1b and mCEACAM1ba proteins had similar levels of MHV-A59 receptor activity. These results strongly support the hypothesis that although alleles of mCEACAM1 are the principal determinants of

  2. 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

    2015-08-14

    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.

  3. Strain-dependent lung tumor formation in mice transplacentally exposed to 3-methylcholanthrene and post-natally exposed to butylated hydroxytoluene.

    PubMed

    Gressani, K M; Leone-Kabler, S; O'Sullivan, M G; Case, L D; Malkinson, A M; Miller, M S

    1999-11-01

    The carcinogenic effects of in utero exposure to 3-methylcholanthrene (MC) have been demonstrated in the tumor-resistant C57BL/6 (B6) and DBA (D2) strains of mice. In this study, we determined the effects of in utero exposure to MC in BALB/c mice, a strain which demonstrates greater susceptibility to lung tumor induction, and compared our findings with those previously found in [D2xB6D2F(1)]F(2) mice. In addition, we assessed the molecular pathogenesis of the chemically induced tumors and examined the effects of the putative lung tumor promoter butylated hydroxytoluene (BHT) in BALB/c mice. BALB/c mice were treated on day 17 of gestation with 5, 15 or 45 mg/kg MC and 6 weeks after birth with BHT for 6 consecutive weeks. Mice were killed at 6 months of age. Ki-ras, p16Ink4a and p19ARF gene loci were amplified from paraffin-embedded lung tumor tissue and screened for the presence of point mutations via allele-specific oligonucleotide hybridization and single strand conformation polymorphism (SSCP) analyses. Ki-ras point mutations were found in 56% (20/36) of BALB/c lung tumors, with 33% (2/6) of the hyperplasias, 58% (10/19) of the adenomas and 73% (8/11) of the carcinomas exhibiting point mutations at this gene locus. Similar incidences of Ki-ras mutations were previously found following transplacental exposure of [D2xB6D2F(1)]F(2) mice to MC and treatment of adult A/J mice with urethane. Interestingly, a strain-dependent difference was observed in the mutational spectrum. Sixty-two and 38% of the lung lesions in BALB/c mice exhibited G-->C and G-->T transversions, respectively, in contrast to the 13 and 84% incidences previously observed in [D2xB6D2F(1)]F(2) mice. SSCP analysis of the tumor suppressor gene p16Ink4a showed a 6% incidence of point mutations, consistent with that found in [D2xB6D2F(1)]F(2) mice. No mutations were found in exon 1beta of the p19ARF gene of either strain. BHT, a lung tumor promoter in adult mice, had no statistically significant effects

  4. Genetic analyses of the antibiotic resistance of Bifidobacterium bifidum strain Yakult YIT 4007.

    PubMed

    Sato, Takashi; Iino, Tohru

    2010-02-28

    Bifidobacterium bifidum strain Yakult YIT 4007 (abbreviated as B. bifidum YIT 4007) is a commercial strain and resistant to erythromycin, neomycin, and streptomycin. Resistances to these antibiotics were endowed by sequential isolation of resistant mutants from its susceptible progenitor strain YIT 4001. Comparison of nucleotide sequences of various candidate genes of both strains led us to find that B. bifidum YIT 4007 had mutations on three copies of 23S ribosomal RNA genes, an 8 bp deletion of the rluD gene for pseudouridine synthase, and a mutation on the rpsL gene for ribosomal protein S12. The responsibility of these mutations to antibiotic resistances was supported by analyses of newly isolated mutants resistant to these antibiotics. The antibiotic resistances of B. bifidum YIT 4007 were evidently acquired by mutations of the structural genes on the chromosome and not associated with mobile genetic elements like insertion sequences, phages, and plasmids.

  5. 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.

  6. Wheat grain consumption and selection by inbred and outbred strains of mice.

    PubMed

    O C, Lottes; A M, Kiszonas; E P, Fuerst; C F, Morris

    2016-10-15

    Food selection and avoidance are driven primarily by orosensory cues. Previous studies with C57BL/6J mice indicated marked differences in selection and consumption of individual grains of different wheat varieties when presented in binary mixtures. The present study examined the patterns of mouse grain selection across four strains of laboratory mice: two inbred, BALB/c and C57BL/6J, and two outbred, Swiss-Webster and CD1. Four pairs of wheat varieties that were known to vary a priori for consumption preference or seed coat ('bran') color were tested. Two variety pairs were near-isogenic (>98% similar) with contrasting red and white seed coat coloration/pigmentation. All four mice strains exhibited similar preferences between wheat variety pairs, whereas consumption was not highly related to mouse body weight. This result indicates a more generalized phenomenon regarding how mice select and then consume individual wheat grains. The study supported the continued use of C57BL/6J as an effective strain model system to study food perception. PMID:27436794

  7. γδ T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice.

    PubMed

    Mehta, Pooja; Nuotio-Antar, Alli Martina; Smith, C Wayne

    2015-01-01

    γδ T cells are resident in AT and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5 to 10 week milk HFD. The HFD resulted in significant increases in CD44(hi), CD62L(lo), and TNF-α(+) γδ T cells in eAT of WT mice. Mice deficient in all γδ T cells (TCRδ(-/-)) or only Vγ4 and Vγ6 subsets (Vγ4/6(-/-)) were compared with WT mice with regard to proinflammatory cytokine production and macrophage accumulation in eAT. Obesity among these mouse strains did not differ, but obese TCRδ(-/-) and Vγ4/6(-/-) mice had significantly reduced eAT expression of F4/80, a macrophage marker, and inflammatory mediators CCL2 and IL-6 compared with WT mice. Obese TCRδ(-/-) mice had significantly reduced CD11c(+) and TNF-α(+) macrophage accumulation in eAT after 5 and 10 weeks on the HFD, and obese Vγ4/6(-/-) mice had significantly increased CD206(+) macrophages in eAT after 5 weeks on the diet and significantly reduced macrophages after 10 weeks. Obese TCRδ(-/-) mice had significant reductions in systemic insulin resistance and inflammation in liver and skeletal muscle after longer-term HFD feeding (10 and 24 weeks). In vitro studies revealed that isolated γδ T cells directly stimulated RAW264.7 macrophage TNF-α expression but did not stimulate inflammatory mediator expression in 3T3-L1 adipocytes. These findings are consistent with a role for γδ T cells in the proinflammatory response that accompanies diet-induced obesity.

  8. 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

  9. Effects of mescaline and amphetamine on simultaneous visual discrimination in two inbred strains of mice.

    PubMed

    Castellano, C

    1979-03-29

    The effects of mescaline and amphetamine were investigated in BALB/cJ (BALB) and C57BL/6J (C57) mice using the five-choice Yerkes--Thompson Bryant--Bovet-Nitti apparatus for patterns discrimination. Two sets of experiments were carried out. In the first set, pretrial administration of mescaline (5, 10, and 20 mg/kg) was followed by performance improvements in the C57 mice, while performances of the BALB strain were impaired by the treatment, as compared with those of the saline-injected (4 ml/kg) controls. The pretrial administration of amphetamine (0.1, 0.25, and 0.5 mg/kg) improved performances of both strains. In a second set of experiments, the same effects as in the pretrial experiments were observed in both strains following administration of mescaline (20 mg/kg) and amphetamine (0.5 mg/kg) immediately after each experimental session. No effect was evident when the drugs were injected 2 h after training, suggesting that effects of the pretrial treatments were due to influences of mescaline and amphetamine on the consolidation processes of the two strains of mice tested.

  10. Improved reporter strain for monitoring Cre recombinase-mediated DNA excisions in mice

    PubMed Central

    Mao, Xiaohong; Fujiwara, Yuko; Orkin, Stuart H.

    1999-01-01

    Effective use of conditional Cre recombinase-loxP gene modification requires Cre-expressing mouse strains with defined patterns of expression. To assess the in vivo functionality of Cre-expressing mice, we have engineered an improved reporter strain for monitoring Cre-mediated excisions. The β-galactosidase-neomycin phosphotransferase fusion gene (βgeo)-trapped ROSA26 locus was modified by gene targeting such that βgeo is expressed only after Cre-mediated excision of loxP-flanked DNA sequences. βgeo from the excised ROSA26 allele is expressed ubiquitously in embryos and adult mice. By mating the reporter strain with Cre-expressing transgenic mice, we have shown that the loxP-flanked ROSA26 allele is accessible to Cre during early embryogenesis, as well as in a specific hematopoietic lineage (T lymphocytes). This improved reporter strain should facilitate monitoring in vivo Cre-mediated excision events in a variety of experimental contexts. PMID:10220414

  11. 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.

  12. Diversity assessment of heat resistance of Listeria monocytogenes strains in a continuous-flow heating system.

    PubMed

    van der Veen, Stijn; Wagendorp, Arjen; Abee, Tjakko; Wells-Bennik, Marjon H J

    2009-05-01

    Listeria monocytogenes is a foodborne pathogen that has the ability to survive relatively high temperatures compared with other nonsporulating foodborne pathogens. This study was performed to determine whether L. monocytogenes strains with relatively high heat resistances are adequately inactivated in a high-temperature, short-time pasteurization process (72 degrees C for 15 s). To obtain heat-resistant strains, 48 strains were exposed to 55 degrees C for up to 3 h. The energy of activation constant and inactivation constant of strains that survived best (strains 1E and NV8) were subsequently determined in a continuous-flow-through system. Strain Scott A was taken along as a reference. The 3 strains were cultured in whole milk and in brain heart infusion broth at 30 and 7 degrees C. Strains 1E and NV8 were significantly more heat resistant than was strain Scott A after growth in brain heart infusion broth at 30 degrees C and after growth in milk at 7 degrees C. From the inactivation parameters, it was calculated that exposure to high-temperature, short-time pasteurization (72 degrees C for 15 s) will result in 12.1-, 14.2-, and 87.5-log reductions for the strains 1E, NV8, and Scott A, respectively. These results demonstrate that industrial pasteurization conditions suffice to inactivate the most heat-resistant L. monocytogenes strains tested in this study.

  13. Enhancement of antibacterial resistance of neutropenic, bone marrow-suppressed mice by interleukin-1 alpha.

    PubMed Central

    McIntyre, K W; Unowsky, J; DeLorenzo, W; Benjamin, W

    1989-01-01

    The effect of recombinant human interleukin-1 alpha (IL-1) on the resistance of normal and bone marrow-suppressed mice against bacterial infection was evaluated. IL-1 induced neutrophilia and enhanced the resistance of normal mice against acute, systemic intraperitoneal infection with Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus. Mice with cyclophosphamide-induced bone marrow suppression were neutropenic and exhibited increased susceptibility to infection. Treatment of neutropenic C57BL/6 and C3H/HeJ mice with IL-1 before infection accelerated recovery of peripheral neutrophil counts and stimulated resistance against infection. Increases in neutrophils and enhancement of resistance induced by IL-1 were both dose and time dependent. Both neutrophilia and augmented resistance to infection were eliminated by a second dose of cyclophosphamide administered during the IL-1 treatments. Bone marrow-suppressed mice treated with IL-1 showed, at 4 h postinfection, greater increases in peripheral blood neutrophils and in numbers of peritoneal exudate neutrophils than suppressed mice treated with vehicle. The data suggest that the IL-1-stimulated recovery of myelopoiesis is an important factor in the enhancement of antibacterial resistance in bone marrow-suppressed, neutropenic mice. These findings indicate that IL-1 may be efficacious in limiting the duration of the neutropenia and of the increased risk for the development of bacterial infection associated with bone marrow suppression. PMID:2783314

  14. 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

  15. Evolutionary dynamics of complex networks of HIV drug-resistant strains: the case of San Francisco.

    PubMed

    Smith, Robert J; Okano, Justin T; Kahn, James S; Bodine, Erin N; Blower, Sally

    2010-02-01

    Over the past two decades, HIV resistance to antiretroviral drugs (ARVs) has risen to high levels in the wealthier countries of the world, which are able to afford widespread treatment. We have gained insights into the evolution and transmission dynamics of ARV resistance by designing a biologically complex multistrain network model. With this model, we traced the evolutionary history of ARV resistance in San Francisco and predict its future dynamics. By using classification and regression trees, we identified the key immunologic, virologic, and treatment factors that increase ARV resistance. Our modeling shows that 60% of the currently circulating ARV-resistant strains in San Francisco are capable of causing self-sustaining epidemics, because each individual infected with one of these strains can cause, on average, more than one new resistant infection. It is possible that a new wave of ARV-resistant strains that pose a substantial threat to global public health is emerging. PMID:20075214

  16. The lung tumor promoter, butylated hydroxytoluene (BHT), causes chronic inflammation in promotion-sensitive BALB/cByJ mice but not in promotion-resistant CXB4 mice.

    PubMed

    Bauer, A K; Dwyer-Nield, L D; Hankin, J A; Murphy, R C; Malkinson, A M

    2001-12-01

    An inflammatory response accompanies the reversible pneumotoxicity caused by butylated hydroxytoluene (BHT) administration to mice. Lung tumor formation is promoted by BHT administration following an initiating agent in BALB/cByJ mice, but not in CXB4 mice. To assess the contribution of inflammation to this differential susceptibility, we quantitatively characterized inflammation after one 150 mg/kg body weight, followed by three weekly 200 mg/kg ip injections of BHT into male mice of both strains. This examination included inflammatory cell infiltrate and protein contents in bronchoalveolar lavage (BAL) fluid, cyclooxygenase (COX)-1 and COX-2 expression in lung extracts, and PGE(2) and PGI(2) production by isolated bronchiolar Clara cells. BAL macrophage and lymphocyte numbers increased in BALB mice (P<0.0007 and 0.02, respectively), as did BAL protein content (P<0.05), COX-1 and COX-2 expression (P<0.05 for each), and PGI(2) production (P<0.05); conversely, these indices were not perturbed by BHT in CXB4 mice. BALB mice fed aspirin (400 mg/kg of chow) for two weeks prior to BHT treatment had reduced inflammatory cell infiltration. Our results support a hypothesis that resistance to BHT-induced inflammation in CXB4 mice accounts, at least in part, for the lack of effect of BHT on lung tumor multiplicity in this strain.

  17. Microarray based comparative genotyping of gentamicin resistant Escherichia coli strains from food animals and humans.

    PubMed

    Szmolka, Ama; Anjum, Muna F; La Ragione, Roberto M; Kaszanyitzky, Eva J; Nagy, Béla

    2012-04-23

    Recent data from the European and Hungarian Antimicrobial Resistance Monitoring Systems have indicated that the routine use of gentamicin in human and veterinary medicine frequently leads to the selection of gentamicin resistance in Escherichia coli. The aim of this study was to provide molecular characterization of gentamicin resistance in clinical and commensal E. coli strains representing humans and food producing animals by genotyping for antimicrobial resistance and virulence using a miniaturized microarray. All 50 strains tested proved to be multidrug resistant defined as resistance to three or more antimicrobial classes. Antimicrobial resistances genes such as aadA1-like, strB, bla(TEM), sul1 and tet(A) or tet(B), and corresponding phenotypes (streptomycin-, ampicillin-, sulfamethoxazole- and tetracycline resistance) were detected in >50% of isolates regardless of the host or clinical background. However, certain genes encoding gentamicin resistance such as aac(6')-Ib and ant(2″)-Ia as well as catB3-like genes for phenicol resistance were only detected in human isolates. Among virulence genes, the increased serum survival gene iss was predominant in all host groups. Although the majority of gentamicin resistant E. coli strains were characterized by diverse antimicrobial resistance, and virulence gene patterns, accentuated links between catB3-like, aac(6')-Ib, bla(CTX-M-1) and sat genes could be detected in human strains. Further resistance/virulence gene associations (tet(A) with iroN and iss) were detected in poultry strains. In conclusion, the simultaneous characterization of antimicrobial resistance and virulence genotypes of representative clinical and commensal strains of E. coli should be useful for the identification of emerging genotypes with human and or animal health implications.

  18. Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie.

    PubMed

    Espinosa, Juan Carlos; Herva, María Eugenia; Andréoletti, Olivier; Padilla, Danielle; Lacroux, Caroline; Cassard, Hervé; Lantier, Isabelle; Castilla, Joaquin; Torres, Juan Maria

    2009-08-01

    How susceptible pigs are to infection with sheep prions is unknown. We show, through transmission experiments in transgenic mice expressing porcine prion protein (PrP), that the susceptibility of this mouse model to bovine spongiform encephalopathy (BSE) can be enhanced after its passage in ARQ sheep, indicating that the pathogenicity of the BSE agent is modified after passage in sheep. Transgenic mice expressing porcine PrP were, nevertheless, completely resistant to infection with a broad panel of classical scrapie isolates from different sheep PrP genotypes and with different biochemical characteristics. The atypical (Nor98 like) isolate (SC-PS152) was the only scrapie isolate capable of transmission in these mice, although with a marked transmission barrier. Unexpectedly, the atypical scrapie agent appeared to undergo a strain phenotype shift upon transmission to porcine-PrP transgenic mice and acquired new strain properties, suggesting that atypical scrapie agent may exhibit different phenotypes depending on the host cellular PrP or other genetic factors.

  19. Biochemical studies on strain differences of mice in the susceptibility to nitrogen dioxide

    SciTech Connect

    Ichinose, T.; Suzuki, A.K.; Tsubone, H.; Sagai, M.

    1982-11-01

    Strain differences of mice in their susceptibility to nitrogen dioxide (NO/sub 2/) were examined by measuring the activities of antioxidative protective enzymes, and the amounts of antioxidants and lipid peroxides in lungs. Four strains of mice: ICR, BALB/c, ddy and C57BL/6 were used in this study and their LC/sub 50/ values after exposure to NO/sub 2/ for 16 hr were: 38, 49, 51 and 64 ppm, respectively. Genetic strain differences were observed in the enzyme activities, the antioxidant contents and lipid peroxide contents among these four different strains. The activities of glutathione peroxidase (GP/sub x/), glutathione S-transferase, and superoxide dismutase (SOD), and the contents of non-protein sulfyhdryls (NPSH), ..cap alpha..-tocopherol (..cap alpha..-Toc) and total lipids in lungs of the four strains were related to their LC/sub 50/, while TBA reactants in lungs of the four strains were inversely related to their LC/sub 50/. After exposure to 20 ppm NO/sub 2/ for 16 hr, the activities of the protective enzymes and the contents of NPSH decreased, while the level of ..cap alpha..-Toc increased markedly. The activities of GP/sub x/, 6-phosphogluconate dehydrogenase, SOD and disulfide reductase, and the contents of NPSH, ..cap alpha..-Toc and total lipids were also related to their LC/sub 50/. On the other hand, TBA reactants increased higher than those of the control groups and were inversely related to their LC/sub 50/. These results suggest that the protective enzymes and the antioxidants are important factors as defence mechanism in lungs to NO/sub 2/ and that the intensity of the protective systems in pigmented strains is generally greater than that in albino strains.

  20. Quantitative differences in antibiotic resistance between methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains isolated in Hungary, Austria and Macedonia.

    PubMed

    Horvath, A; Rozgonyi, F; Pesti, N; Kocsis, E; Malmos, G; Kristof, K; Nagy, K; Lagler, H; Presterl, E; Stich, K; Gattringer, R; Kotolacsi, G; Cekovska, Z; Graninger, W

    2010-08-01

    The aim of this study was to compare the quantitative susceptibility of methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA) strains from three European countries to nine antistaphylococcal agents. The antibiotic susceptibility of 274 MRSA and 284 MSSA strains from Hungary, Austria and macedonia was tested by the broth microdilution method. The clonal relationship of strains was determined by pulsed-field gel electrophoresis. Intermediate susceptibility to vancomycin appeared in Macedonian MRSA strains. Macedonian MRSA strains had high-level amikacin and gentamicin resistance. MSSA strains generally were susceptible to all drugs at minimum inhibitory concentrations (MIC(50)) except for gentamicin resistance in Macedonian strains. In Hungary and Austria a common antibiotic resistance phenotype of MRSA predominated, while in macedonia three other phenotypes were also prevalent. Geographical differences in the resistance of S. aureus are still high. Since resistance levels of MRSA and MSSA strains differ extensively, they should be considered separately for antibiotic resistance analysis.

  1. 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

  2. Genetic characteristics of one highly multi-drug-resistant strain of Klebsiella ozaenae.

    PubMed

    Huang, Jiansheng; Li, Xirong; Zhu, Naishuo; Li, Guoxiong

    2012-09-01

    One highly multi-drug-resistant, mucus-producing and foul-smelling strain of Klebsiella ozaenae was isolated from a patient in the ICU of a Chinese tertiary hospital. MICs of several clinical antimicrobials against the strain were obtained using the Vitek-2 Compact System with AST-GN13 cards and resistance genes were evaluated by PCR and gene sequencing. The strain was resistant to most of the β-lactams and quinolones tested and carried several antibiotic resistance genes, including bla(KPC-2), bla(TEM-98), bla(CTX-M-3), bla(SHV-26) and qnrS. To our knowledge, this is the first report of β-lactam and quinolone resistance genes co-existing in a K. ozaenae strain in China.

  3. Study of gene transfer in vitro and in the digestive tract of gnotobiotic mice from Lactococcus lactis strains to various strains belonging to human intestinal flora.

    PubMed

    Gruzza, M; Fons, M; Ouriet, M F; Duval-Iflah, Y; Ducluzeau, R

    1994-07-01

    The use of genetically modified organisms (GMO) in dairy products requires evaluation of the DNA transfer capacity from such organisms among the human intestinal microflora. Thus, both in vitro and in vivo [in the digestive tract (DT) of mice] transfer from Lactococcus lactis donor strains of the conjugative plasmid pIL205 (CmR) and the non-conjugative plasmid pIL253 (EmR) to: (1) recipient strains isolated from human faecal flora Bacteroides sp., Bifidobacterium sp., Peptostreptococcus sp. (strictly anaerobic bacterial strains) and Enterococcus faecalis, (2) a whole human faecal flora, was studied. In both cases, no gene transfer was observed to strictly anaerobic bacterial strains. DNA transfer was only observed to the E. faecalis strain: in vivo CmR E. faecalis transconjugants were isolated from sequentially multi-associated mice and when the recipient strains associated with the mice, they were a defined mixture of Bacteroides sp., Bifidobacterium sp., Peptostreptococcus sp. and E. faecalis strains. When mice were associated with the whole human faecal flora, the plasmid pIL205 was transferred into some facultative anaerobic streptococci. It was also shown that DNA transfer occurred even when the lactococcal donor strain was transient in the DT of the gnotobiotic host animals.

  4. 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

  5. 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.

  6. A Lactobacillus plantarum strain isolated from kefir protects against intestinal infection with Yersinia enterocolitica O9 and modulates immunity in mice.

    PubMed

    De Montijo-Prieto, Soumi; Moreno, Encarnación; Bergillos-Meca, Triana; Lasserrot, Agustín; Ruiz-López, María-Dolores; Ruiz-Bravo, Alfonso; Jiménez-Valera, María

    2015-10-01

    Lactobacillus plantarum C4, previously isolated from kefir and characterized as a potential probiotic strain, was tested for its protective and immunomodulatory capacity in a murine model of yersiniosis. The inoculation of BALB/c mice with a low pathogenicity serotype O9 strain of Yersinia enterocolitica results in a prolonged intestinal infection with colonization of Peyer's patches. Pretreatment with C4 was without effect on fecal excretion of yersiniae, but shortened the colonization of Peyer's patches. This protective effect was associated with pro-inflammatory status in the intestinal mucosa (TNF-α production in infected mice was increased by C4) and an increase in total IgA secretion. At a systemic level, C4 did not promote a pro-inflammatory response, although production of the immunoregulatory cytokine IFN-γ was enhanced. These findings suggest that L. plantarum C4 can increase resistance to intestinal infections through its immunomodulatory activity.

  7. 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

  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. 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

  10. 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.

  11. 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.

  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. Effect of Bacteriophages on the Growth of Flavobacterium psychrophilum and Development of Phage-Resistant Strains.

    PubMed

    Christiansen, Rói Hammershaimb; Madsen, Lone; Dalsgaard, Inger; Castillo, Daniel; Kalatzis, Panos G; Middelboe, Mathias

    2016-05-01

    The controlling effect of single and multiple phages on the density of Flavobacterium psychrophilum at different initial multiplicity of infection (MOI) was assessed in batch cultures to explore the potential for phage-based treatment of this important fish pathogen. A high initial phage concentration (MOI = 0.3-4) was crucial for efficient viral lysis, resulting in a 10(4)-10(5)-fold reduction of phage-sensitive cells (both single phages and phage cocktails), which was maintained throughout the incubation (>10 days). Following cell lysis, regrowth of phage-resistant strains was examined and resistant strains were isolated for further characterization. The application of a mathematical model allowed simulation of phage-host interactions and resistance development, confirming indications from strain isolations that phage-sensitive strains dominated the regrowing population (>99.8%) at low MOI and phage-resistant strains (>87.8%) dominated at high MOI. A cross-infectivity test covering 68 isolated strains and 22 phages resulted in 23 different host susceptibility patterns, with 20 of the isolates being resistant to all the applied phages. Eleven isolated strains with different susceptibility patterns had lower growth rates (0.093 to 0.31 h(-1)) than the host strain (0.33 h(-1)), while 10 of 14 examined strains had lost the ability to take up specific substrates as shown by BIOLOG profiles. Despite increased selection for phage resistance at high MOI, the results emphasize that high initial MOI is essential for fast and effective control of F. psychrophilum infection and suggest that the small populations of resistant clones had reduced competitive abilities relative to the sensitive ancestral strain.

  15. 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

  16. Diffusion and persistence of multidrug resistant Salmonella Typhimurium strains phage type DT120 in southern Italy.

    PubMed

    De Vito, Danila; Monno, Rosa; Nuccio, Federica; Legretto, Marilisa; Oliva, Marta; Coscia, Maria Franca; Dionisi, Anna Maria; Calia, Carla; Capolongo, Carmen; Pazzani, Carlo

    2015-01-01

    Sixty-two multidrug resistant Salmonella enterica serovar Typhimurium strains isolated from 255 clinical strains collected in Southern Italy in 2006-2008 were characterised for antimicrobial resistance genes, pulsotype, and phage type. Most strains (83.9%) were resistant to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline (ACSSuT) encoded in 88.5% by the Salmonella genomic island (SGI1) and in 11.5% by the InH-like integron (bla OXA-30-aadA1) and catA1, sul1, and tet(B) genes. STYMXB.0061 (75%) and DT120 (84.6%) were the prevalent pulsotype and phage type identified in these strains, respectively. Five other resistance patterns were found either in single or in a low number of isolates. The pandemic clone DT104 (ACSSuT encoded by SGI1) has been identified in Italy since 1992, while strains DT120 (ACSSuT encoded by SGI1) have never been previously reported in Italy. In Europe, clinical strains DT120 have been reported from sporadic outbreaks linked to the consumption of pork products. However, none of these strains were STYMXB.0061 and SGI1 positive. The prevalent identification and persistence of DT120 isolates would suggest, in Southern Italy, a phage type shifting of the pandemic DT104 clone pulsotype STYMXB.0061. Additionally, these findings raise epidemiological concern about the potential diffusion of these emerging multidrug resistant (SGI linked) DT120 strains.

  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. 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

  20. 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

  1. 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

  2. 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.

  3. Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice.

    PubMed

    Segall, S K; Nackley, A G; Diatchenko, L; Lariviere, W R; Lu, X; Marron, J S; Grabowski-Boase, L; Walker, J R; Slade, G; Gauthier, J; Bailey, J S; Steffy, B M; Maynard, T M; Tarantino, L M; Wiltshire, T

    2010-11-01

    Catechol-O-methyltransferase (COMT) is a ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity and risk for developing psychiatric disorders. A functional haplotype associated with increased pain sensitivity was shown to result in decreased COMT activity by altering mRNA secondary structure-dependent protein translation. However, the exact mechanisms whereby COMT modulates pain sensitivity and behavior remain unclear and can be further studied in animal models. We have assessed Comt1 gene expression levels in multiple brain regions in inbred strains of mice and have discovered that Comt1 is differentially expressed among the strains, and this differential expression is cis-regulated. A B2 short interspersed nuclear element (SINE) was inserted in the 3'-untranslated region (3'-UTR) of Comt1 in 14 strains generating a common haplotype that correlates with gene expression. Experiments using mammalian expression vectors of full-length cDNA clones with and without the SINE element show that strains with the SINE haplotype (+SINE) have greater Comt1 enzymatic activity. +SINE mice also exhibit behavioral differences in anxiety assays and decreased pain sensitivity. These results suggest that a haplotype, defined by a 3'-UTR B2 SINE element, regulates Comt1 expression and some mouse behaviors. PMID:20659173

  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.

  5. 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

  6. 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.

  7. Molecular typing of Leptospira spp. strains isolated from field mice confirms a link to human leptospirosis.

    PubMed

    Li, S J; Wang, D M; Zhang, C C; Li, X W; Yang, H M; Tian, K C; Wei, X Y; Liu, Y; Tang, G P; Jiang, X G; Yan, J

    2013-11-01

    In recent years, human leptospirosis has been reported in Jinping and Liping counties, Guizhou province, but the leptospires have never been isolated. To track the source of infection and understand the aetiological characteristics, we performed surveillance for field mice carriage of leptospirosis in 2011. Four strains of leptospire were isolated from Apodemus agrarius. PCR confirmed the four isolates as pathogenic. Multiple-locus variable-number tandem repeat analysis (MLVA) showed that the four strains were closely related to serovar Lai strain 56601 belonging to serogroup Icterohaemorrhagiae, which is consistent with the antibody detection results from local patients. Furthermore, the diversity of leptospiral isolates from different hosts and regions was demonstrated with MLVA. Our results suggest that A. agrarius may be the main carrier of Leptospira in Jinping and Liping counties, and the serogroup Icterohaemorrhagiae serovar may be the epidemic serogroup of Leptospira. This will contribute to the control and prevention of leptospirosis in these localities. PMID:23406882

  8. Effect of intestinal colonisation by two Lactobacillus strains on the immune response of gnotobiotic mice.

    PubMed

    Steinberg, R S; Lima, M; Gomes de Oliveira, N L; Miyoshi, A; Nicoli, J R; Neumann, E; Nunes, A C

    2014-12-01

    The effect of intestinal colonisation on the immune system was investigated in germ-free mice monoassociated with Lactobacillus strains isolated from calf faeces. Single doses of Lactobacillus acidophilus L36 or Lactobacillus salivarius L38 were administered to germ-free mice by intragastric gavage. Ten days later, the mice were euthanised. Gene expression levels of interleukin 5 (IL-5), IL-6, IL-10, IL-12b, IL-17a, gamma interferon (IFN-γ), transforming growth factor beta 1 (TGF-β1), and tumour necrosis factor alpha (TNF-α) were quantified in segments of the small and large intestines by real time quantitative polymerase chain reaction. All the mice were colonised rapidly after Lactobacillus administration with intestinal counts ranging from 6.53 to 8.26 log cfu/g. L. acidophilus L36 administration increased the expression of cytokines involved with the Th2 (IL-5, IL-6 and TGF-β1) and Th17 (IL-17a, TNF-α and IL-6) inflammatory response, whereas L. salivarius L38 appeared to stimulate a pattern of less diversified cytokines in the intestine. Intragastric gavage of L. acidophilus L36 and L. salivarius L38 induced similar levels of colonisation in the digestive tracts of germ-free mice but stimulated different immune responses in the intestinal mucosa. The different immunomodulation patterns might facilitate the potential use of these lactobacilli as probiotics to treat distinct pathological conditions, for example protection against Citrobacter rodentium infection by stimulating IL-17 production.

  9. 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.

  10. [Physiological properties of the vancomycin-resistant strain Staphylococcus epidermidis 33 GISK VAN(R)].

    PubMed

    Kononova, L I; Korobov, V P

    2015-01-01

    Physiological properties of a selected Staphylococcus epidermidis strain 33 GISK VAN(R) with high resistance to vancomycin, multiple resistance to various antibiotics, as well as decreased sensitivity to lysozyme, lysostaphin, and the low-molecular mass peptide warnerin were studied. The strain was characterized by a thicker cell wall, resulting in considerably decreased rates of vancomycin penetration into the cells and in limited access of the antibiotic to its targets on the bacterial membrane.

  11. Draft Genome Sequence of an Extensively Drug-Resistant Acinetobacter baumannii Indigo-Pigmented Strain.

    PubMed

    Traglia, German; Vilacoba, Elisabet; Almuzara, Marisa; Diana, Leticia; Iriarte, Andres; Centrón, Daniela; Ramírez, María Soledad

    2014-11-13

    Last year in 2013, we reported an outbreak due to indigo-pigmented Acinetobacter baumannii strains in a hospital from Buenos Aires, Argentina. Here, we present the draft genome sequence of one of the strains (A. baumannii A33405) involved in the outbreak. This isolate was categorized as extensively drug-resistant (XDR) and harbors different genetic elements associated with horizontal genetic transfer and multiple antibiotic resistances.

  12. Draft Genome Sequence of an Extensively Drug-Resistant Acinetobacter baumannii Indigo-Pigmented Strain

    PubMed Central

    Traglia, German; Vilacoba, Elisabet; Almuzara, Marisa; Diana, Leticia; Iriarte, Andres; Centrón, Daniela

    2014-01-01

    Last year in 2013, we reported an outbreak due to indigo-pigmented Acinetobacter baumannii strains in a hospital from Buenos Aires, Argentina. Here, we present the draft genome sequence of one of the strains (A. baumannii A33405) involved in the outbreak. This isolate was categorized as extensively drug-resistant (XDR) and harbors different genetic elements associated with horizontal genetic transfer and multiple antibiotic resistances. PMID:25395633

  13. Detection of a second mechanism of resistance to gentamicin in animal strains of Escherichia coli.

    PubMed Central

    Chaslus-Dancla, E; Gerbaud, G; Martel, J L; Lagorce, M; Lafont, J P; Courvalin, P

    1987-01-01

    One mechanism of plasmid-mediated resistance to gentamicin in Escherichia coli strains isolated from animals is due to the synthesis of the aminoglycoside 3-N-acetyltransferase type IV. A second mechanism of plasmid-mediated resistance to gentamicin was detected in animal strains of E. coli in France and is due to the production of the aminoglycoside 3-N-acetyltransferase type II. The molecular relationships among plasmids encoding this enzyme were studied. Images PMID:3307622

  14. [Physiological properties of the vancomycin-resistant strain Staphylococcus epidermidis 33 GISK VAN(R)].

    PubMed

    Kononova, L I; Korobov, V P

    2015-01-01

    Physiological properties of a selected Staphylococcus epidermidis strain 33 GISK VAN(R) with high resistance to vancomycin, multiple resistance to various antibiotics, as well as decreased sensitivity to lysozyme, lysostaphin, and the low-molecular mass peptide warnerin were studied. The strain was characterized by a thicker cell wall, resulting in considerably decreased rates of vancomycin penetration into the cells and in limited access of the antibiotic to its targets on the bacterial membrane. PMID:25916148

  15. Genetic Characterization of Fluoroquinolone-Resistant Streptococcus pneumoniae Strains Isolated during Ciprofloxacin Therapy from a Patient with Bronchiectasis

    PubMed Central

    de la Campa, Adela G.; Ferrandiz, María-José; Tubau, Fe; Pallarés, Román; Manresa, Federico; Liñares, Josefina

    2003-01-01

    Five Spain9V-3 Streptococcus pneumoniae strains were isolated from a patient with bronchiectasis who had received long-term ciprofloxacin therapy. One ciprofloxacin-susceptible strain was isolated before treatment, and four ciprofloxacin-resistant strains were isolated during treatment. The resistant strains were derived from the susceptible strain either by a parC mutation (low-level resistance) or by parC and gyrA mutations (high-level resistance). This study shows that ciprofloxacin therapy in a patient colonized by susceptible S. pneumoniae may select fluoroquinolone-resistant mutants. PMID:12654682

  16. Development and characterization of PdCr temperature-compensated wire resistance strain gage

    NASA Technical Reports Server (NTRS)

    Lei, Jih-Fen

    1989-01-01

    A temperature-compensated resistance static strain gage with potential to be used to 600 C was recently developed. Gages were fabricated from specially developed palladium-13 w/o chromium (Pd-13Cr) wire and platinum (Pt) compensator. When bonded to high temperature Hastelloy X, the apparent strain from room temperature to 600 C was within 400 microstrain for gages with no preheat treatment and within 3500 microstrain for gages with 16 hours prestabilization at 640 C. The apparent strain versus temperature relationship of stabilized PdCr gages were repeatable with the reproducibility within 100 microstrain during three thermal cycles to 600 C and an 11 hours soak at 600 C. The gage fabrication, construction and installation is described. Also, the coating system used for this compensated resistance strain gage is explained. The electrical properties of the strain sensing element and main characteristics of the compensated gage including apparent strain, drift and reproducibility are discussed.

  17. Development and characterization of PdCr temperature-compensated wire resistance strain gage

    NASA Astrophysics Data System (ADS)

    Lei, Jih-Fen

    1989-10-01

    A temperature-compensated resistance static strain gage with potential to be used to 600 C was recently developed. Gages were fabricated from specially developed palladium-13 w/o chromium (Pd-13Cr) wire and platinum (Pt) compensator. When bonded to high temperature Hastelloy X, the apparent strain from room temperature to 600 C was within 400 microstrain for gages with no preheat treatment and within 3500 microstrain for gages with 16 hours prestabilization at 640 C. The apparent strain versus temperature relationship of stabilized PdCr gages were repeatable with the reproducibility within 100 microstrain during three thermal cycles to 600 C and an 11 hours soak at 600 C. The gage fabrication, construction and installation is described. Also, the coating system used for this compensated resistance strain gage is explained. The electrical properties of the strain sensing element and main characteristics of the compensated gage including apparent strain, drift and reproducibility are discussed.

  18. [Antimicrobial resistance and molecular epidemiology of Staphylococcus pseudintermedius strains isolated from dog clinical samples].

    PubMed

    Vigo, Germán B; Giacoboni, Gabriela I; Gagetti, Paula S; Pasterán, Fernando G; Corso, Alejandra C

    2015-01-01

    Twenty-eight strains isolated from dog clinical samples identified as Staphylococcus pseudintermedius by mass spectrometry (MALDI-TOF) were studied to assess antimicrobial susceptibility by the diffusion method and clonal relationship by pulsed field gel electrophoresis (PFGE). Methicillin resistance (3/28 isolates; 10,7%) was evaluated by mecA PCR. Fifteen strains (53.6%) were resistant to at least one of the antibiotics tested, and eleven of them (39.3%) showed multiple resistance (3 or more antimicrobial families). Eleven isolates (39.3%) were resistant to erythromycin due to the presence of ribosomal methylase ermB, whereas clindamycin inducible resistance was not detected. Twenty-seven (27) clonal types were differentiated by PFGE, suggesting high clonal diversity. We emphasize that the finding of multiresistant S. psedintermedius strains is an emerging problem to be considered in veterinary diagnostic laboratory treatment of canine infections and in public health settings.

  19. Pyrethroid insecticide-resistant strain of Aedes aegypti from Cuba induced by deltamethrin selection.

    PubMed

    Rodríguez, María M; Bisset, Juan A; De Armas, Yaxsier; Ramos, Francisco

    2005-12-01

    A sample of Aedes aegypti L. from Santiago de Cuba with a high level of deltamethrin resistance (113.7 x at the 50% lethal concentration [LC50]), was subjected to deltamethrin selection to determine the capacity of this population to evolve higher resistance under intensive laboratory selection pressure, to characterize that resistance, to attempt to identify some of the mechanisms involved, and to use it as a reference strain for future molecular research. High resistance developed after 12 generations of selection (1,425 x). After selection for 12 generations with deltamethrin, the Santiago de Cuba colony (SAN-F12) showed little or no cross-resistance to the organophosphates evaluated, but high cross-resistance was observed for all the pyrethroids in larvae from this strain: lambdacyhalothrin (197.5 x), cypermethrin (45 x), and cyfluthrin (41.2 x). Adult bioassays reveal that a SAN-F12 strain was resistant to the pyrethroid and the organochlorine dichlorodiphenyltrichloroethane (DDT). Synergism tests implicated detoxifying esterase or glutathione S-transferase (GST) and monooxygenase in pyrethroid resistance. Biochemical tests reveal that acetylcholinesterase was not involved in deltamethrin resistance. The frequency of GST enzyme increased from 0.43 in Santiago de Cuba to 0.88 in SAN-F12. Esterase frequency increased from 0.12 in Santiago de Cuba to 0.63 in SAN-F6 and it diminished to 0.38 in SAN-F12. The polyacrylamide gel electrophoresis and inhibition study suggests the presence of elevated esterase activity not associated with pyrethroid resistance. The presence of both DDT and pyrethroid resistance in the SAN-F12 strain suggests the presence of a knockdown (Kdr)-type resistance mechanism, although the frequency of this mechanism was low. Resistance to deltamethrin could be associated with esterase or GST mechanisms, and more investigation is required. This information contributes to the improvement of resistance management strategies in the Cuban Ae

  20. 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

  1. Antimicrobial resistance and production of biofilms in clinical isolates of coagulase-negative Staphylococcus strains.

    PubMed

    de Allori, María Cristina Gaudioso; Jure, María Angela; Romero, Cintia; de Castillo, Marta Elena Cecilia

    2006-08-01

    Coagulase-negative Staphylococcus (CNS) strains are frequently associated with bacteremia and hospital-acquired infections. 293 CNS strains were isolated from 744 samples from a dialysis center in S. M. de Tucumán, Argentina, from hemocultures, catheters and urine and identified as S. epidermidis, S. haemolyticus, S. saprophyticus, S. hominis and S. cohnii. 13 antibiotics were tested for antibacterial resistance. 75% of S. saprophyticus, 66% of S. epidermidis and 57% of S. haemolyticus was resistant to erythromycin and 50% of S. haemolyticus was resistant to ciprofloxacin. OXA resistance was found in 43% of S. haemolyticus. Presence of PBP 2a in OXA-R strains was confirmed with the modified agglutination assay (MRSA) and presence of the mecA gene. 15 strains with intermediate halos for vancomycin and teicoplanin showed a MIC in solid and liquid medium strains produced biofilms: 42% of S. haemolyticus and 40% of S. epidermidis. 76% of the S. epidermidis and 59% of the S. haemolyticus biofilm-producing strains were isolated from catheters. The disc-diffusion technique together with the agglutination assay proved to be fast and reliable, which is of essential importance in intensive care units. Rapid identification of CNS strains, detection of resistance to methicillin and biofilm production are decisive for a prompt and appropriate antimicrobial therapy and limited use of inappropriate glycopeptides.

  2. A resistance strain gage with repeatable and cancellable apparent strain for use to 800 C

    NASA Astrophysics Data System (ADS)

    Lei, Jih-Fen

    1990-07-01

    A temperature compensated static strain gage, which is fabricated from palladium-13w/o chromium (Pd13Cr) alloy and a platinum (Pt) compensator, is being developed and was tested over a temperature range to 800 C at NASA-Lewis. The PdCr compensated strain gage has significantly lower apparent strain to 800 C than other high temperature strain gages. The PdCr compensated gage is protected from oxidation by a flame-sprayed alumina-4w/o zirconia overcoating. Test results to 800 C indicate apparent strain variations of less than 300 micro-epsilon and reproducibility between thermal cycles within 50 micro-epsilon. Apparent strain of the coated PdCr compensated gage can be predicted and cancelled due to its reproducibility and low value.

  3. A resistance strain gage with repeatable and cancellable apparent strain for use to 800 C

    NASA Technical Reports Server (NTRS)

    Lei, Jih-Fen

    1990-01-01

    A temperature compensated static strain gage, which is fabricated from palladium-13w/o chromium (Pd13Cr) alloy and a platinum (Pt) compensator, is being developed and was tested over a temperature range to 800 C at NASA-Lewis. The PdCr compensated strain gage has significantly lower apparent strain to 800 C than other high temperature strain gages. The PdCr compensated gage is protected from oxidation by a flame-sprayed alumina-4w/o zirconia overcoating. Test results to 800 C indicate apparent strain variations of less than 300 micro-epsilon and reproducibility between thermal cycles within 50 micro-epsilon. Apparent strain of the coated PdCr compensated gage can be predicted and cancelled due to its reproducibility and low value.

  4. A resistance strain gage with repeatable and cancellable apparent strain for use to 1500 F

    NASA Astrophysics Data System (ADS)

    Lei, Jih-Fen

    A temperature compensated static strain gauge, which is fabricated from Pd13Cr alloy and a Pt compensator, is being developed and has been tested over a temperature range to 1500 F at NASA-Lewis. The PdCr compensated strain gage has significantly lower apparent strain to 500 F than other high temperature strain gages. The PdCr compensated gage is protected from oxidation by a flame-sprayed alumina-4 wt pct zirconia overcoating. Test Results to 1500 F indicate apparent strain variations of less than 250 micro-epsilon and reproducibility between thermal cycles within 50 micro-epsilon. The apparent strain of the coated PdCr compensated gage can be predicted and cancelled due to its reproducibility and low value.

  5. Transduction of Methicillin Resistance in Staphylococcus aureus Dependent on an Unusual Specificity of the Recipient Strain

    PubMed Central

    Cohen, Sidney; Sweeney, Helen M.

    1970-01-01

    Resistance to methicillin was transduced by phage 80 or 53 from two naturally occurring methicillin-resistant strains of Staphylococcus aureus to methicillin-susceptible recipient strains at frequencies of 10−7 to 10−9. Ultraviolet irradiation of transducing phage and posttransductional incubation at 30 C were essential for useful frequencies of transduction. Effectiveness as a recipient for this transduction was highly specific. Strain NCTC 8325 (PS47) in its native state was an ineffective recipient but became effective after it had received by transduction one of several penicillinase plasmids. This acquired effectiveness was retained in most cases after elimination of the plasmid by ethidium bromide treatment. Like the donor strain, the progeny were heterogeneous in the degree of their resistance to methicillin, which was expressed by a higher proportion of cells as the temperature of incubation was lowered from 37 to 30 C. Separate transductants varied widely in the degree of resistance acquired by transduction. Methicillin resistance was stable in the donor and transductant strains. We favored the interpretation that methicillin resistance in our strains was determined by a single chromosomal gene, although the possibility that it was determined by two or more closely linked genes could not be excluded. PMID:16559089

  6. Resistance to acetaminophen-induced hepatotoxicity in glutathione S-transferase Mu 1-null mice.

    PubMed

    Arakawa, Shingo; Maejima, Takanori; Fujimoto, Kazunori; Yamaguchi, Takashi; Yagi, Masae; Sugiura, Tomomi; Atsumi, Ryo; Yamazoe, Yasushi

    2012-01-01

    We investigated the role of glutathione S-transferases Mu 1 (GSTM1) in acetaminophen (APAP)-induced hepatotoxicity using Gstm1-null mice. A single oral administration of APAP resulted in a marked increase in plasma alanine aminotransferase accompanied by hepatocyte necrosis 24 hr after administration in wild-type mice, but its magnitude was unexpectedly attenuated in Gstm1-null mice. Therefore, it is suggested that Gstm1-null mice are resistant to APAP-induced hepatotoxicity. To examine the mechanism of this resistance in Gstm1-null mice, we measured phosphorylation of c-jun N-terminal kinase (JNK), which mediates the signal of APAP-induced hepatocyte necrosis, by Western blot analysis 2 and 6 hr after APAP administration. A marked increase in phosphorylated JNK was observed in wild-type mice, but the increase was markedly suppressed in Gstm1-null mice. Therefore, it is suggested that suppressed phosphorylation of JNK may be a main mechanism of the resistance to APAP-induced hepatotoxicity in Gstm1-null mice, although other possibilities of the mechanism cannot be eliminated. Additionally, phosphorylation of glycogen synthase kinase-3β and mitogen-activated protein kinase kinase 4, which are upstream kinases of JNK in APAP-induced hepatotoxicity, were also suppressed in Gstm1-null mice. A decrease in liver total glutathione 2 hr after APAP administration, which is an indicator for exposure to N-acetyl-p-benzoquinoneimine, the reactive metabolite of APAP, were similar in wild-type and Gstm1-null mice. In conclusion, Gstm1-null mice are considered to be resistant to APAP-induced hepatotoxicity perhaps by the suppression of JNK phosphorylation. This study indicates the novel role of GSTM1 as a factor mediating the cellular signal for APAP-induced hepatotoxicity.

  7. Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in the BXD2 recombinant inbred strain of mice.

    PubMed

    Mountz, J D; Yang, P; Wu, Q; Zhou, J; Tousson, A; Fitzgerald, A; Allen, J; Wang, X; Cartner, S; Grizzle, W E; Yi, N; Lu, L; Williams, R W; Hsu, H-C

    2005-02-01

    The BXD2 strain of mice is one of approximately 80 BXD recombinant inbred (RI) mouse strains derived from an intercross between C57BL/6J (B6) and DBA/2J (D2) strains. We have discovered that adult BXD2 mice spontaneously develop generalized autoimmune disease, including glomerulonephritis (GN), increased serum titres of rheumatoid factor (RF) and anti-DNA antibody, and a spontaneous erosive arthritis characterized by mononuclear cell infiltration, synovial hyperplasia, and bone and cartilage erosion. The features of lupus and arthritis developed by the BXD2 mice segregate in F2 mice generated by crossing BXD2 mice with the parental B6 and D2 strains. Genetic linkage analysis of the serum levels of anti-DNA and RF by using the BXD RI strains shows that the serum titers of anti-DNA and RF were influenced by a genetic locus on mouse chromosome (Chr) 2 near the marker D2Mit412 (78 cm, 163 Mb) and on Chr 4 near D4Mit146 (53.6 cm, 109 Mb), respectively. Both loci are close to the B-cell hyperactivity, lupus or GN susceptibility loci that have been identified previously. The results of our study suggest that the BXD2 strain of mice is a novel model for complex autoimmune disease that will be useful in identifying the mechanisms critical for the immunopathogenesis and genetic segregation of lupus and erosive arthritis.

  8. 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.

  9. 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

  10. Toxoplasma gondii Oral Infection Induces Intestinal Inflammation and Retinochoroiditis in Mice Genetically Selected for Immune Oral Tolerance Resistance

    PubMed Central

    Dias, Raul Ramos Furtado; de Carvalho, Eulógio Carlos Queiroz; Leite, Carla Cristina da Silva; Tedesco, Roberto Carlos; Calabrese, Katia da Silva; Silva, Antonio Carlos; DaMatta, Renato Augusto; de Fatima Sarro-Silva, Maria

    2014-01-01

    Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis. PMID:25437299

  11. A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice.

    PubMed

    Rodriguez, Marisela R; Lundgren, Alyssa; Sabastian, Pearl; Li, Qian; Churchill, Gary; Brown, Michael G

    2009-07-01

    NK cell-mediated resistance to viruses is subject to genetic control in humans and mice. Here we used classical and quantitative genetic strategies to examine NK-mediated murine cytomegalovirus (MCMV) control in genealogically related New Zealand white (NZW) and black (NZB) mice. NZW mice display NK cell-dependent MCMV resistance while NZB NK cells fail to limit viral replication after infection. Unlike Ly49H(+) NK resistance in C57BL/6 mice, NZW NK-mediated MCMV control was Ly49H-independent. Instead, MCMV resistance in NZW (Cmv2) involves multiple genetic factors. To establish the genetic basis of Cmv2 resistance, we further characterized a major chromosome X-linked resistance locus (DXMit216) responsible for innate MCMV control in NZW x NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F(2) crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F(2) males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains.

    PubMed

    Raymond, Gregory J; Raymond, Lynne D; Meade-White, Kimberly D; Hughson, Andrew G; Favara, Cynthia; Gardner, Donald; Williams, Elizabeth S; Miller, Michael W; Race, Richard E; Caughey, Byron

    2007-04-01

    In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

  19. The Chemokine CXCL12 Is Essential for the Clearance of the Filaria Litomosoides sigmodontis in Resistant Mice

    PubMed Central

    Attout, Tarik; Ehrhardt, Katharina; Lhermitte-Vallarino, Nathaly; Hachet-Haas, Muriel; Galzi, Jean Luc; Brotin, Emilie; Bachelerie, Françoise; Gavotte, Laurent; Moulia, Catherine; Bain, Odile; Martin, Coralie

    2012-01-01

    Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms. PMID:22511975

  20. Over-expression of homologous antigens in a leucine auxotroph of Brucella abortus strain RB51 protects mice against a virulent B. suis challenge.

    PubMed

    Rajasekaran, Parthiban; Surendran, Naveen; Seleem, Mohamed N; Sriranganathan, Nammalwar; Schurig, Gerhardt G; Boyle, Stephen M

    2011-04-12

    Infection by members of the Gram-negative bacterial genus Brucella causes brucellosis in a variety of mammals. Brucellosis in swine remains a challenge, as there is no vaccine in the USA approved for use in swine against brucellosis. Here, we developed an improved recombinant Brucella abortus vaccine strain RB51 that could afford protection against Brucella suis infection by over-expressing genes encoding homologous proteins: L7/L12 ribosomal protein, Cu/Zn superoxide dismutase [SOD] and glycosyl-transferase [WboA]. Using strain RB51leuB as a platform and an antibiotic-resistance marker free plasmid, strains RB51leuB/SOD, RB51leuB/SOD/L7/L12 and RB51leuB/SOD/WboA were constructed to over-express the antigens: SOD alone, SOD and ribosomal protein L7/L12 or SOD and glycosyl-transferase, respectively. The ability of these vaccine candidates to protect against a virulent B. suis challenge were evaluated in a mouse model. All vaccine groups protected mice significantly (P<0.05) when compared to the control group. Within the vaccine groups, the mice vaccinated with strain RB51leuB/SOD/WboA were significantly better protected than those that were vaccinated with either strain RB51leuB/SOD or RB51leuB/SOD/L7/L12. These results suggest that Brucella antigens can be over-expressed in strain RB51leuB and elicit protective immune responses against brucellosis. Since the plasmid over-expressing homologous antigens does not carry an antibiotic resistance gene, it complies with federal regulations and therefore could be used to develop safer multi-species vaccines for prevention of brucellosis caused by other species of Brucella.

  1. 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

  2. Pre-multidrug-resistant Mycobacterium tuberculosis Beijing strain associated with disseminated tuberculosis in a pet dog.

    PubMed

    Botelho, Ana; Perdigão, João; Canto, Ana; Albuquerque, Teresa; Leal, Nuno; Macedo, Rita; Portugal, Isabel; Cunha, Mónica V

    2014-01-01

    Resistance to isoniazid, ethambutol, and streptomycin was detected in a Mycobacterium tuberculosis strain, belonging to the Beijing family lineage, isolated from two nodule exudates of a Yorkshire terrier with generalized tuberculosis. This report alerts medical practitioners to the risk of dissemination of pre-multidrug-resistant tuberculosis (preMDR-TB) through exposure to M. tuberculosis-shedding pets.

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

    PubMed

    Zhang, Rong; Lin, Dachuan; Chan, Edward Wai-Chi; Gu, Danxia; Chen, Gong-Xiang; Chen, Sheng

    2016-01-01

    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 bla(KPC-2) gene. These findings indicate that K1 hvKP is simultaneously hypervirulent, multidrug resistant, and transmissible. PMID:26574010

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

    PubMed

    Zhang, Rong; Lin, Dachuan; Chan, Edward Wai-Chi; Gu, Danxia; Chen, Gong-Xiang; Chen, Sheng

    2015-11-16

    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 bla(KPC-2) gene. These findings indicate that K1 hvKP is simultaneously hypervirulent, multidrug resistant, and transmissible.

  5. Identification of a Lactobacillus plantarum strain that ameliorates chronic inflammation and metabolic disorders in obese and type 2 diabetic mice.

    PubMed

    Toshimitsu, T; Mochizuki, J; Ikegami, S; Itou, H

    2016-02-01

    In this study, we identified a strain of lactic acid bacteria (LAB) that induces high levels of IL-10 production by immune cells, and evaluated the ability of the strain to suppress chronic inflammation and ameliorate metabolic disorders in in vitro and in vivo models. Among a collection of LAB strains, Lactobacillus plantarum strain OLL2712 (OLL2712) induced the highest levels of IL-10 production in mouse-derived dendritic cells and peritoneal macrophages. The anti-inflammatory effects of this strain were evaluated using a co-culture system comprising RAW 264.7 and 3T3-L1 cells. We also administered heat-killed OLL2712 to obese and type 2 diabetic KKAy mice for 3 wk to evaluate the in vivo effects of the strain. The OLL2712 significantly decreased the production of proinflammatory cytokines in vitro. Likewise, the administration of OLL2712 significantly suppressed proinflammatory cytokine levels in both the visceral adipose tissue and the serum of KKAy mice, and reduced serum triglyceride concentrations. The strain also alleviated oxidative stress and adrenaline levels in the serum of KKAy mice. On the other hand, Lactobacillus gasseri strain MEP222804 (a moderate IL-10 inducer) did not ameliorate the systemic inflammation and hyperlipidemia in KKAy mice. Our results suggest that treatment with strong IL-10-inducing LAB has the potential to ameliorate metabolic disorders by suppressing chronic inflammation in the host animal.

  6. 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.

  7. Serum resistance, gallium nitrate tolerance and extrapulmonary dissemination are linked to heme consumption in a bacteremic strain of Acinetobacter baumannii.

    PubMed

    de Léséleuc, Louis; Harris, Greg; KuoLee, Rhonda; Xu, H Howard; Chen, Wangxue

    2014-05-01

    Bacteremia caused by Acinetobacter baumannii is a highly lethal complication of hospital-acquired pneumonia. In the present study, we investigated the serum resistance, gallium nitrate tolerance and heme consumption of A. baumannii strain LAC-4 which was recently reported to display high virulence in a mouse pneumonia model with extrapulmonary dissemination leading to fatal bacteremia. This strain showed enhanced growth in mouse and fetal bovine serum that was independent of complement and was not observed with regular growth media. The LAC-4 strain was found to possess a high tolerance to gallium nitrate (GaN), whereas serum synergized with GaN in inhibiting A. baumannii strain ATCC 17978. We found that LAC-4 contains a heme oxygenase gene and expresses a highly efficient heme consumption system. This system can be fully blocked in vitro and in vivo by gallium protoporphyrin IX (GaPPIX). Inhibition of heme consumption by GaPPIX completely abrogated the growth advantage of LAC-4 in serum as well as its tolerance to GaN. More importantly, GaPPIX treatment of mice intranasally infected with LAC-4 prevented extrapulmonary dissemination and death. Thus, we propose that heme provides an additional source of iron for LAC-4 to bypass iron restriction caused by serum transferrin, lactoferrin or free gallium salts. Heme consumption systems in A. baumannii may constitute major virulence factors for lethal bacteremic isolates.

  8. Depressive-like immobility behavior and genotype × stress interactions in male mice of selected strains.

    PubMed

    Chmielarz, Piotr; Kreiner, Grzegorz; Kuśmierczyk, Justyna; Kowalska, Marta; Roman, Adam; Tota, Katarzyna; Nalepa, Irena

    2016-01-01

    In this study, we investigated whether basal immobility time of C57BL/6J mice, which are commonly used in transgenesis, interferes with detection of depressive-like behavior in the tail suspension test (TST) after chronic restraint stress (CRS). We included in the study mice of the C57BL/6N strain, not previously compared with C57BL/6J for behavior in the TST, and contrasted both strains with NMRI mice which exhibit low basal immobility. NMRI, C57BL/6J, and C57BL/6N male mice (n = 20 per strain) were tested under basal conditions and after CRS (2 h daily for 14 d). NMRI and C57BL/6J mice were differentiated in the TST by low and high basal immobility times, respectively, while the C57BL/6N and NMRI mice showed similar levels of basal immobility. CRS extended the immobility time of NMRI mice in the TST, whereas both C57BL/6J and C57BL/6N mice were unaffected regardless of their initial phenotype. We explored whether detailed analysis of activity microstructure revealed effects of CRS in the TST, which are not apparent in the overall comparison of total immobility time. Interestingly, unlike C57BL/6J and/6N strains which showed no sensitivity to CRS, stressed NRMI mice displayed distinct activity microstructure. In contrast to behavioral differences, all stressed mice showed significant retardation in body weight gain, decreased thymus weight and increased adrenal cortex size. However, after CRS, enlargement of the adrenal medulla was observed in both C57BL/6J and C57BL/6N mice, suggesting similar sympatho-medullary activation and stress coping mechanism in these substrains.

  9. LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome

    PubMed Central

    Pinheiro, Iris; Dejager, Lien; Petta, Ioanna; Vandevyver, Sofie; Puimège, Leen; Mahieu, Tina; Ballegeer, Marlies; Van Hauwermeiren, Filip; Riccardi, Carlo; Vuylsteke, Marnik; Libert, Claude

    2013-01-01

    Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to depend on the glucocorticoid receptor (GR), maps to the distal region of the X-chromosome. The GR-inducible gene Tsc22d3, encoding the protein Gilz and located in the critical region on the X-chromosome, showed a higher expressed SPRET/Ei allele, regulated in cis. Higher Gilz levels were causally related to reduced inflammation, as shown with knockdown and overexpression studies in macrophages. Transient overexpression of Gilz by hydrodynamic plasmid injection confirmed that Gilz protects mice against endotoxemia Our data strongly suggest that Gilz is responsible for the LPS resistance of SPRET/Ei mice and that it could become a treatment option for sepsis. PMID:23495141

  10. Human influenza A viruses isolated in South America: genetic relations, adamantane resistance and vaccine strain match.

    PubMed

    Goñi, Natalia; Russi, José; Cristina, Juan

    2009-03-01

    In order to gain insight into the genetic relations among H3N2 Influenza A virus (IAV) circulating in the South American region from 1999 to 2007, to investigate the presence of adamantane-resistant strains in this region, and to establish the genetic relations among that strains and vaccine strains recommended for the Southern hemisphere, 11 haemagglutinin (HA) H3 IAV sequences obtained from Uruguayan patients were aligned with corresponding sequences from 68 H3 IAV strains isolated in South America and 9 H3 IAV vaccine strains. Maximum likelihood phylogenetic tree analysis was performed using the GTR evolutionary model. The results of these studies indicate that multiple clades co-circulate during most influenza seasons in South America. Strikingly, one strain isolated in Uruguay in 2005 and all strains isolated in that country during the 2007 season bear an HA adamantane-resistant polymorphism. No other strain isolated in South America previous to the 2005 season bears that HA characteristic amino acid change. Only vaccine strains recommended for the 2007 season were assigned to the same cluster with all available IAV isolated in South America for that season. Evolution of IAV in this region appears to be shaped by re-introduction of new strains.

  11. [PCR-RAPD typing of carbapenem-resistant Pseudomonas aeruginosa strains].

    PubMed

    Bogiel, Tomasz; Gospodarek, Eugenia

    2010-01-01

    P. aeruginosa rods are opportunistic pathogens responsible generally for nosocomial infections. Resistance to carbapenems, observed among them, is a serious threat due to ability to be transmitted between bacterial species. The aim of our study was to evaluate the usefulness of PCR-RAPD technique in typing of 16 carbapenem-resistant P. aeruginosa strains isolated in 2007 from different patients of University HospitalNo. 1 of dr A. Jurasz Collegium Medicum of L. Rydygier in Bydgoszcz Nicolaus Copernicus University in Toruń. Study shows increasing frequency of isolation that type of strains when compared to 2006. Percentage of carbapenem-resistant isolates raised from 12,4% in 2006 to 22.9% in 2007. The majority of examined strains were obtained from patients of the Intensive Care Units (25.0%) and were isolated from bronchoalveolar lavage (25.0%), urine (25.0%) and wound swabs (18.8%) samples. Examined P. aeruginosa strains demonstrated resistance to doripenem (81.3%) and piperacillin (75.0%) and susceptibility to colistin (100.0%), amikacin (81.3%), netilmicin and norfloxacin (75.0% each). Using PCR-RAPD amplification with 208 and 272 primers, 14 and 16 DNA patterns were obtained, respectively. Usefulness of PCR-RAPD in carbapenem-resistant P. aeruginosa strains typing was proved in case of strains presenting similar and/or different antimicrobials susceptibility patterns.

  12. Antimicrobial Resistance and Plasmid Profile of Bacterial Strains Isolated from the Urbanized Eltsovka-1 River (Russia).

    PubMed

    Lobova, Tatiana I; Yemelyanova, Elena; Andreeva, Irina S; Puchkova, Larisa I; Repin, Vladimir Ye

    2015-08-01

    Antimicrobial resistance and plasmid profile of Gram-positive and Gram-negative bacterial strains isolated from the urbanized Eltsovka-1 River (Russia) were investigated. Sequencing of the 16S rRNA of of G+ strains showed 99-100% identity to that of Bacillus aerophilus, Bacillus altitudinis, Bacillus amyloliquefaciens, Bacillus anthrancis, Bacillus barbaricus, Bacillus cereus, Bacillus flexus, Bacillus indriensis, Bacillus stratosphericus, Bacillus subtilis subsp. subtilis, Bacillus thuringiensis, Streptomyces albidoflavus, Streptomyces albus, Streptomyces exfoliatus, Streptomyces odorifer, and Streptomyces sampsonii. Sequencing of the 16S rRNA of G-strains was similar in 99-100% to that of Aeromonas bestiarum, Aeromonas encheleia, Aeromonas hydrophila, A. hydrophila subsp. anaerogenes, A. hydrophila subsp. dhakensis, Aeromonas media, Aeromonas molluscorum, Aeromonas popoffii, Aeromonas salmonicida subsp. masoucida, A. salmonicida subsp. pectinolytica, A. salmonicida subsp. salmonicida, Aeromonas punctata, Aeromonas sobria, and Shewanella putrefaciens. The highest percentage (88.4%) of strains was resistant to polymyxin B followed by 69% to lincomycin, 61.5% to benzilpenicillin, 57.7% to ampicillin, and 50% to carbenicillin. A low level of resistance (4%) was found to kanamycin (8%), to streptomycin (11.5%), to neomycin and tetracycline, and (15%) to erythromycin. No resistance was found to gentamycin, monomycin, and chloroamphenicol. The majority (80.7%) of strains was multidrug-resistant. Ninety-two percent of all strains carried plasmid DNA of various sizes.

  13. [High level of aminoglycoside resistance among Enterococcus faecalis and Enterococcus faecium strains].

    PubMed

    Kozuszko, Sylwia; Białucha, Agata; Bogiel, Tomasz; Gospodarek, Eugenia

    2011-01-01

    Enterococcus sp. strains are believed as important reason of serious nosocomial infections currently. These infections are cured by using combination of beta-lactams and aminoglycosides for their treatment. Enterococcus sp. resistant to high-level doses of aminoglycosides, beta-lactams and vancomycin are responsible for therapeutic failure. The aim of our study was to evaluate the incidence of isolation and susceptibility to antibiotics of HLAR Enterococcus sp. strains isolated between 2007 and 2010 from the patients of University Hospital No. 1 of dr A. Jurasz Collegium Medicum of L. Rydygier in Bydgoszcz Nicolaus Copernicus University in Toruń. Amongst 6137 Enterococcus sp. strains 1124 (18,3%) presented HLAR phenotype; 53,1% of them was identified as E. faecalis and 46,9% as E. faecium. The highest percentage of all examined strains was isolated from the patients of different surgery clinics, Intensive Care Units, and Pediatrics, Hematology and Oncology Clinic. HLAR and HLSR phenotypes were noted in E. faecalis, for 45,7% and 27,5% strains, in E. faecium - 29,8% and 9,5%, respectively. HLGR phenotype was presented twice more often in E. faecium than E. faecalis. Highest percentages of E. faecium resistant to glycopeptides and rifampicin were observed when compared with E. faecalis. The highest percentages of strains intermediate, resistant to vancomycin and resistant to glycopeptides were noted for E. faecium strains with phenotypes HLAR, HLGR and HLSR.

  14. 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.

  15. 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

  16. Development of ceftriaxone resistance affects the virulence properties of Salmonella enterica serotype Typhimurium strains.

    PubMed

    Li, Liang; Yang, Yu-Rong; Liao, Xiao-Ping; Lei, Chun-Yin; Sun, Jian; Li, Lu-Lu; Liu, Bao-Tao; Yang, Shou-Shen; Liu, Ya-Hong

    2013-01-01

    Development of antibiotic resistance may alter the virulence properties of bacterial organisms. In this study, nine clinical ceftriaxone-susceptible Salmonella enterica serotype Typhimurium strains were subjected to stepwise selection with increasing concentrations of ceftriaxone in culture media. Mutations in virulence-associated genes and antibiotic efflux genes were analyzed by polymerase chain reaction (PCR) and DNA sequencing. The expression levels of virulence genes invA and stn as well as efflux pump genes tolC, arcA, and arcB before and after the selection were measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The stepwise selection resulted in the development of Salmonella strains that were highly resistant to ceftriaxone. Sequence analysis did not reveal any mutations or deletions in the examined virulence genes and regulatory gene, but a silent mutation (T423C) in acrR (encoding a repressor for the efflux pump) was detected in most of the ceftriaxone-resistant strains. The qRT-PCR revealed increased expression of the AcrAB-TolC efflux pump and decreased expression of invA and stn in the ceftriaxone-resistant strains. Moreover, decreased invasion into cultured epithelial cells and reduced growth rates were observed with the resistant strains. These results suggest that acquisition of ceftriaxone resistance is associated with the overexpression of the AcrAB-TolC efflux pump and leads to reduced virulence in Salmonella Typhimurium.

  17. 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

  18. Enhancement of Natural Resistance to Influenza Virus in Lipopolysaccharide-Responsive and -Nonresponsive Mice by Propionibacterium acnes

    PubMed Central

    Gangemi, J. David; Hightower, James A.; Jackson, Ronnie A.; Maher, Michael H.; Welsh, Marcia G.; Sigel, M. Michael

    1983-01-01

    Lipopolysaccharide-responsive C3H/HeN mice were rendered resistant to a mouse-adapted strain of influenza (Aichi, H3N2) virus when Propionibacterium acnes was given either intranasally or intraperitoneally several days before virus infection. The time of P. acnes treatment was important since no protection was demonstrated when this agent was given either on the same day as or several days after virus challenge. In contrast, lipopolysaccharide-nonresponsive C3H/HeJ mice were not protected when P. acnes was administered intranasally at any time before infection; however, protection was demonstrated when P. acnes was given by the intraperitoneal route. Depending on the route of inoculation, P. acnes induced several distinctive immunological responses in the lungs of both C3H/HeN and C3H/HeJ mice. Intranasal inoculation was more effective in activating pulmonary macrophages in C3H/HeN than in C3H/HeJ mice. In contrast, intraperitoneal inoculation activated pulmonary natural killer cells in both mouse lines but did not activate pulmonary macrophages. PMID:6832817

  19. 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

  20. Combination effects of peramivir and favipiravir against oseltamivir-resistant 2009 pandemic influenza A(H1N1) infection in mice.

    PubMed

    Park, Sehee; Kim, Jin Il; Lee, Ilseob; 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.

  1. 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

  2. Resistance of CD-1 and ogg1 DNA repair-deficient mice to thalidomide and hydrolysis product embryopathies in embryo culture.

    PubMed

    Lee, Crystal J J; Gonçalves, Luisa L; Wells, Peter G

    2011-07-01

    Thalidomide (TD) displays remarkable species specificity, causing birth defects (teratogenesis) in humans and rabbits, but not rats or mice; yet, few determinants of species susceptibility have been identified. Also, certain mouse strains are susceptible to the embryopathic effects of some teratogens in embryo culture despite their resistance in vivo. Herein we show that CD-1 mouse embryos in culture are resistant to limb embryopathies caused by TD and two of its hydrolysis products, 2-phthalimidoglutaramic acid and 2-phthalimidoglutaric acid, although all three compounds cause these embryopathies in rabbit embryo culture. These results show that the resistance of CD-1 mice to TD teratogenesis is inherent to the embryo and is not dependent upon maternal factors, including differential in vivo exposure to the many hydrolysis products of TD. In utero TD exposure of rabbit but not mouse embryos elevates levels of the teratogenic oxidative DNA lesion 8-oxoguanine, which is repaired by oxoguanine glycosylase 1 (OGG1). However, DNA repair-deficient ogg1 knockout mice proved resistant to TD-initiated embryopathies in culture and teratogenesis in vivo, indicating that the resistance of mice is not due to a higher level of DNA repair.

  3. 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.

  4. 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

  5. [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

  6. Lead-resistant Providencia alcalifaciens strain 2EA bioprecipitates Pb+2 as lead phosphate.

    PubMed

    Naik, M M; Khanolkar, D; Dubey, S K

    2013-02-01

    A lead-resistant bacteria isolated from soil contaminated with car battery waste were identified as Providencia alcalifaciens based on biochemical characteristics, FAME profile and 16S rRNA sequencing and designated as strain 2EA. It resists lead nitrate up to 0·0014 mol l(-1) by precipitating soluble lead as insoluble light brown solid. Scanning electron microscopy coupled with energy-dispersive X-ray spectrometric analysis (SEM-EDX) and X-ray diffraction spectroscopy (XRD) revealed extracellular light brown precipitate as lead orthophosphate mineral, that is, Pb(9) (PO(4))(6) catalysed by phosphatase enzyme. This lead-resistant bacterial strain also demonstrated tolerance to high levels of cadmium and mercury along with multiple antibiotic resistance. Providencia alcalifaciens strain 2EA could be used for bioremediation of lead-contaminated environmental sites, as it can efficiently precipitate lead as lead phosphate.

  7. Development of modern InhA inhibitors to combat drug resistant strains of Mycobacterium tuberculosis.

    PubMed

    Tonge, Peter J; Kisker, Caroline; Slayden, Richard A

    2007-01-01

    Strategies for the development of novel tuberculosis chemotherapeutics against existing drug resistant strains involve the identification and inhibition of novel drug targets as well as the design and synthesis of compounds against historical targets. InhA, the enoyl reductase from the mycobacterial type II fatty acid biosynthesis pathway, is a target of the frontline chemotherapeutic, isoniazid (INH). Importantly, the majority of INH-resistant clinical isolates arise from mutations in KatG, the enzyme responsible for activating isoniazid, into its active form. Thus compounds that inhibit InhA without first requiring KatG activation will be active against the majority of INH resistant strains of Mycobacterium tuberculosis. This review describes the role of InhA in cell wall biosynthesis and recent progress in the development of novel diphenyl ether-based InhA inhibitors that have activity against both sensitive and drug resistant strains of M. tuberculosis.

  8. 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.

  9. Genotyping and Descriptive Proteomics of a Potential Zoonotic Canine Strain of Giardia duodenalis, Infective to Mice

    PubMed Central

    Coelho, Camila Henriques; Costa, Adriana Oliveira; Silva, Ana Carolina Carvalho; Pucci, Maíra Mazzoni; Serufo, Angela Vieira; Busatti, Haendel Goncalves Nogueira Oliveira; Durigan, Maurício; Perales, Jonas; Chapeaurouge, Alex; da Silva e Silva, Daniel Almeida; Gomes, Maria Aparecida; Toledo, Juliano Simões; Singer, Steven M.; Silva-Pereira, Rosiane A.; Fernandes, Ana Paula

    2016-01-01

    The zoonotic potential of giardiasis, as proposed by WHO since the late 70's, has been largely confirmed in this century. The genetic assemblages A and B of Giardia duodenalis are frequently isolated from human and canine hosts. Most of the assemblage A strains are not infective to adult mice, which can limit the range of studies regarding to biology of G. duodenalis, including virulence factors and the interaction with host immune system. This study aimed to determine the infectivity in mice of an assemblage A Giardia duodenalis strain (BHFC1) isolated from a dog and to classify the strain in sub-assemblages (AI, AII, AIII) through the phylogenetic analysis of beta-giardin (bg), triose phosphate isomerase (tpi) and glutamate dehydrogenase (gdh) genes. In addition, the proteomic profile of soluble and insoluble protein fractions of trophozoites was analyzed by 2D-electrophoresis. Accordingly, trophozoites of BHFC1 were highly infective to Swiss mice. The phylogenetic analysis of tpi and gdh revealed that BHFC1 clustered to sub-assemblage AI. The proteomic map of soluble and insoluble protein fractions led to the identification of 187 proteins of G. duodenalis, 27 of them corresponding to hypothetical proteins. Considering both soluble and soluble fractions, the vast majority of the identified proteins (n = 82) were classified as metabolic proteins, mainly associated with carbon and lipid metabolism, including 53 proteins with catalytic activity. Some of the identified proteins correspond to antigens while others can be correlated with virulence. Besides a significant complementation to the proteomic data of G. duodenalis, these data provide an important source of information for future studies on various aspects of the biology of this parasite, such as virulence factors and host and pathogen interactions. PMID:27760188

  10. Concomitant Benznidazole and Suramin Chemotherapy in Mice Infected with a Virulent Strain of Trypanosoma cruzi

    PubMed Central

    Santos, Eliziária C.; Cupertino, Marli C.; Bastos, Daniel S. S.; Klein, Raphael C.; Silva, Eduardo A. M.; Fietto, Juliana L. R.; Talvani, André; Bahia, Maria T.

    2015-01-01

    Although suramin (Sur) is suggested as a potential drug candidate in the management of Chagas disease, this issue has not been objectively tested. In this study, we examined the applicability of concomitant treatment with benznidazole (Bz) and suramin in mice infected with a virulent strain of Trypanosoma cruzi. Eighty 12-week-old male C57BL/6 mice were equally randomized in eight groups: (i) noninfected mice (negative control) and mice infected with T. cruzi Y strain receiving (ii) no treatment (positive control), (iii) Bz, 100 mg/kg of body weight per day, (iv) Sur, 20 mg/kg/day, and (v to viii) Sur, 20 mg/kg/day, combined with Bz, 100, 50, 25, or 5 mg/kg/day. Bz was administered by gavage, and Sur was administered intraperitoneally. Sur dramatically increased the parasitemia, cardiac content of parasite DNA, inflammation, oxidative tissue damage, and mortality. In response to high parasitic load in cardiac tissue, Sur stimulated the immune system in a manner typical of the acute phase of Chagas disease, increasing tissue levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and inducing a preferential IgG2a anti-T. cruzi serum pattern. When Sur and Bz were combined, the infection severity was attenuated, showing a dose-dependent Bz response. Sur therapy had a more harmful effect on the host than on the parasite and reduced the efficacy of Bz against T. cruzi infection. Considering that Sur drastically reinforced the infection evolution, potentiating the inflammatory process and the severity of cardiac lesions, the in vivo findings contradicted the in vitro anti-T. cruzi potential described for this drug. PMID:26169419

  11. Concomitant Benznidazole and Suramin Chemotherapy in Mice Infected with a Virulent Strain of Trypanosoma cruzi.

    PubMed

    Santos, Eliziária C; Novaes, Rômulo D; Cupertino, Marli C; Bastos, Daniel S S; Klein, Raphael C; Silva, Eduardo A M; Fietto, Juliana L R; Talvani, André; Bahia, Maria T; Oliveira, Leandro L

    2015-10-01

    Although suramin (Sur) is suggested as a potential drug candidate in the management of Chagas disease, this issue has not been objectively tested. In this study, we examined the applicability of concomitant treatment with benznidazole (Bz) and suramin in mice infected with a virulent strain of Trypanosoma cruzi. Eighty 12-week-old male C57BL/6 mice were equally randomized in eight groups: (i) noninfected mice (negative control) and mice infected with T. cruzi Y strain receiving (ii) no treatment (positive control), (iii) Bz, 100 mg/kg of body weight per day, (iv) Sur, 20 mg/kg/day, and (v to viii) Sur, 20 mg/kg/day, combined with Bz, 100, 50, 25, or 5 mg/kg/day. Bz was administered by gavage, and Sur was administered intraperitoneally. Sur dramatically increased the parasitemia, cardiac content of parasite DNA, inflammation, oxidative tissue damage, and mortality. In response to high parasitic load in cardiac tissue, Sur stimulated the immune system in a manner typical of the acute phase of Chagas disease, increasing tissue levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and inducing a preferential IgG2a anti-T. cruzi serum pattern. When Sur and Bz were combined, the infection severity was attenuated, showing a dose-dependent Bz response. Sur therapy had a more harmful effect on the host than on the parasite and reduced the efficacy of Bz against T. cruzi infection. Considering that Sur drastically reinforced the infection evolution, potentiating the inflammatory process and the severity of cardiac lesions, the in vivo findings contradicted the in vitro anti-T. cruzi potential described for this drug.

  12. Combinatorial Strategies for Improving Multiple-Stress Resistance in Industrially Relevant Escherichia coli Strains

    PubMed Central

    Herrgård, Markus J.

    2014-01-01

    High-cell-density fermentation for industrial production of chemicals can impose numerous stresses on cells due to high substrate, product, and by-product concentrations; high osmolarity; reactive oxygen species; and elevated temperatures. There is a need to develop platform strains of industrial microorganisms that are more tolerant toward these typical processing conditions. In this study, the growth of six industrially relevant strains of Escherichia coli was characterized under eight stress conditions representative of fed-batch fermentation, and strains W and BL21(DE3) were selected as platforms for transposon (Tn) mutagenesis due to favorable resistance characteristics. Selection experiments, followed by either targeted or genome-wide next-generation-sequencing-based Tn insertion site determination, were performed to identify mutants with improved growth properties under a subset of three stress conditions and two combinations of individual stresses. A subset of the identified loss-of-function mutants were selected for a combinatorial approach, where strains with combinations of two and three gene deletions were systematically constructed and tested for single and multistress resistance. These approaches allowed identification of (i) strain-background-specific stress resistance phenotypes, (ii) novel gene deletion mutants in E. coli that confer single and multistress resistance in a strain-background-dependent manner, and (iii) synergistic effects of multiple gene deletions that confer improved resistance over single deletions. The results of this study underscore the suboptimality and strain-specific variability of the genetic network regulating growth under stressful conditions and suggest that further exploration of the combinatorial gene deletion space in multiple strain backgrounds is needed for optimizing strains for microbial bioprocessing applications. PMID:25085490

  13. Complete Proteome of a Quinolone-Resistant Salmonella Typhimurium Phage Type DT104B Clinical Strain

    PubMed Central

    Correia, Susana; Nunes-Miranda, Júlio D.; Pinto, Luís; Santos, Hugo M.; de Toro, María; Sáenz, Yolanda; Torres, Carmen; Capelo, José Luis; Poeta, Patrícia; Igrejas, Gilberto

    2014-01-01

    Salmonellosis is one of the most common and widely distributed foodborne diseases. The emergence of Salmonella strains that are resistant to a variety of antimicrobials is a serious global public health concern. Salmonella enterica serovar Typhimurium definitive phage type 104 (DT104) is one of these emerging epidemic multidrug resistant strains. Here we collate information from the diverse and comprehensive range of experiments on Salmonella proteomes that have been published. We then present a new study of the proteome of the quinolone-resistant Se20 strain (phage type DT104B), recovered after ciprofloxacin treatment and compared it to the proteome of reference strain SL1344. A total of 186 and 219 protein spots were recovered from Se20 and SL1344 protein extracts, respectively, after two-dimensional gel electrophoresis. The signatures of 94% of the protein spots were successfully identified through matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS). Three antimicrobial resistance related proteins, whose genes were previously detected by polymerase chain reaction (PCR), were identified in the clinical strain. The presence of these proteins, dihydropteroate synthase type-2 (sul2 gene), aminoglycoside resistance protein A (strA gene) and aminoglycoside 6'-N-acetyltransferase type Ib-cr4 (aac(6')-Ib-cr4 gene), was confirmed in the DT104B clinical strain. The aac(6')-Ib-cr4 gene is responsible for plasmid-mediated aminoglycoside and quinolone resistance. This is a preliminary analysis of the proteome of these two S. Typhimurium strains and further work is being developed to better understand how antimicrobial resistance is developing in this pathogen. PMID:25196519

  14. 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

  15. 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

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

    PubMed

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

    2013-10-22

    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.

  17. 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

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

    PubMed

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

    2013-10-22

    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

  19. 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

  20. HIV Drug-resistant Strains as Epidemiologic Sentinels

    PubMed Central

    Grant, Robert M.; Porco, Travis C.; Getz, Wayne M.

    2006-01-01

    Observed declines in drug resistance to nucleoside reverse transcriptase inhibitors among persons recently infected with HIV-1 in monitored subpopulations can be interpreted as a positive sign and lead public health officials to decrease efforts towards HIV prevention. By means of a mathematical model, we identified 3 processes that can account for the observed decline: increase in high-risk behavior, decrease in proportion of acutely infected persons whose conditions are treated, and change in treatment efficacy. These processes, singly or in combination, can lead to increases or decreases in disease and drug-resistance prevalence in the general population. We discuss the most appropriate public health response under each scenario and emphasize how further data collection and analyses are required to more reliably evaluate the observed time trends and the relative importance of forces shaping the epidemic. Our study highlights how drug resistance markers can be used as epidemiologic sentinels to devise public health solutions. PMID:16494741

  1. 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

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

    PubMed

    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

  3. Analysis of antiviral resistance in the intestinal tracts of nude mice infected with a mouse adenovirus.

    PubMed

    Umehara, K; Tazume, S; Hashimoto, K

    1987-05-01

    Upon intestinal infection of heterozygous (nu/+) mice with mouse adenovirus, antiviral resistance can be seen in the form of negative-recovery of virus from feces 2-3 wks post infection. On the other hand, in similar infections in BALB/c nude (nu/nu) mice, the antiviral resistance is manifested as negative-recovery of virus from feces at a later stage, i.e., at around 6 wks post infection. This resistance was not accompanied by rises in interferon titer, rises in natural killer (NK) cell activity, nor was the resistance affected by the introduction of anti-asialo GM1 antibody. No distinct loss of resistance was observed upon administration of carrageenan, but the resistance in the group given carrageenan immediately before and after viral challenge seemed to be slightly reduced. In all infected nu/nu mice, neither neutralizing antibody (NT-Ab) nor complement-dependent NT-Ab could be detected by the usual tube method. On the other hand, a complete abolishment of the antiviral resistance was seen following cyclophosphamide administration. For clarification of the antiviral resistance factor in nu/nu mice, the analysis of antibody other than NT-Ab and complement-dependent NT-Ab, and the problem of resolution of antibody titration remain. Furthermore, it has been noted that the serum IgG titer is high in nu/nu mice and that this level is depressed by cyclophosphamide administration. It is believed that this may be in some way involved with the loss of antiviral resistance observed.

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

    PubMed

    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

    2015-04-21

    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.

  5. 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

  6. Surveillance of antimicrobial resistance in Escherichia coli strains isolated from pigs at Spanish slaughterhouses.

    PubMed

    Teshager, T; Herrero, I A; Porrero, M C; Garde, J; Moreno, M A; Domínguez, L

    2000-07-01

    Antimicrobial resistance can make the efficient treatment of bacterial infections in humans and animals more difficult. Antimicrobial use in food animals may be one of the factors contributing to resistance. The Spanish surveillance network VAV has established a baseline of antimicrobial resistance in Escherichia coli strains from healthy pigs. Minimum inhibitory concentration and patterns of resistance to antimicrobials used in animals and humans were determined for 205 faecal strains isolated in a sampling frame of four slaughterhouses in Spain from 220 pigs in 1998. Higher levels of resistance were seen against antimicrobial agents authorised for use in food animals especially tetracycline, sulphonamides, trimethoprim and amoxycillin. All isolates were susceptible to antimicrobials employed mainly in humans such as ceftazidime, cefotaxime, imipenem, aztreonam and amikacin.

  7. Surveillance of antimicrobial resistance in Escherichia coli strains isolated from pigs at Spanish slaughterhouses.

    PubMed

    Teshager, T; Herrero, I A; Porrero, M C; Garde, J; Moreno, M A; Domínguez, L

    2000-07-01

    Antimicrobial resistance can make the efficient treatment of bacterial infections in humans and animals more difficult. Antimicrobial use in food animals may be one of the factors contributing to resistance. The Spanish surveillance network VAV has established a baseline of antimicrobial resistance in Escherichia coli strains from healthy pigs. Minimum inhibitory concentration and patterns of resistance to antimicrobials used in animals and humans were determined for 205 faecal strains isolated in a sampling frame of four slaughterhouses in Spain from 220 pigs in 1998. Higher levels of resistance were seen against antimicrobial agents authorised for use in food animals especially tetracycline, sulphonamides, trimethoprim and amoxycillin. All isolates were susceptible to antimicrobials employed mainly in humans such as ceftazidime, cefotaxime, imipenem, aztreonam and amikacin. PMID:10854810

  8. 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

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

    PubMed

    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

    2015-11-25

    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.

  10. Altered protoxin activation by midgut enzymes from a Bacillus thuringiensis resistant strain of Plodia interpunctella.

    PubMed

    Oppert, B; Kramer, K J; Johnson, D E; MacIntosh, S C; McGaughey, W H

    1994-02-15

    Processing of Bacillus thuringiensis protoxins to toxins by midgut proteinases from a strain of the Indianmeal moth, Plodia interpunctella (Hubner), resistant to B. thuringiensis subspecies entomocidus (HD-198) was slower than that by midgut proteinases from the susceptible parent strain or a strain resistant to B. thuringiensis subspecies kurstaki (HD-1, Dipel). Midgut extracts from entomocidus-resistant insects exhibited five-fold lower activity toward the synthetic substrate alpha-N-benzoyl-DL-arginine rho-nitroanilide than extracts from susceptible or kurstaki-resistant insects. Midgut enzymes from susceptible or kurstaki-resistant insects converted the 133 kDa CryIA(c) protoxin to 61-63 kDa proteins, while incubations with entomocidus-resistant enzymes resulted in predominantly products of intermediate size, even with increased amounts of midgut extract. The 61-63 kDa proteins were only produced by entomocidus-resistant midgut extracts after long term incubations with the protoxin. The data suggest that altered protoxin activation by midgut proteinases is involved in some types of insect resistance to B. thuringiensis.

  11. Pheromone killing of multidrug-resistant Enterococcus faecalis V583 by native commensal strains

    PubMed Central

    Gilmore, Michael S.; Rauch, Marcus; Ramsey, Matthew M.; Himes, Paul R.; Varahan, Sriram; Manson, Janet M.; Lebreton, Francois; Hancock, Lynn Ernest

    2015-01-01

    Multidrug-resistant Enterococcus faecalis possess numerous mobile elements that encode virulence and antibiotic resistance traits as well as new metabolic pathways, often constituting over one-quarter of the genome. It was of interest to determine how this large accretion of mobile elements affects competitive growth in the gastrointestinal (GI) tract consortium. We unexpectedly observed that the prototype clinical isolate strain V583 was actively killed by GI tract flora, whereas commensal enterococci flourished. It was found that killing of V583 resulted from lethal cross-talk between accumulated mobile elements and that this cross-talk was induced by a heptapeptide pheromone produced by native E. faecalis present in the fecal consortium. These results highlight two important aspects of the evolution of multidrug-resistant enterococci: (i) the accretion of mobile elements in E. faecalis V583 renders it incompatible with commensal strains, and (ii) because of this incompatibility, multidrug-resistant strains sharing features found in V583 cannot coexist with commensal strains. The accumulation of mobile elements in hospital isolates of enterococci can include those that are inherently incompatible with native flora, highlighting the importance of maintaining commensal populations as means of preventing colonization and subsequent infection by multidrug-resistant strains. PMID:26039987

  12. RIFAMYCIN. XXXIII. ISOLATION OF ACTINOPHAGES ACTIVE ON STREPTOMYCES MEDITERRANEI AND CHARACTERISTICS OF PHAGE-RESISTANT STRAINS.

    PubMed

    THIEMANN, J E; HENGELLER, C; VIRGILIO, A; BUELLI, O; LICCIARDELLO, G

    1964-05-01

    Five actinophages highly specific for Streptomyces mediterranei were isolated from lysed broth cultures. Studies were performed on the effect of plating conditions on plaque formation. The development of phage-resistant strains of S. mediterranei not only eliminated the phage but also significantly increased rifamycin yields. The phage-resistant cultures proved to be more unstable than the original sensitive strain. Maintenance of the cultures as frozen vegetative mycelium assured culture stability and reproducibility of the results. Strict aseptic precautions throughout the laboratories and fermentation areas did not eliminate the danger of phage infection; effective control was obtained only with the introduction of resistant strains. S. mediterranei phages proved to be highly specific for calcium as an adsorption cofactor; addition of calcium-sequestering agents to sensitive mycelium completely prevented its lysis by the phage. The resistant strains developed were capable of adsorbing the phage and of releasing it without multiplication upon aging of the mycelium. No marked morphological, cultural, or biochemical differences were found among the various phage-resistant strains.

  13. [Serovars and Drug-Resistance of Salmonella Strains Isolated from Domestic Chicken Meat in Tokyo (1992-2012)].

    PubMed

    Katoh, Rei; Matsushita, Shigeru; Shimojima, Yukako; Ishitsuka, Rie; Sadamasu, Kenji; Kai, Akemi

    2015-01-01

    A total of 477 Salmonella strains isolated from retail domestic chicken meat during 1992-2012 in Tokyo, were examined regarding their serovars and drug-resistance. These strains were detected in 469 (29.8%) of 1,576 samples. The detection rate in every two years was 10.1% to 46.3% of the range. Serological typing results showed that 477 strains were classified into 22 serovars excepting 2 untypable strains. Among them, S. Infantis (312 strains) was the most prevalent, followed by II O4: b: [e, n, x] (S. II Sofia) (71 strains), S. Hadar (20 strains), S. Typhimurium (20 strains), S. Manhattan (12 strains), S. Schwarzengrund (9 strains), S. Agona (7 strains), and other 15 serovars (24 strains). Results of the antibacterial drug susceptibility test for 477 strains revealed that 89.9% was resistant to some of the 12 drugs tested, and multidrug-resistant strains accounted for 90.2% among them. The frequencies of resistance to each drug were 81.8%; 77.8%, 45.5%, 33.3%, 11.3%, 9.6%, 2.9%, 0.6%, 0.6% and 0.2%, in order with high frequency, for SM, TC, KM, ST, NA, ABPC, CP, FOM, CTX and CAZ, respectively. None of the strains was resistant to NFLX or IPM. Three CTX-resistant strains were CTX-M type extended-spectrum β-lactamase (ESBL) producers, and the group of CTX-M type ESBL genes were CTX-M-2 group (2 strains) and CTX-M-9 group (1 strain). CAZ-resistant 1 strain was an ESBL producer, but the ESBL gene was not determined. PMID:26548296

  14. Characterization of SCCmec types, antibiotic resistance, and toxin gene profiles of Staphylococcus aureus strains.

    PubMed

    Szczuka, Ewa; Grabska, Katarzyna; Trawczyński, Krzysztof; Bosacka, Karolina; Kaznowski, Adam

    2013-09-01

    Methicillin-resistant Staphylococcus aureus (MRSA) causes serious nosocomial and community acquired infections. Resistance to methicillin is mediated by the mecA gene, which is inserted in a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec). We determined the SCCmec types, the occurrence of genes encoding toxic shock syndrome toxin (tst), exfoliative toxin (eta, etb), Panton-Valentine leukocidin (pvl) as well as antibiotic susceptibility of these isolates. Among 65 hospital-acquired methicillin-resistant S. aureus (HA-MRSA) strains, SCCmec types II, III and IV were identified. Type III SCCmec was the most prevalent (62%), followed by mec types II (24%) and IV (14%). Four community acquired methicillin-resistant S. aureus (CA-MRSA) strains carried SCCmec type IV and were pvl-positive. The most prevalent gene among HA-MRSA was pvl. The toxic shock syndrome toxin and exfoliative toxin genes were found only in hospital-acquired methicillin-resistant S. aureus. The results of this study demonstrate that the SCCmec type III is predominant among strains recovered from hospitalized patients with infections and that these strains were resistant to many antibiotics used in the treatment of staphylococcal infections.

  15. Unique Structural Modifications Are Present in the Lipopolysaccharide from Colistin-Resistant Strains of Acinetobacter baumannii

    PubMed Central

    Pelletier, Mark R.; Casella, Leila G.; Jones, Jace W.; Adams, Mark D.; Zurawski, Daniel V.; Hazlett, Karsten R. O.; Doi, Yohei

    2013-01-01

    Acinetobacter baumannii is a nosocomial opportunistic pathogen that can cause severe infections, including hospital-acquired pneumonia, wound infections, and sepsis. Multidrug-resistant (MDR) strains are prevalent, further complicating patient treatment. Due to the increase in MDR strains, the cationic antimicrobial peptide colistin has been used to treat A. baumannii infections. Colistin-resistant strains of A. baumannii with alterations to the lipid A component of lipopolysaccharide (LPS) have been reported; specifically, the lipid A structure was shown to be hepta-acylated with a phosphoethanolamine (pEtN) modification present on one of the terminal phosphate residues. Using a tandem mass spectrometry platform, we provide definitive evidence that the lipid A isolated from colistin-resistant A. baumannii MAC204 LPS contains a novel structure corresponding to a diphosphoryl hepta-acylated lipid A structure with both pEtN and galactosamine (GalN) modifications. To correlate our structural studies with clinically relevant samples, we characterized colistin-susceptible and -resistant isolates obtained from patients. These results demonstrated that the clinical colistin-resistant isolate had the same pEtN and GalN modifications as those seen in the laboratory-adapted A. baumannii strain MAC204. In summary, this work has shown complete structure characterization including the accurate assignment of acylation, phosphorylation, and glycosylation of lipid A from A. baumannii, which are important for resistance to colistin. PMID:23877686

  16. 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.

  17. 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

  18. 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

    2015-01-07

    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.

  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. Sperm morphology in two house mouse subspecies: do wild-derived strains and wild mice tell the same story?

    PubMed

    Albrechtová, Jana; Albrecht, Tomáš; Ďureje, Ludovít; Pallazola, Vincent A; Piálek, Jaroslav

    2014-01-01

    Being subject to intense post-copulatory selection, sperm size is a principal determining component of male fitness. Although previous studies have presented comparative sperm size data at higher taxonomic levels, information on the evolution of sperm size within species is generally lacking. Here, we studied two house mouse subspecies, Mus musculus musculus and Mus musculus domesticus, which undergo incipient speciation. We measured four sperm dimensions from cauda epididymis smears of 28 wild-caught mice of both subspecies. As inbred mouse strains are frequently used as proxies for exploring evolutionary processes, we further studied four wild-derived inbred strains from each subspecies. The subspecies differed significantly in terms of sperm head length and midpiece length, and these differences were consistent for wild mice and wild-derived strains pooled over genomes. When the inbred strains were analyzed individually, however, their strain-specific values were in some cases significantly shifted from subspecies-specific values derived from wild mice. We conclude that: (1) the size of sperm components differ in the two house mouse subspecies studied, and that (2) wild-derived strains reflect this natural polymorphism, serving as a potential tool to identify the genetic variation driving these evolutionary processes. Nevertheless, we suggest that more strains should be used in future experiments to account for natural variation and to avoid confounding results due to reduced variability and/or founder effect in the individual strains.

  1. 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.

  2. A mouse muscle-adapted enterovirus 71 strain with increased virulence in mice.

    PubMed

    Wang, Wei; Duo, Jianying; Liu, Jiangning; Ma, Chunmei; Zhang, Lianfeng; Wei, Qiang; Qin, Chuan

    2011-09-01

    Enterovirus 71 (EV71) infections can usually cause epidemic hand, foot, and mouth disease (HFMD), and occasionally lead to aseptic meningitis, encephalitis, and polio-like illness. Skeletal muscles have been thought to be crucial for the pathogenesis of EV71-related diseases. However, little is known about the virulence of mouse muscle-adapted EV71. The EV71 0805 were subjected to four passages in the mouse muscle to generate a mouse-adapted EV71 strain of 0805a. In comparison with the parental EV71 0805, the mouse muscle-adapted EV71 0805a displayed stronger cytotoxicity against Rhabdomyosarcoma (RD) cells and more efficient replication in RD cells. Furthermore, infection with the EV71 0805a significantly inhibited the gain of body weight, accompanied by increased muscle virus load and multiple tissue distribution in the infected mouse. Histological examinations indicated that infection with the EV71 0805 did not cause obvious pathogenic lesions in mice, while infection with the muscle-adapted 0805a resulted in severe necrotizing myositis in the skeletal and cardio muscles, and intestinitis in mice on day 5 post infection. Further analysis revealed many mutations in different regions of the genome of mouse muscle-adapted virus. Collectively, these data demonstrated the mouse muscle-adapted EV71 0805a with increased virulence in mice.

  3. 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.

  4. 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.

  5. [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.

  6. High-Temperature Extensometry and PdCr Temperature-Compensated Wire Resistance Strain Gages Compared

    NASA Technical Reports Server (NTRS)

    1996-01-01

    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 approximately 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.

  7. BALB/c Mice resist infection with Bartonella bacilliformis

    PubMed Central

    Infante, Beronica; Villar, Sandra; Palma, Sandra; Merello, Jenny; Valencia, Roberto; Torres, Luis; Cok, Jamie; Ventosilla, Palmira; Manguiña, Ciro; Guerra, Humberto; Henriquez, Cesar

    2008-01-01

    Background Bartonellosis due to Bartonella bacilliformis is a highly lethal endemic and sometimes epidemic infectious disease in South America, and a serious public health concern in Perú. There is limited information on the immunologic response to B. bacilliformis infection. The objective of this research was to produce experimental infection of BALB/c mice to B. bacilliformis inoculation. Findings BALB/c mice were inoculated with 1.5, 3.0 or 4.5 × 108 live B. bacilliformis using different routes: intraperitoneal, intradermal, intranasal, and subcutaneous. Cultures of spleen, liver, and lymph nodes from one to 145 days yielded no cultivable organisms. No organs showed lesions at any time. Previously inoculated mice showed no changes in the reinoculation site. Conclusion Parenteral inoculation of live B. bacilliformis via different infection routes produced no macroscopic or microscopic organ lesions in BALB/c mice. It was not possible to isolate B. bacilliformis using Columbia blood agar from 1 to 15 days after inoculation. PMID:18957122

  8. Genome Sequence of Staphylococcus pseudintermedius Strain E140, an ST71 European-Associated Methicillin-Resistant Isolate.

    PubMed

    Moodley, Arshnee; Riley, Matthew C; Kania, Stephen A; Guardabassi, Luca

    2013-03-07

    We report the first genome sequence of the methicillin-resistant Staphylococcus pseudintermedius (MRSP) strain E140, isolated from a canine bite wound infection in Denmark. This strain represents the dominant clonal lineage associated with canine MRSP infections in Europe.

  9. 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, ...

  10. Ganglioside GM1 Deficiency in Effector T Cells From NOD Mice Induces Resistance to Regulatory T-Cell Suppression

    PubMed Central

    Wu, Gusheng; Lu, Zi-Hua; Gabius, Hans-Joachim; Ledeen, Robert W.; Bleich, David

    2011-01-01

    OBJECTIVE To detect GM1 deficiency and determine its role in effector T cells (Teffs) from NOD mice in establishing resistance to regulatory T-cell (Treg) suppression. RESEARCH DESIGN AND METHODS CD4+ and CD8+ Teffs were isolated from spleens of prediabetic NOD mice for comparison with similar cells from Balb/c, C57BL/6, and NOR mice. GM1 was quantified with thin-layer chromatography for total cellular GM1 and flow cytometry for cell-surface GM1. Suppression of Teff proliferation was determined by application of GM1 cross-linking agents or coculturing with Tregs. Calcium influx in Teffs was quantified using fura-2. RESULTS Resting and activated CD4+ and CD8+ Teffs of NOD mice contained significantly less GM1 than Teffs from the other three mouse strains tested. After activation, NOD Teffs resisted suppression by Tregs or GM1 cross-linking agents in contrast to robust suppression of Balb/c Teffs; this was reversed by preincubation of NOD Teffs with GM1. NOD Teffs also showed attenuated Ca2+ influx via transient receptor potential channel 5 (TRPC5) channels induced by GM1 cross-linking, and this, too, was reversed by elevation of Teff GM1. CONCLUSIONS GM1 deficiency occurs in NOD Teffs and contributes importantly to failed suppression, which is rectified by increasing Teff GM1. Such elevation also reverses subthreshold Ca2+ influx via TRPC5 channels, an essential aspect of suppression. Our results also support a critical role for galectin-1 as a GM1 cross-linking counter-receptor that fittingly is upregulated and released by Tregs during activation. These findings suggest a novel mechanism by which pathogenic Teffs evade regulatory suppression, thereby leading to autoimmune β-cell destruction and type 1 diabetes. PMID:21788572

  11. Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance.

    PubMed

    Desjardins, Christopher A; Cohen, Keira A; Munsamy, Vanisha; Abeel, Thomas; Maharaj, Kashmeel; Walker, Bruce J; Shea, Terrance P; Almeida, Deepak V; Manson, Abigail L; Salazar, Alex; Padayatchi, Nesri; O'Donnell, Max R; Mlisana, Koleka P; Wortman, Jennifer; Birren, Bruce W; Grosset, Jacques; Earl, Ashlee M; Pym, Alexander S

    2016-05-01

    A more complete understanding of the genetic basis of drug resistance in Mycobacterium tuberculosis is critical for prompt diagnosis and optimal treatment, particularly for toxic second-line drugs such as D-cycloserine. Here we used the whole-genome sequences from 498 strains of M. tuberculosis to identify new resistance-conferring genotypes. By combining association and correlated evolution tests with strategies for amplifying signal from rare variants, we found that loss-of-function mutations in ald (Rv2780), encoding L-alanine dehydrogenase, were associated with unexplained drug resistance. Convergent evolution of this loss of function was observed exclusively among multidrug-resistant strains. Drug susceptibility testing established that ald loss of function conferred resistance to D-cycloserine, and susceptibility to the drug was partially restored by complementation of ald. Clinical strains with mutations in ald and alr exhibited increased resistance to D-cycloserine when cultured in vitro. Incorporation of D-cycloserine resistance in novel molecular diagnostics could allow for targeted use of this toxic drug among patients with susceptible infections. PMID:27064254

  12. Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance

    PubMed Central

    Desjardins, Christopher A.; Cohen, Keira A.; Munsamy, Vanisha; Abeel, Thomas; Maharaj, Kashmeel; Walker, Bruce J.; Shea, Terrance P.; Almeida, Deepak V.; Manson, Abigail L.; Salazar, Alex; Padayatchi, Nesri; O’Donnell, Max R.; Mlisana, Koleka P.; Wortman, Jennifer; Birren, Bruce W.; Grosset, Jacques; Earl, Ashlee M.; Pym, Alexander S.

    2016-01-01

    A more complete understanding of the genetic basis of drug resistance in Mycobacterium tuberculosis is critical for prompt diagnosis and optimal treatment, particularly for toxic second-line drugs like D-cycloserine. Here, we used whole-genome sequences from 498 strains of M. tuberculosis to identify novel resistance-conferring genotypes. By combining association and correlated evolution tests with strategies for amplifying signal from rare variants, we found that loss-of-function mutations in ald (Rv2780), encoding L-alanine dehydrogenase, were associated with unexplained drug resistance. Convergent evolution of this loss-of-function was observed exclusively among multidrug-resistant strains. Drug susceptibility testing established that ald loss-of-function conferred resistance to D-cycloserine, and susceptibility to the drug was partially restored by complementation of ald. Clinical strains with mutations in ald and alr exhibited increased resistance to D-cycloserine when cultured in vitro. Incorporation of D-cycloserine resistance in novel molecular diagnostics could allow for targeted utilization of this toxic drug among patients with susceptible infections. PMID:27064254

  13. Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance.

    PubMed

    Desjardins, Christopher A; Cohen, Keira A; Munsamy, Vanisha; Abeel, Thomas; Maharaj, Kashmeel; Walker, Bruce J; Shea, Terrance P; Almeida, Deepak V; Manson, Abigail L; Salazar, Alex; Padayatchi, Nesri; O'Donnell, Max R; Mlisana, Koleka P; Wortman, Jennifer; Birren, Bruce W; Grosset, Jacques; Earl, Ashlee M; Pym, Alexander S

    2016-05-01

    A more complete understanding of the genetic basis of drug resistance in Mycobacterium tuberculosis is critical for prompt diagnosis and optimal treatment, particularly for toxic second-line drugs such as D-cycloserine. Here we used the whole-genome sequences from 498 strains of M. tuberculosis to identify new resistance-conferring genotypes. By combining association and correlated evolution tests with strategies for amplifying signal from rare variants, we found that loss-of-function mutations in ald (Rv2780), encoding L-alanine dehydrogenase, were associated with unexplained drug resistance. Convergent evolution of this loss of function was observed exclusively among multidrug-resistant strains. Drug susceptibility testing established that ald loss of function conferred resistance to D-cycloserine, and susceptibility to the drug was partially restored by complementation of ald. Clinical strains with mutations in ald and alr exhibited increased resistance to D-cycloserine when cultured in vitro. Incorporation of D-cycloserine resistance in novel molecular diagnostics could allow for targeted use of this toxic drug among patients with susceptible infections.

  14. Genotypic and phenotypic characteristics of tunisian isoniazid-resistant Mycobacterium tuberculosis strains.

    PubMed

    Soudani, Alya; Hadjfredj, Sondess; Zribi, Meriem; Messaadi, Feriel; Messaoud, Taieb; Masmoudi, Afef; Zribi, Mohamed; Fendri, Chedlia

    2011-06-01

    Forty three isoniazid (INH)-resistant Mycobacterium tuberculosis isolates were characterized on the basis of the most common INH associated mutations, katG315 and mabA -15C→T, and phenotypic properties (i.e. MIC of INH, resistance associated pattern, and catalase activity). Typing for resistance mutations was performed by Multiplex Allele-Specific PCR and sequencing reaction. Mutations at either codon were detected in 67.5% of isolates: katG315 in 37.2, mabA -15C→T in 27.9 and both of them in 2.4%, respectively. katG sequencing showed a G insertion at codon 325 detected in 2 strains and leading to amino acid change T326D which has not been previously reported. Distribution of each mutation, among the investigated strains, showed that katG S315T was associated with multiple-drug profile, high-level INH resistance and loss or decreased catalase activity; whereas the mabA -15C→T was more prevalent in mono-INH resistant isolates, but it was not only associated with a low-level INH resistance. It seems that determination of catalase activity aids in the detection of isolates for which MICs are high and could, in conjunction with molecular methods, provide rapid detection of most clinical INH-resistant strains.

  15. [MOLECULAR CHARACTERISTICS OF THE MULTIDRUG-RESISTANT MYCOBACTERIUM TUBERCULOSIS STRAINS IN THE NORTHWEST RUSSIA].

    PubMed

    Vyazovaya, A A; Mokrousov, I V; Zhuravlev, V Yu; Solovieva, N S; Otten, T F; Manicheva, O A; Vishnevsky, B I; Narvskaya, O V

    2016-01-01

    The goal of this work was to study the genotypic characteristics of the multidrug-resistant (MDR, i.e., resistant to at least rifampicine and isoniazid) Mycobacterium tuberculosis strains isolated in 2011-2012 from tuberculosis (TB) patients in the Northwest Russia. Spoligotyping of 195 M. tuberculosis isolates identified 14 different spoligotypes and assigned isolates to the genetic families Beijing (n = 162, 83%), LAM (n = 15), H3/URAL (n = 14), as well as T, Haarlem and X. Spoligotypes SIT1 (Beijing), SIT42 (LAM) and SIT262 (H3/URAL) were the most prevalent. Irrespective to the genotype, all the isolates were resistant to streptomycin. The multidrug resistance was accompanied by the resistance to ethionamide (56%), amikacin (31%), kanamycin (40%), and capreomycin (33%). The ethambutol resistance was found in 71% (n = 115) and 42% (n = 14) of the Beijing and non-Beijing strains, respectively (p < 0.05). In conclusion, the multidrug resistant M. tuberculosis population circulating in the Northwest Russia continues to be dominated by the Beijing family strains.

  16. Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice.

    PubMed

    Patick, A K; Pease, L R; David, C S; Rodriguez, M

    1990-11-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination.

  17. Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice.

    PubMed Central

    Patick, A K; Pease, L R; David, C S; Rodriguez, M

    1990-01-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination. Images PMID:2214025

  18. 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

  19. 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

  20. Stability of transgene methylation patterns in mice: position effects, strain specificity and cellular mosaicism.

    PubMed

    Koetsier, P A; Mangel, L; Schmitz, B; Doerfler, W

    1996-07-01

    The methylation status of a transgene, which carried the adenovirus type 2 E2A late promoter linked to the chloramphenicol acetyltransferase gene, was studied in three transgenic mouse lines (5-8, 7-1 and 8-1). These lines were analysed over a large number of offspring generations beyond the founder animal. In mating experiments, the influence of the parent-of-origin and strain-specific backgrounds on the transgene methylation patterns were assessed and found to have no effect on the pre-established methylation patterns in mouse lines 5-8 and 8-1. The founder animal 7-1 carried two groups of a total of ten transgenes, which were located on two different chromosomes. These arrays of transgenes could be segregated into separate mouse lines 7-1A and 7-1B. The transgenes of 7-1A animals exhibited cellular mosaic methylation patterns that were demethylated in approximately 10% of the offspring in a mixed genetic background. Upon further transmission of these transgenes in a mixed genetic background, the grandparental methylation patterns were reestablished in most progeny. Mating to inbred DBA/2 mice resulted in maintenance of the demethylated pattern or in further demethylation of the transgenes in approximately 50% of the offspring. In contrast, an equal number of transgenic siblings from matings to C57BL/6 mice showed a return to the original methylation pattern. The mosaic methylation status of this locus was apparently controlled by mouse-strain-specific factors. The methylation patterns of the 7-1B transgenes were not cellular mosaic and remained stable in all offspring, as with lines 5-8 and 8-1. Hence, the strain-dependent and cellular mosaic transgene methylation patterns of 7-1A animals were probably a consequence of the chromosomal integration site of the transgenes (position effect).

  1. Lactate dehydrogenase activity in Bacteroides fragilis group strains with induced resistance to metronidazole.

    PubMed

    Presečki Stanko, Aleksandra; Sóki, Jozsef; Varda Brkić, Dijana; Plečko, Vanda

    2016-06-01

    The aims of this study were to induce in vitro metronidazole resistance in nim-negative Bacteroides fragilis group strains and to determine the lactate dehydrogenase (LDH) activity of the induced strains. A collection of B. fragilis group strains were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Minimum inhibitory concentrations (MICs) for metronidazole were determined by the agar dilution technique. The presence of nim genes was screened by PCR. A sample of 52 nim-negative metronidazole-susceptible strains were selected at random and were exposed to metronidazole in the resistance induction experiment. LDH activity was measured by spectrophotometry. Of the 52 selected strains, 12 (23.1%) acquired resistance to metronidazole. MICs ranged from 8mg/L to 96mg/L. Eight of the twelve induced strains displayed decreased LDH activity, whilst only one expressed a significant increase in LDH activity with LDH values of 49.1U/mg and 222.0U/mg, respectively. In conclusion, in vitro induction of metronidazole resistance could be selected in nim-negative B. fragilis group strains. A statistically significant decrease in LDH activity was in contrast to previous findings in which, underlying higher metronidazole MICs, an increase in LDH activity compensated for the decreased activity of pyruvate-ferredoxin oxidoreductase (PFOR). These findings could be explained if the induction caused only physiological and not genetic changes. We believe that genetic mutations in the B. fragilis strain that demonstrated an emergent increase in LDH activity were responsible for the increased activity. PMID:27436459

  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. 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

  4. In vivo-selected mutations in methyl-directed mismatch repair suppress the virulence attenuation of Salmonella dam mutant strains following intraperitoneal, but not oral, infection of naïve mice.

    PubMed

    Heithoff, Douglas M; Badie, Golnaz; Julio, Steven M; Enioutina, Elena Y; Daynes, Raymond A; Sinsheimer, Robert L; Mahan, Michael J

    2007-07-01

    Salmonella enterica serovar Typhimurium that lacks the DNA adenine methylase (Dam) ectopically expresses multiple genes that are preferentially expressed during infection, is attenuated for virulence, and confers heightened immunity in vaccinated hosts. The safety of dam mutant Salmonella vaccines was evaluated by screening within infected mice for isolates that have an increased capacity to cause disease relative to the attenuated parental strain. Since dam mutant strains are sensitive to the DNA base analog 2-aminopurine (2-AP), we screened for 2-AP-resistant (2-AP(r)) isolates in systemic tissues of mice infected with dam mutant Salmonella. Such 2-AP(r) derivatives were isolated following intraperitoneal but not oral administration and were shown to be competent for infectivity via intraperitoneal but not oral infection of naïve mice. These 2-AP(r) derivatives were deficient in methyl-directed mismatch repair and were resistant to nitric oxide, yet they retained the bile-sensitive phenotype of the parental dam mutant strain. Additionally, introduction of a mutH null mutation into dam mutant cells suppressed the inherent defects in intraperitoneal infectivity and nitric oxide resistance, as well as overexpression of SpvB, an actin cytotoxin required for Salmonella systemic survival. These data suggest that restoration of intraperitoneal virulence of dam mutant strains is associated with deficiencies in methyl-directed mismatch repair that correlate with the production of systemically related virulence functions.

  5. Susceptibilities of ampicillin-resistant strains of Salmonella other than S. typhi to 10 antimicrobial agents.

    PubMed Central

    Alós, J I; Gómez-Garcés, J L; Cogollos, R; Amor, E; Pérez-Rivilla, A

    1992-01-01

    Ampicillin-resistant strains of Salmonella other than S. typhi constitute a health problem. We tested the antimicrobial susceptibilities to 10 antibiotics of 57 of these strains isolated in a 30-month period. The rates of resistance were as follows: chloramphenicol, 40.3%; tetracycline, 33.3%; gentamicin, 5.3%; co-trimoxazole, 5.3%; nalidixic acid, 1.8%; and amoxicillin-clavulanic acid, cefotaxime, ceftriaxone, aztreonam, and ciprofloxacin, 0%. In our experience, there are alternative antibiotics with excellent in vitro activities. PMID:1416869

  6. Survey of methicillin-resistant Staphylococcus aureus strains from two hospitals in El Paso, Texas.

    PubMed

    O'Brien, Frances G; Lim, Tien Tze; Winnett, David C; Coombs, Geoffrey W; Pearson, Julie C; Delgado, Alejandro; Langevin, Mark J; Cantore, Stephanie A; Gonzalez, Leti; Gustafson, John E

    2005-06-01

    Seventy-one percent of 76 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from two medical centers in El Paso, Texas, represent three similar pulsed-field gel electrophoresis types. Overall, six pulsed-field types were identified represented by multilocus sequence/staphylococcal chromosomal cassette DNA mec (SCCmec) types: ST5-MRSA-II; ST36-MRSA-II; ST8 (untypeable SCCmec); and a newly described clonal cluster 8 strain, ST507-MRSA-IV. This study demonstrates the presence of multiple-antibiotic-resistant epidemic MRSA clones in El Paso.

  7. The FVB/N mice: A well suited strain to study learning and memory processes using olfactory cues.

    PubMed

    Girard, Stéphane D; Escoffier, Guy; Khrestchatisky, Michel; Roman, François S

    2016-01-01

    The FVB/N mice are well suited to generate transgenic animals. These mice are also particularly sensitive to seizures and neurodegeneration induced by systemic administration of chemoconvulsants and are very useful to model epilepsy. However, previous studies report strong cognitive and visual impairments suggesting this background unsuitable for behavioral analysis. In this study, we assessed and compared learning abilities of FVB/N mice to the well characterized C57BL/6 strain using the olfactory tubing maze, a non-visual hippocampus-dependent task in which the mice were trained to learn odor-reward associations. Exploratory behavior and spontaneous locomotor activity were then compared using the open field test. We demonstrated that FVB/N mice were able to learn the task, reaching at the end of the test a high percentage of correct responses. Interestingly, the performance of the FVB/N mice was at least similar to that of the C57BL/6 mice. Moreover, in contrast to previous reports, the FVB/N mice displayed a spontaneous locomotor activity lower than C57BL/6 mice. Our study demonstrated that FVB/N mice are not cognitively impaired and that their learning and memory performance can be assessed when the task is based on olfaction rather than vision.

  8. [Antibiotic resistance and biofilm formation in Staphylococcus saprophyticus strains isolated from urine].

    PubMed

    Cernohorská, L; Votava, M

    2010-04-01

    Eighty-seven Staphylococcus saprophyticus strains isolated from urine of 87 patients with cystitis were examined in 2005-2009. All strains were tested for resistance to vancomycin, nitrofurantoin, doxycycline, oxacillin, amoxicillin/clavulanate, cefoxitin and sulfamethoxazole/trimethoprim and for biofilm formation by a modified Christensen method. None of the tested strains of S. saprophyticus showed resistance to vancomycin, while 2 strains (2.3 %) were resistant to nitrofurantoin, 9 (10.3%) to doxycycline, 20 (23.0 %) to oxacillin, 6 (6.9%) to amoxicillin/clavulanate, 6 (6.9%) to cefoxitin and 1 (1.1%) to sulfamethoxazole/trimethoprim. S. saprophyticus was detected as the causative agent of cystitis in 0.4 % of 20,375 culture positive urine samples analyzed in our laboratory between 2005 and 2009. Most 67 (77.0%) S. saprophyticus strains were recovered from women, particularly from young women. Biofilm formation was detected in 16 (18.4 %) out of 87 S. saprophyticus strains.

  9. 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

  10. Import and efflux of flubendazole in Haemonchus contortus strains susceptible and resistant to anthelmintics.

    PubMed

    Bártíková, Hana; Vokřál, Ivan; Kubíček, Vladimír; Szotáková, Barbora; Prchal, Lukáš; Lamka, Jiří; Várady, Marián; Skálová, Lenka

    2012-07-01

    Drug entry into the body of a helminth is a key factor in the efficacy of anthelmintics. The present project was designed to study the ex vivo uptake and efflux of the benzimidazole anthelmintic flubendazole (FLU) in four strains of H. contortus: the ISE strain (fully susceptible to anthelmintics), the ISE-S strain (resistant to ivermectin), the BR strain (resistant to benzimidazoles) and the WR strain (multi-resistant). The transport of FLU between dead and living nematodes was also compared as well as the effect of verapamil, an inhibitor of the main efflux ABCB1 transporter (P-glycoprotein), on FLU accumulation in nematodes. The obtained results showed that FLU is able to effectively enter H. contortus adults due to high FLU lipophilicity. Passive diffusion is probably the only mechanism in both FLU import and efflux from nematodes. No differences in FLU transport were found among four H. contortus strains with different sensitivity to anthelmintics. No active FLU efflux from H. contortus and no effect of verapamil were observed, indicating that H. contortus cannot protect itself against FLU by the active removal of this anthelmintic from its body.

  11. 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

  12. Neurochemical Measurement of Adenosine in Discrete Brain Regions of Five Strains of Inbred Mice

    PubMed Central

    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

  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. 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.

  15. Identification of Resistance to Wet Bubble Disease and Genetic Diversity in Wild and Cultivated Strains of Agaricus bisporus.

    PubMed

    Fu, Yongping; Wang, Xinxin; Li, Dan; Liu, Yuan; Song, Bing; Zhang, Chunlan; Wang, Qi; Chen, Meiyuan; Zhang, Zhiwu; Li, Yu

    2016-01-01

    Outbreaks of wet bubble disease (WBD) caused by Mycogone perniciosa are increasing across the world and seriously affecting the yield of Agaricus bisporus. However, highly WBD-resistant strains are rare. Here, we tested 28 A. bisporus strains for WBD resistance by inoculating M. perniciosa spore suspension on casing soil, and assessed genetic diversity of these strains using 17 new simple sequence repeat (SSR) markers developed in this study. We found that 10 wild strains originating from the Tibetan Plateau in China were highly WBD-resistant strains, and 13 cultivated strains from six countries were highly susceptible strains. A total of 88 alleles were detected in these 28 strains, and the observed number of alleles per locus ranged from 2 to 8. Cluster and genetic structure analysis results revealed the wild resources from China have a relatively high level of genetic diversity and occur at low level of gene flow and introgression with cultivated strains. Moreover, the wild strains from China potentially have the consensus ancestral genotypes different from the cultivated strains and evolved independently. Therefore, the highly WBD-resistant wild strains from China and newly developed SSR markers could be used as novel sources for WBD-resistant breeding and quantitative trait locus (QTL) mapping of WBD-resistant gene of A. bisporus. PMID:27669211

  16. Identification of Resistance to Wet Bubble Disease and Genetic Diversity in Wild and Cultivated Strains of Agaricus bisporus

    PubMed Central

    Fu, Yongping; Wang, Xinxin; Li, Dan; Liu, Yuan; Song, Bing; Zhang, Chunlan; Wang, Qi; Chen, Meiyuan; Zhang, Zhiwu; Li, Yu

    2016-01-01

    Outbreaks of wet bubble disease (WBD) caused by Mycogone perniciosa are increasing across the world and seriously affecting the yield of Agaricus bisporus. However, highly WBD-resistant strains are rare. Here, we tested 28 A. bisporus strains for WBD resistance by inoculating M. perniciosa spore suspension on casing soil, and assessed genetic diversity of these strains using 17 new simple sequence repeat (SSR) markers developed in this study. We found that 10 wild strains originating from the Tibetan Plateau in China were highly WBD-resistant strains, and 13 cultivated strains from six countries were highly susceptible strains. A total of 88 alleles were detected in these 28 strains, and the observed number of alleles per locus ranged from 2 to 8. Cluster and genetic structure analysis results revealed the wild resources from China have a relatively high level of genetic diversity and occur at low level of gene flow and introgression with cultivated strains. Moreover, the wild strains from China potentially have the consensus ancestral genotypes different from the cultivated strains and evolved independently. Therefore, the highly WBD-resistant wild strains from China and newly developed SSR markers could be used as novel sources for WBD-resistant breeding and quantitative trait locus (QTL) mapping of WBD-resistant gene of A. bisporus. PMID:27669211

  17. 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

  18. Timp3 Deficient Mice Show Resistance to Developing Breast Cancer

    PubMed Central

    Jackson, Hartland W.; Hojilla, Carlo V.; Weiss, Ashley; Sanchez, Otto H.; Wood, Geoffrey A.; Khokha, Rama

    2015-01-01

    Timp3 is commonly silenced in breast cancer, but mechanistic studies have identified both tumor promotion and suppression effects of this gene. We have taken a genetic approach to determine the impact of Timp3 loss on two mouse models of breast cancer. Interestingly, MMTV-PyMT Timp3−⁄− mice have delayed tumor onset and 36% of MMTV-Neu Timp3−⁄− mice remain tumor free. TIMP3 is a regulator of TNF signaling and similar to Timp3, Tnf or Tnfr1 loss delays early tumorigenesis. The tumor suppression in Timp3 null mice requires Tnfr1, but does not result in alterations in the local immune compartment. In the mammary gland, Timps are highly expressed in the stroma and through the transplantation of tumor cells we observe that Timp3 deficiency in the host is sufficient to delay the growth of early, but not advanced tumor cells. Together our data is the first to identify a tumor promoting role of endogenous Timp3 in vivo, the spatial and temporal windows of this effect, and its dependence on Tnfr1. PMID:25807548

  19. High-Efficiency Generation of Antibiotic-Resistant Strains of Streptococcus pneumoniae by PCR and Transformation

    PubMed Central

    Martín-Galiano, Antonio J.; de la Campa, Adela G.

    2003-01-01

    We designed a method by which to generate antibiotic-resistant strains of Streptococcus pneumoniae at frequencies 4 orders of magnitude greater than the spontaneous mutation rate. The method is based on the natural ability of this organism to be genetically transformed with PCR products carrying sequences homologous to its chromosome. The genes encoding the targets of ciprofloxacin (parC, encoding the ParC subunit of DNA topoisomerase IV), rifampin (rpoB, encoding the β subunit of RNA polymerase), and streptomycin (rpsL, encoding the S12 ribosomal protein) from susceptible laboratory strain R6 were amplified by PCR and used to transform the same strain. Resistant mutants were obtained with a frequency of 10−4 to 10−5, depending on the fidelity of the DNA polymerase used for PCR amplifications. Ciprofloxacin-resistant mutants, for which the MICs were four-to eightfold higher than that for R6, carried a single mutation of a residue in the quinolone resistance-determining region: S79 (change to A, F, or Y) or D83 (change to N or V). Rifampin-resistant strains, for which the MICs were at least 133-fold higher than that for R6, contained a single mutation within cluster I of rpoB: S482 (change to P), Q486 (change to L), D489 (change to V), or H499 (change to L or Y). Streptomycin-resistant mutants, for which the MICs were at least 64-fold higher than that for R6, carried a mutation at either K56 (change to I, R, or T) or K101 (change to E). PCR products obtained from the mutants were able to transform R6 to resistance with high efficiency (>104). This method could be used to efficiently obtain resistant mutants for any drug whose target is known. PMID:12654655

  20. 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

  1. An approach to identifying drug resistance associated mutations in bacterial strains

    PubMed Central

    2012-01-01

    Background Drug resistance in bacterial pathogens is an increasing problem, which stimulates research. However, our understanding of drug resistance mechanisms remains incomplete. Fortunately, the fast-growing number of fully sequenced bacterial strains now enables us to develop new methods to identify mutations associated with drug resistance. Results We present a new comparative approach to identify genes and mutations that are likely to be associated with drug resistance mechanisms. In order to test the approach, we collected genotype and phenotype data of 100 fully sequenced strains of S. aureus and 10 commonly used drugs. Then, applying the method, we re-discovered the most common genetic determinants of drug resistance and identified some novel putative associations. Conclusions Firstly, the collected data may help other researchers to develop and verify similar techniques. Secondly, the proposed method is successful in identifying drug resistance determinants. Thirdly, the in-silico identified genetic mutations, which are putatively involved in drug resistance mechanisms, may increase our understanding of the drug resistance mechanisms. PMID:23281931

  2. Neonatal infections due to multi-resistant strains: Epidemiology, current treatment, emerging therapeutic approaches and prevention.

    PubMed

    Tzialla, Chryssoula; Borghesi, Alessandro; Pozzi, Margherita; Stronati, Mauro

    2015-12-01

    Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units. The benefits of antibiotic therapy when indicated are clearly enormous, but the continued and widespread use of antibiotics has generated over the years a strong selective pressure on microorganisms, favoring the emergence of resistant strains. Health agencies worldwide are galvanizing attention toward antibiotic resistance in gram-positive and gram-negative bacteria. Infections in neonatal units due to multidrug and extensively multidrug resistant bacteria are rising and are already seriously challenging antibiotic treatment options. While there is a growing choice of agents against multi-resistant gram-positive bacteria, new options for multi-resistant gram-negative bacteria in the clinical practice have decreased significantly in the last 20 years making the treatment of infections caused by multidrug-resistant pathogens challenging mostly in neonates. Treatment options are currently limited and will be some years before any new treatment for neonates become available for clinical use, if ever. The aim of the review is to highlight the current knowledge on antibiotic resistance in the neonatal population, the possible therapeutic choices, and the prevention strategies to adopt in order to reduce the emergency and spread of resistant strains.

  3. Transplantation resistance of drug-treated hybrid or allogeneic mice against murine lymphomas. I. Immunopharmacology studies.

    PubMed

    Bonmassar, A; Riccardi, C; Rivosecchi-Merletti, P; Goldin, A; Bonmassar, E

    1980-12-15

    Sequential treatment of mice with non-lethal doses of 5(3,3'-dimethyl-l-triazeno)-imidazole-4-carboxamide (DTIC) and cyclophosphamide (Cy) was found to produce long-term inhibition of endogenous cell proliferation in the spleen and profound impairment of classical allograft responses, similar to that detectable in lethally irradiated mice. Studies were carried out with drug-treated (i.e. treated with DTIC + Cy) conventional or nude mice inoculated with lymphoma cells homozygous for the H-2b or H-2d haplotype. Transplantation resistance in various tumour-host combinations was studied in terms of survival times after tumor challenge or lymphoma cell proliferation in spleen and liver, measured by the uptake of DNA precursor 125I-labelled 5-iodo-2'-deoxyuridine ([125I]dUrd). The results of in vivo transplantation immunity tests or in vitro tests of generation of cytotoxic lymphocytes confirmed that classical T-dependent allograft responses were abrogated by drug treatment of H-2-incompatible hosts. However, localized resistance against lymphoma graft, mainly at spleen level, was found in drug-treated hybrid mice, or conventional and "nude" allogeneic recipients, as judged by [123I]dUrd uptake inhibition. Resistance presumably regulated, at least in part by the Hh (hemopoietic histocompatibility) system, was abrogated by pretreatment with carrageenan, an antimacrophage agent. In addition, treatment with DTIC + Cy did not abrogate NK activity of mice when the in vitro cytotoxicity test was conducted 5 h after Cy administration, i.e. at the time used for tumor challenge in vivo. It was concluded that selected immunological functions (i.e., antilymphoma natural resistance insensitive to DTIC + Cy, called drug-resistant inhibition of tumors, DRIT) possibly of non-T origin, similar to those detectable in lethally-irradiated mice, can be retained by hosts subjected to high doses of certain anti-tumor agents.

  4. Antidepressant-Like Effects of Central BDNF Administration in Mice of Antidepressant Sensitive Catalepsy (ASC) Strain.

    PubMed

    Tikhonova, Maria; Kulikov, Alexander V

    2012-08-31

    Although numerous data evidence the implication of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression, the potential for BDNF to correct genetically defined depressive-like states is poorly studied. This study was aimed to reveal antidepressant-like effects of BDNF (300 ng, 2×, i.c.v.) on behavior and mRNA expression of genes associated with depression-like state in the brain in mice of antidepressant sensitive catalepsy (ASC) strain characterized by high hereditary predisposition to catalepsy and depressive-like features. Behavioral tests were held on the 7th-16th days after the first (4th-13th after the second) BDNF injection. Results showed that BDNF normalized impaired sexual motivation in the ASC males, and this BDNF effect differed, with advantageous effects, from that of widely used antidepressants. The anticataleptic effect of two BDNF injections was enhanced compared with a single administration. A tendency to decrease the immobility duration in tail-suspension test was observed in BDNF-treated ASC mice. The effects on catalepsy and sexual motivation were specific since BDNF did not alter locomotor and exploratory activity or social interest in the ASC mice. Along with behavioral antidepressant-like effects on the ASC mice, BDNF increased hippocampal mRNA levels of Bdnf and Creb1 (cAMP response element-binding protein gene). BDNF also augmented mRNA levels of Arc gene encoding Arc (Activity-regulated cytoskeleton-associated) protein involved in BDNF-induced processes of neuronal and synaptic plasticity in hippocampus and prefrontal cortex. The data suggest that: [1] BDNF is effective in the treatment of some genetically defined behavioral disturbances; [2] BDNF influences sexually-motivated behavior; [3] Arc mRNA levels may serve as a molecular marker of BDNF physiological activity associated with its long-lasting behavioral effects; [4] ASC mouse strain can be used as a suitable model to study mechanisms of BDNF effects on

  5. 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

  6. 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.

  7. Distribution of mec regulator genes in methicillin-resistant Staphylococcus clinical strains.

    PubMed Central

    Suzuki, E; Kuwahara-Arai, K; Richardson, J F; Hiramatsu, K

    1993-01-01

    The distributions of the mec regulator genes mecI and mecR1, which were identified on the chromosome of mecA-carrying Staphylococcus aureus N315, in methicillin-resistant staphylococci isolated in Japan and various countries were studied. Screening by dot blot hybridization by using polymerase chain reaction (PCR)-amplified probes revealed that at least the 5'-end region of the mecR1 gene was present in all strains tested, whereas about 40% of the strains were negative for the mecI gene. The data suggested that these regulator genes were the original components of the additional mec region DNA of methicillin-resistant S. aureus as well as methicillin-resistant, coagulase-negative staphylococci of seven staphylococcal species (S. epidermidis, S. haemolyticus, S. hominis, S. sciuri, S. capitis, S. caprae, and S. warneri). The mecI gene, which presumably codes for the repressor protein of the mecA gene, was found to harbor a point mutation in all six mecI-positive methicillin-resistant S. aureus strains, and their basal level of mecA gene transcription was elevated compared with that of strain N315, which harbors a presumably intact counterpart of the mecI gene. The data suggested that the mecI gene encodes for a strong repressor function on mecA gene transcription and is deleted or mutated in clinical methicillin-resistant S. aureus strains with high levels of resistance to methicillin. Images PMID:8328773

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Acquisition of a natural resistance gene renders a clinical strain of methicilin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid

    PubMed Central

    Toh, Seok-Ming; Xiong, Liqun; Arias, Cesar A.; Villegas, Maria V.; Lolans, Karen; Quinn, John; Mankin, Alexander S.

    2009-01-01

    Linezolid, which targets the ribosome, is a new synthetic antibiotic that is used for treatment of infections caused by Gram-positive pathogens. Clinical resistance to linezolid, so far, has been developing only slowly and has involved exclusively target site mutations. We have discovered that linezolid resistance in a methicillin-resistant Staphylococcus aureus hospital strain from Colombia is determined by the presence of the cfr gene whose product, Cfr methyltransferase, modifies adenosine at position 2503 in 23S rRNA in the large ribosomal subunit. The molecular model of the linezolid-ribosome complex reveals localization of A2503 within the drug-binding site. The natural function of cfr likely involves protection against natural antibiotics whose site of action overlaps that of linezolid. In the chromosome of the clinical strain, cfr is linked to ermB, a gene responsible for dimethylation of A2058 in 23S rRNA. Co-expression of these two genes confers resistance to all the clinically-relevant antibiotics that target the large ribosomal subunit. The association of the ermB/cfr operon with transposon and plasmid genetic elements indicate its possible mobile nature. This is the first example of clinical resistance to the synthetic drug linezolid which involves a natural resistance gene with the capability of disseminating among Gram-positive pathogenic strains. PMID:17555436

  13. Preventive effects of jujube polysaccharides on fructose-induced insulin resistance and dyslipidemia in mice.

    PubMed

    Zhao, Yan; Yang, Xingbin; Ren, Daoyuan; Wang, Dongying; Xuan, Yang

    2014-08-01

    High fructose intake is associated with adverse metabolic syndromes. This study was designed to investigate whether the polysaccharides derived from Zizyphus jujube cv. Shaanbeitanzao (ZSP) could alleviate high fructose-induced insulin resistance and dyslipidemia in mice. ZSP was identified by capillary zone electrophoresis as an acidic heteropolysaccharide with l-arabinose, d-galactose and d-galacturonic acid being the main component monosaccharides. Mice were provided with 20% high-fructose water and ZSP was administered intragastrically at doses of 0, 200 or 400 mg kg(-1) BW for 4 weeks. Fructose-treated mice showed hyperglycemia, hyperinsulinemia and dyslipidemia with impaired insulin sensitivity (p < 0.05). Administration of ZSP at a dose of 400 mg kg(-1) BW significantly reduced the serum levels of glucose, insulin, TC, TG, LDL-C, and VLDL-C (p < 0.01). ZSP also markedly improved the HDL-C level, homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), and decreased the atherogenic index (AI) of the mice exposed to high-fructose water. Histopathological test with H&E and oil red O staining confirmed liver steatosis induced by a high-fructose diet and the hepatoprotective effect of ZSP. These findings indicate that the jujube polysaccharides may ameliorate insulin resistance and dyslipidemia in fructose-treated mice.

  14. 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

  15. 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

  16. Treatment of multiple resistant field strain of Ostertagia spp. in Cashmere and Angora goats.

    PubMed

    Várady, M; Praslicka, J; Corba, J

    1994-05-01

    A multiple resistant field strain of gastro-intestinal nematodes was detected in Cashmere and Angora goats imported from New Zealand. Different treatments with three types of broad spectrum anthelmintics (albendazole, levamisole/tetramisole and ivermectin) at various dose rates are described. Satisfactory effect in Angora goats was not achieved until all three anthelmintics were administered simultaneously at twice the normal sheep dose. Post mortem worm counts and identification revealed that the resistant population consisted of 89% Ostertagia circumcincta, 6% Ostertagia ostertagi and 5% Ostertagia trifurcata. However, egg hatch assay carried out seven months later detected the presence of resistant nematodes again.

  17. 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

  18. Murine cytomegalovirus stimulates natural killer cell function but kills genetically resistant mice treated with radioactive strontium

    SciTech Connect

    Masuda, A.; Bennett, M.

    1981-12-01

    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.

  19. 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

  20. Polymerase chain reaction-based screening for the ceftriaxone-resistant Neisseria gonorrhoeae F89 strain.

    PubMed

    Goire, N; Lahra, M M; Ohnishi, M; Hogan, T; Liminios, A E; Nissen, M D; Sloots, T P; Whiley, D M

    2013-04-04

    Emergence and spread of Neisseria gonorrhoeae resistant to extended spectrum cephalosporins is a major problem threatening treatment of gonorrhoea and is further highlighted by the recent report of a second ceftriaxone-resistant N. gonorrhoeae strain (F89) in Europe, initially observed in France and subsequently identified in Spain. N. gonorrhoeae antimicrobial resistance (AMR) surveillance has acquired new importance and molecular tools have the potential to enhance bacterial culture-based methods. In this study, we established a polymerase chain reaction (PCR) protocol for direct detection of the F89 strain. A key component of this screening protocol was the development of a hybridisation probe-based melting curve analysis assay (mosaic501-hybPCR) to detect the presence of an A501P substitution on the N. gonorrhoeae mosaic penicillin binding protein 2 (PBP2) sequence, an important characteristic of the F89 strain. The mosaic501-hybPCR was evaluated using plasmid-derived positive controls (n=3) and characterised gonococcal (n=33) and non-gonococcal (n=58) isolates. The protocol was then applied to 159 clinical specimens from Sydney, Australia, collected during the first half of the year 2012 that were N. gonorrhoeae PCR-positive. Overall, the results indicate that the PCR-based protocol is suitable for direct detection of the N. gonorrhoeae F89 strain in non-cultured clinical samples. It therefore provides an additional tool to aid investigations into the potential spread of F89 strain throughout Europe and elsewhere.

  1. Purification and properties of an esterase from organophosphate-resistant strain of the mosquito Culex quinquefasciatus.

    PubMed Central

    Merryweather, A T; Crampton, J M; Townson, H

    1990-01-01

    Organophosphate-resistant and -susceptible strains of Culex quinquefasciatus (mosquito) have been compared on the basis of their esterase activities. The homozygous resistant strain (Dar) shows two highly active esterases after starch-gel electrophoresis, of Rm 0.2 and 0.4, which are absent from susceptible strains (Apo, Mon), and which previous selection studies have shown to be inseparable from organophosphate resistance. After SDS/polyacrylamide-gel electrophoresis and silver staining of total C. quinquefasciatus proteins, a 62 kDa band is observed in strain Dar at high concentrations, and in susceptible strains in trace amounts. After Western blotting, this 62 kDa protein is recognized by antisera raised against the two esterases eluted from starch gels. After chromatofocusing of Dar proteins, the 62 kDa protein is seen to be associated with esterase activity, and of a similar pI to that observed for esterases after isoelectric focusing. Post-translational modification is not required for recognition of the 62 kDa putative esterase, since the protein is immunoprecipitated by the anti-esterase serum from products of translation of Dar mRNA in vitro. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 6. Fig. 7. PMID:2178604

  2. Complete Genome Sequences of Multidrug-Resistant Campylobacter jejuni Strain 14980A (Turkey Feces) and Campylobacter coli Strain 14983A (Housefly from a Turkey Farm), Harboring a Novel Gentamicin Resistance Mobile Element

    PubMed Central

    Huynh, Steven; Parker, Craig T.; Niedermeyer, Jeffrey A.; Kathariou, Sophia

    2016-01-01

    Multidrug resistance (MDR) in foodborne pathogens is a major food safety and public health issue. Here we describe whole-genome sequences of two MDR strains of Campylobacter jejuni and Campylobacter coli from turkey feces and a housefly from a turkey farm. Both strains harbor a novel chromosomal gentamicin resistance mobile element. PMID:27795285

  3. 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...

  4. 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

  5. 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

  6. 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

  7. Emergence of high level azithromycin-resistant Neisseria gonorrhoeae strain isolated in Argentina.

    PubMed

    Galarza, Patricia G; Alcalá, Belén; Salcedo, Celia; Canigia, Liliana Fernández; Buscemi, Luis; Pagano, Irene; Oviedo, Claudia; Vázquez, Julio A

    2009-12-01

    One Neisseria gonorrhoeae strains highly resistant to azithromycin AzHLR (MIC >2048 mg/L) was isolated in Argentina in 2001 and it has been characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) as ST696, suggesting a different event to other isolates in Europe. Neither, mtrR mutations or presence of mef gene were detected.

  8. 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

  9. 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

  10. 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.

  11. Evidence of Biological Control of Agrobacterium tumefaciens Strains Sensitive and Resistant to Agrocin 84 by Different Agrobacterium radiobacter Strains on Stone Fruit Trees.

    PubMed

    López, M M; Gorris, M T; Salcedo, C I; Montojo, A M; Miró, M

    1989-03-01

    The effectiveness of Agrobacterium radiobacter K84, 0341, and a K84 non-agrocin-producing mutant (K84 Agr) in biological control of crown gall on rootstocks of stone fruit trees was determined in three experiments. In experiment 1, K84 and 0341 controlled crown gall on plum plants in soil inoculated with two strains of Agrobacterium tumefaciens resistant to agrocin 84. In experiment 2, K84 controlled crown gall on peach plants in soils inoculated with strains of A. tumefaciens sensitive or resistant to agrocin 84 or with a mixture of both. However, the effectiveness of K84 was higher against the sensitive strain than against the resistant strain. There was a residual effect of K84 from one year to another in soil inoculated with the sensitive strains. In experiment 3, K84 and K84 Agr controlled crown gall on plum and peach plants in soils inoculated with strains of A. tumefaciens sensitive or resistant to agrocin 84. The control afforded by K84 was higher than that provided by K84 Agr against the sensitive strain but was similar against the resistant strain.

  12. 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.'.

  13. Strain-specific differences in cell proliferation and differentiation in the dentate gyrus of C57BL/6N and C3H/HeN mice fed a high fat diet.

    PubMed

    Hwang, In Koo; Kim, Il Yong; Kim, Dae Won; Yoo, Ki-Yeon; Kim, Yo Na; Yi, Sun Shin; Won, Moo-Ho; Lee, In Se; Yoon, Yeo Sung; Seong, Je Kyung

    2008-11-19

    The authors investigated strain-specific cell proliferation and differentiation differences in the dentate gyri of C57BL/6N (susceptible strain to obesity) and C3H/HeN (resistant strain to obesity) mice. In addition, the influences of a high fat diet (HD) on neuronal differentiation in C57BL/6N and C3H/HeN mice fed a low-fat diet (LD) or HD for 4 or 12 weeks were investigated. Body weight and body weight gains were significantly higher in HD-fed C57BL/6N and C3H/HeN mice than in LD-fed C57BL/6N and C3H/HeN mice. In particular, body weight gains were significantly higher in C57BL/6N mice than in C3H/HeN mice. In both of HD- and LD-fed C57BL/6N and C3H/HeN mice for 4 weeks, some Ki67 and many DCX immunoreactive cells were detected in the subgranular zone of the dentate gyrus. In HD-fed C57BL/6N and C3H/HeN mice, the number of Ki67 immunoreactive cells and DCX immunoreactivities in the dentate gyri were significantly lower than in LD-fed C57BL/6N and C3H/HeN mice. However, the number of Ki67 immunoreactive cells and DCX immunoreactivities in HD-fed C57BL/6N mice were significantly lower than in HD-fed C3H/HeN mice. These results suggest that C57BL/6N mice are more vulnerable to HD induced obesity than C3H/HeN mice. In addition, the feeding of HD was found to exacerbate reduced cell proliferation and differentiation in the dentate gyri of C57BL/6N mice as compared with that in C3H/HeN mice.

  14. [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

  15. First characterization of inhibitor-resistant TEM (IRT) beta-lactamases in Klebsiella pneumoniae strains.

    PubMed Central

    Lemozy, J; Sirot, D; Chanal, C; Huc, C; Labia, R; Dabernat, H; Sirot, J

    1995-01-01

    Two clinical strains of Klebsiella pneumoniae, TP 01 and TP 02, presented resistance to amoxicillin-clavulanate and were fully susceptible to cephalothin. These strains produced two beta-lactamases, SHV-1 and a TEM enzyme with a pI of 5.2. The previously described changes Arg-244-->Cys and Arg-244-->Ser in IRT-1 and IRT-2 (A. Belaaouaj, C. Lapoumeroulie, M. M. Caniça, G. Vedel, P. Nevot, R. Krishnamoorthy, and G. Paul, FEMS Microbiol. Lett. 120:75-80, 1994) were found in TEM enzymes from the TP 01 and TP 02 strains, respectively. This is the first report of inhibitor-resistant TEM (IRT) in species other than Escherichia coli from the family Enterobacteriaceae. PMID:8585751

  16. Sendai virus-induced alterations in lung structure/function correlate with viral loads and reveal a wide resistance/susceptibility spectrum among mouse strains.

    PubMed

    Faisca, Pedro; Anh, Dao Bui Tran; Desmecht, Daniel J-M

    2005-11-01

    The Paramyxoviridae family includes some of the most important and ubiquitous disease-causing viruses of infants and children, most of which cause significant infections of the respiratory tract. Evidence is accumulating in humans that genetic factors are involved in the severity of clinical presentation. As a first step toward the identification of the genes involved, this study was undertaken to establish whether laboratory mouse strains differ in susceptibility to Sendai virus, the murine counterpart of human type-1 parainfluenza virus which, historically, has been used extensively in studies that have defined the basic biological properties of paramyxoviruses in general. With this purpose in mind, double-chamber plethysmography data were collected daily for 7 days after inoculation of Sendai virus in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values closely reflected the success of viral replication in the lungs and revealed a pattern of continuous variation with resistant, intermediate, and susceptible strains. The results unambiguously suggest that BALB/c (resistant) and 129Sv (susceptible) strains should be used in crossing experiments aimed at identifying the genes involved in resistance to Paramyxoviridae by the positional cloning approach.

  17. 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.

  18. 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

  19. Bovine mastitis Staphylococcus aureus: antibiotic susceptibility profile, resistance genes and molecular typing of methicillin-resistant and methicillin-sensitive strains in China.

    PubMed

    Wang, Dengfeng; Wang, Zhicai; Yan, Zuoting; Wu, Jianyong; Ali, Tariq; Li, Jianjun; Lv, Yanli; Han, Bo

    2015-04-01

    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection in dairy animals is of great concern for livestock and public health. The aim of present study was to detect new trends of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) towards antibiotic susceptibility, resistance genes and molecular typing by methods of disc diffusion, multiplex PCR assay and multilocus sequence typing (MLST). A total of 219 S. aureus strains were isolated from bovine mastitis cases from six provinces of China, including 34 MRSA strains. The results revealed that more than 70% isolated strains showed resistance to various antibiotics, and multiple-drugs resistance to more than five categories of antibiotics was found more common. The ermC was the most prevalent resistance gene, followed by other genes; however, ermA was the least frequently detected gene. Twenty-eight mecA-negative MRSA and six mecA-positive MRSA strains were detected, and in which three strains were ST97-MRSA-IV, others were ST965-MRSA-IV, ST6-MRSA-IV and ST9-MRSA-SCCmec-NT. The mecA-negative MRSA strains were found resistant to most of the antibiotics, and harbored aac(6')/aph(2''), aph(3')-III and tetM genes higher than MSSA strains. The resistance to most of the antibiotics was significantly higher in MRSA than in MSSA strains. The MLST profiles showed that these strains mainly belonged to CC5, CC398, CC121 and CC50 lineage, especially within ST97 and ST398, while some novel sequence types (ST2154, ST2165 and ST2166) were identified and deposited in the MLST database. This indicates that the resistance of S. aureus is becoming more complicated by changes in multi-drug resistance mechanism and appearance of mecA-negative MRSA isolates, and importantly, MRSA-IV strains in different MLST types are emerging.

  20. Restricted replication of herpes simplex virus in spinal ganglia of resistant mice is accompanied by an early infiltration of immunoglobulin G-bearing cells.

    PubMed Central

    Cook, M L; Stevens, J G

    1983-01-01

    In an attempt to define the nature of the difference in the susceptibility of C57BL/6 (resistant) and A/J (susceptible) mice to herpes simplex virus type 1, we initiated a study of virus progression through the nervous system. After inoculation of virus in a rear footpad, C57BL/6 mice were found to be more than 500-fold more resistant, but resistance did not extend to pseudorabies virus. In additional investigations, it was found that the virus was selectively restricted at the level of spinal ganglia in C57BL/6 mice. No intrinsic difference in the ability of this tissue from either mouse strain to replicate virus was found. However, by 4 days after infection, morphological investigations indicated that a mononuclear cell infiltrate was present surrounding infected neurons and satellite cells both earlier and in greater numbers in the ganglia of C57BL/6 mice. Immunohistochemical methods showed that most of these cells did not express Thy 1.2 antigen, but the vast majority bore immunoglobulin G. The mechanism by which these infiltrating cells could restrict virus spread is discussed. Images PMID:6302004

  1. Molecular characterization of enterotoxigenic and borderline oxacillin resistant Staphylococcus strains from ovine milk.

    PubMed

    Perillo, Jusy; Ceccarelli, Daniela; Spagnoletti, Matteo; Lollai, Stefano; Cappuccinelli, Piero; Colombo, Mauro M

    2012-12-01

    Staphylococcal enterotoxins (SEs) produced by Staphylococcus spp. are superantigens responsible for food-poisoning and are associated to mobile genetic elements such as Staphylococcus aureus pathogenicity islands (SaPI). The presence of 13 enterotoxin genes (sea, seb, sec, sed, see, seg, seh, sei, sej, sel, sek, seq, and tst) was tested in 15 S. aureus and 24 coagulase-negative Staphylococcus (CNS) multi-resistant strains isolated from ovine milk in Sardinia. All CNS isolates were enterotoxin-negative, whereas co-presence of sec, sel and tst was observed in most of the S. aureus strains. One isolate of S. aureus was characterized by tst alone. A multiplex PCR assay aimed at discriminating between the integrase genes of pathogenicity islands SaPI2, SaPIbov1, and SaPIMW2 was developed. We demonstrated that strains harboring sec, sel and tst were associated with SaPIbov1, whereas the strain positive for tst was associated with SaPI2. Borderline oxacillin resistant S. aureus strains were also detected. RAPD analysis of the Staphylococcus strains showed that clonal relationships were correlated with pathogenic profiles.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. The effect of shearing strain-rate on the ultimate shearing resistance of clay

    NASA Technical Reports Server (NTRS)

    Cheng, R. Y. K.

    1976-01-01

    The shearing resistance of cohesive soils subjected to a high rate of shearing strain was investigated. 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 to date, 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 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.

  8. 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.

  9. 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

  10. 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

  11. Selection and Preliminary Mechanism of Resistance to Profenofos in a Field Strain of Musca domestica (Diptera: Muscidae) from Pakistan.

    PubMed

    Khan, Hafiz Azhar Ali; Akram, Waseem; Iqbal, Naeem

    2015-09-01

    House flies are major insect pests at dairy farms in Pakistan and are mainly controlled with insecticides of different classes, including organophosphates. To develop a better resistance management strategy, a field strain of house flies was selected in the laboratory to study the potential for the development of resistance, possible mechanisms of resistance and cross-resistance to other insecticides. The selection of the field strain with profenofos for five consecutive generations resulted in the LC50 values to increase from 50.49 to 176.03 µg/ml, and the resistance ratio increased from 29.70 to 103.55 as compared with a laboratory-susceptible strain; however, the resistance was decreased significantly when the selected strain was reared for the next five generations without exposure to any insecticide. The profenofos-selected strain (Profen-SEL) showed cross-resistance to chlorpyrifos and deltamethrin but no cross-resistance observed to spinosad. Synergism studies with piperonyl butoxide and S,S,S-tributylphosphorotrithioate indicated that the resistance to profenofos was probably associated with esterase and, possibly, microsomal oxidase activity. Resistance to profenofos in the selected strain suggests that the resistance, owing to instability, could be overcome by switching off profenofos use for few generations in the field or by rotation with different insecticides having different modes of action.

  12. 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.

  13. 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

  14. Isolation and genetic analysis of Chlamydomonas reinhardtii strains resistant to cadmium.

    PubMed Central

    Collard, J M; Matagne, R F

    1990-01-01

    In Chlamydomonas reinhardtii, cadmium induces reduction of growth, reduction of chlorophyll content, and lethality. The toxicity was higher in a cell wall-deficient strain than in the wild type. By growing the cells on agar medium containing cadmium at concentrations inducing high lethality, stable resistant clones were isolated. The resistance was due to a nuclear mutation (cadAR) which probably preexisted in the wild-type cell population, as suggested by the fluctuation test. A double mutant (cadAR cadBR) was selected on media containing higher concentrations of cadmium. The cadBR mutation, which is unlinked to cadAR, determines a resistance intermediate between the CadAR mutant and the wild-type strain. Both cadAR and cadBR mutations are partially dominant. PMID:2389932

  15. Heat resistance of an outbreak strain of Listeria monocytogenes in hot dog batter.

    PubMed

    Mazzotta, A S; Gombas, D E

    2001-03-01

    The heat resistance of a strain of Listeria monocytogenes responsible for a listeriosis outbreak in hot dogs was not higher than the heat resistance of other L. monocytogenes strains when tested in tryptic soy broth and in laboratory-prepared hot dog batter. For the thermal death time experiments, the cells were grown to stationary phase or were starved in phosphate-buffered saline, pH 7, for 6 h at 30 degrees C. Starvation increased the heat resistance of L. monocytogenes in broth but not in hot dog batter. D-values in hot dog batter were higher than in broth. For the hot dog formulation used in this study, cooking the hot dog batter for 30 s at 71.1 degrees C (160 degrees F), or its equivalent using a z-value of 6 degrees C (11 degrees F), would inactivate 5 logs of L. monocytogenes.

  16. Isolation of a high malic and low acetic acid-producing sake yeast Saccharomyces cerevisiae strain screened from respiratory inhibitor 2,4-dinitrophenol (DNP)-resistant strains.

    PubMed

    Kosugi, Shingo; Kiyoshi, Keiji; Oba, Takahiro; Kusumoto, Kenichi; Kadokura, Toshimori; Nakazato, Atsumi; Nakayama, Shunichi

    2014-01-01

    We isolated 2,4-dinitrophenol (DNP)-resistant sake yeast strains by UV mutagenesis. Among the DNP-resistant mutants, we focused on strains exhibiting high malic acid and low acetic acid production. The improved organic acid composition is unlikely to be under the control of enzyme activities related to malic and acetic acid synthesis pathways. Instead, low mitochondrial activity was observed in DNP-resistant mutants, indicating that the excess pyruvic acid generated during glycolysis is not metabolized in the mitochondria but converted to malic acid in the cytosol. In addition, the NADH/NAD(+) ratio of the DNP-resistant strains was higher than that of the parental strain K901. These results suggest that the increased NADH/NAD(+) ratio together with the low mitochondrial activity alter the organic acid composition because malic acid synthesis requires NADH, while acetic acid uses NAD(+).

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Virulence ranking of some Mycobacterium tuberculosis and Mycobacterium bovis strains according to their ability to multiply in the lungs, induce lung pathology, and cause mortality in mice.

    PubMed Central

    Dunn, P L; North, R J

    1995-01-01

    Three virulent strains of Mycobacterium tuberculosis (H37Rv, Erdman, and NYH-27) and two virulent strains of M. bovis (Ravenel and Branch) were compared in terms of their growth rates in the livers and the lungs of mice, their ability to cause lung pathology, and the time taken for them to cause death. In immunocompetent mice, all strains caused an infection that progressed for 20 days or more and then underwent resolution in the liver but not in the lungs. In the lungs, infection persisted and induced progressive pathology. According to host survival time, Ravenel was the most virulent strain, followed, in decreasing order of virulence, by Branch, H37Rv, Erdman, and NYH-27. The much longer survival times of mice infected with M. tuberculosis strains allowed time for lung histopathology to change from a histiocytic alveolitis to a chronic fibroblastic fibrosis that eventually obliterated most of the lung architecture. By contrast, in mice infected with M. bovis strains, the alveolitis that developed during early infection was rapid and expansive enough to cause death before chronic lung pathology became evident. In mice depleted of CD4+ T cells, increased growth of all virulent strains induced necrotic exudative lung lesions that rapidly filled most of the alveolar sacs with inflammatory cells. These mice died much earlier than infected control mice did. Attenuated strains had longer population doubling times in vivo and failed to cause progressive disease or pathology in the lungs or livers of immunocompetent mice. PMID:7642273

  4. Different levels of Fos immunoreactivity after repeated handling and injection stress in two inbred strains of mice.

    PubMed

    Ryabinin, A E; Wang, Y M; Finn, D A

    1999-05-01

    Expression of Fos and Fos-related antigens was immunohistochemically analyzed in DBA/2J and C57BL/6J inbred mice in response to acute or repeated handling and injection stress. Both strains showed a strong induction of Fos and Fos-related antigens in discrete areas of hypothalamus, amygdala, neocortex, septum, and thalamus 2 h after an acute intraperitoneal injection of normal saline. To habituate animals to this procedure, mice were subjected to repeated handling and injections during 2 weeks preceding the experiment. This procedure led to complete habituation of the immediate early gene response to injection stress in stress-responsive brain areas of C57BL/6J mice, such that no significant difference was found between expression of these proteins in brains of saline-injected animals after repeated stress vs. control animals. In contrast, many brain areas of saline-injected DBA/2J mice still showed elevated Fos and Fos-related antigen expression after repeated injections. These results indicate that identical habituation procedures do not necessarily lead to identical levels of gene expression in brains of inbred strains of mice. In turn, they suggest that genetic components for some behavioral and pharmacological traits identified using inbred strains could be related to different rates of habituation to experimental procedures.

  5. 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

  6. A comparison of the effect of mescaline on activity and emotional defaecation in seven strains of mice.

    PubMed

    Lush, I E

    1975-09-01

    1 Mescaline hemi-sulphate (35 mg/kg body weight) was injected intraperitoneally into male mice (Mus musculus) from seven genetically diverse laboratory strains. 2 The effect of mescaline was found by comparison of the emotional defaecation and open field activity of mice after mescaline injection with the performance of the same mice after a subsequent saline (0.9% w/v NaCl solution) control injection. 3 In strains A2G, C3H/He, C57BR/cd, CBA/Cam and F/St, mescaline inhibited emotional defaecation and stimulated open field activity. These effects did not occur in strains 1CFW and Schneider. 4 A positive relationship was found between the degree of emotional defaecation characteristic of each strain in the saline control experiment and the inhibitory effect of mescaline on emotional defaecation. 5 Pre-treatment of mice with tranylcypromine (20 mg/kg body weight, i.p.) had no effect on emotional defaecation or on its inhibition by mescaline.

  7. Transgenic mice with muscle-specific insulin resistance develop increased adiposity, impaired glucose tolerance, and dyslipidemia.

    PubMed

    Moller, D E; Chang, P Y; Yaspelkis, B B; Flier, J S; Wallberg-Henriksson, H; Ivy, J L

    1996-06-01

    Impaired skeletal muscle insulin receptor function is a feature of common forms of insulin resistance, including obesity and noninsulin-dependent diabetes mellitus. However, the extent to which this defect accounts for impaired muscle glucose disposal or altered in vivo glucose homeostasis remains to be established. We recently showed that transgenic mice that overexpress dominant-negative insulin receptors specifically in striated muscle have a severe defect in muscle insulin receptor-mediated signaling and modest hyperinsulinemia. Here we performed hindlimb perfusion studies to determine the impact of this defect on muscle glucose uptake and metabolism. Maximal rates of insulin-stimulated muscle 3-O-methylglucose transport were reduced by 32-40% in transgenic mice with proportional defects involving total hindlimb [14C]glucose uptake, lactate production, and muscle glycogen synthesis. To address the hypothesis that muscle insulin resistance could promote an increase in the accretion of body fat, carcass analysis was performed using two independent lines of transgenic mice. Although body weights were normal, transgenic mice had a 22-38% increase in body fat, with a reciprocal decrease (10-15%) in body protein. Mean gonadal fat pad weight was also increased in transgenic mice. Skeletal muscle histology and fiber type distribution were not affected. To determine whether muscle-specific insulin resistance was sufficient to cause impaired glucose tolerance, oral glucose tolerance tests were performed with 6-month-old transgenic and control mice. Fasting glucose levels were increased by 25%, and peak values were 22-40% higher in transgenic mice. Transgenic mice also had a 37% decrease in plasma lactate levels and modest increases in levels of plasma triglycerides and FFA (29% and 15%, respectively). We conclude that 1) severe defects in muscle insulin receptor function result in impaired insulin-stimulated glucose uptake and metabolism in this tissue; 2) muscle

  8. Antibiotic resistance patterns of coagulase-negative staphylococcus strains isolated from blood cultures of septicemic patients in Turkey.

    PubMed

    Koksal, F; Yasar, H; Samasti, M

    2009-01-01

    The aim of this study is to determine antibiotic resistance patterns and slime production characteristics of coagulase-negative Staphylococci (CoNS) caused nosocomial bacteremia. A total of 200 CoNS strains were isolated from blood samples of patients with true bacteremia who were hospitalized in intensive care units and in other departments of Istanbul University Cerrahpasa Medical Hospital between 1999 and 2006. Among 200 CoNS isolates, Staphylococcus epidermidis was the most prevalent species (87) followed by Staphylococcus haemolyticus (23), Staphylococcus hominis (19), Staphylococcus lugdunensis (18), Staphylococcus capitis (15), Staphylococcus xylosus (10), Staphylococcus warneri (8), Staphylococcus saprophyticus (5), Staphylococcus lentus (5), Staphylococcus simulans (4), Staphylococcus chromogenes (3), Staphylococcus cohnii (1), Staphylococcus schleiferi (1), and Staphylococcus auricularis (1). Resistance to methicillin was detected in 67.5% of CoNS isolates. Methicillin-resistant CoNS strains were determined to be more resistant to antibiotics than methicillin-susceptible CoNS strains. Resistance rates of methicillin-resistant and methicillin-susceptible CoNS strains to the antibacterial agents, respectively, were as follows: gentamicin 90% and 17%, erythromycin 80% and 37%, clindamycin 72% and 18%, trimethoprim-sulfamethoxazole 68% and 38%, ciprofloxacin 67% and 23%, tetracycline 60% and 45%, chloramphenicol 56% and 13% and fusidic acid 25% and 15%. None of the strains were resistant to vancomycin and teicoplanin. Slime production was detected in 86 of 200 CoNS strains. Resistance to methicillin was found in 81% of slime-positive and in 57% of slime-negative strains. Our results indicated that there is a high level of resistance to widely used agents in causative methicillin-resistant CoNS strains. However fusidic acid has the smallest resistance ratio, with the exception of glycopeptides. Additionally, most S. epidermidis strains were slime

  9. Resistance profiles and genetic diversity of Escherichia coli strains isolated from acute bovine mastitis.

    PubMed

    Moser, A; Stephan, R; Corti, S; Lehner, A

    2013-06-01

    Between March 2011 and February 2012 83 E. coli strains were isolated from mastitis milk samples from 83 different animals (67 farms) and tested for their sensitivity to various antibiotics by means of disk diffusion method and genotyped by determination of the phylogenetic groups as well as by pulsed field gel electrophoresis (PFGE). The antibiotics were chosen on the basis of their licenses for intramammary application in Switzerland. As many as 16.9 % of the isolates were resistant to one or more antimicrobial agents. Amoxicillin-clavulanic acid, gentamicin and third generation cephalosporins proved effective against the majority of these strains. Nevertheless, one blaCTX-M-14 harbouring extended-spectrum-beta-lactamase producing strain was found. Genetic analysis grouped most of the strains (87 %) into phylogenetic groups A and B1. PFGE genotyping demonstrated that E. coli from cows with mastitis even from the same farm were genotypically very diverse.

  10. 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

  11. 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.

  12. Establishment of a tamoxifen-inducible Cre-driver mouse strain for widespread and temporal genetic modification in adult mice

    PubMed Central

    Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki

    2016-01-01

    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

  13. satG, Conferring Resistance to Streptogramin A, Is Widely Distributed in Enterococcus faecium Strains but Not in Staphylococci

    PubMed Central

    Haroche, Julien; Allignet, Jeanine; Aubert, Sylvie; Van Den Bogaard, Anthony E.; El Solh, Névine

    2000-01-01

    A gene almost identical to satG was isolated from an Enterococcus faecium strain. This gene was transferred to a Staphylococcus aureus recipient strain where it conferred resistance to streptogramin A. satG was found to be widely distributed among E. faecium strains but not detected among staphylococci. PMID:10602747

  14. Genome Sequence of the Multiple-β-Lactam-Antibiotic-Resistant Bacterium Acidovorax sp. Strain MR-S7.

    PubMed

    Miura, Takamasa; Kusada, Hiroyuki; Kamagata, Yoichi; Hanada, Satoshi; Kimura, Nobutada

    2013-06-27

    Acidovorax sp. strain MR-S7 was isolated from activated sludge in a treatment system for wastewater containing β-lactam antibiotic pollutants. Strain MR-S7 demonstrates multidrug resistance for various types of β-lactam antibiotics at high levels of MIC. The draft genome sequence clarified that strain MR-S7 harbors unique β-lactamase genes.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Resistance of mice vaccinated with rabies virus internal structural proteins to lethal infection.

    PubMed

    Takita-Sonoda, Y; Fujii, H; Mifune, K; Ito, Y; Hiraga, M; Nishizono, A; Mannen, K; Minamoto, N

    1993-01-01

    Mice were vaccinated with recombinant vaccinia virus (rVac) expressing the glycoprotein (G), nucleoprotein (N), phosphoprotein (NS) or matrix protein (M) of rabies virus and their resistance to peripheral lethal infection with street rabies virus was examined. Mice vaccinated with rVac-G or rVac-N developed strong antibody responses to the corresponding proteins and essentially all mice survived challenge infection. Mice vaccinated with rVac-NS or rVac-M developed only a slight antibody response, however, a significant protection (59%) was observed in the rVac-NS-vaccinated mice, whereas rVac-M-vaccinated mice were not protected. No anti-G antibodies were detected in the sera of mice which has been vaccinated with rVac-N or rVac-NS and survived challenge infection. Passive transfer of anti-N monoclonal antibodies (MAbs) recognizing an epitope located on amino acids 1-224 of the protein prior to challenge resulted in significant protection, although the protection was not complete even with a high amount of antibodies. In contrast, none of the mice given MAbs recognizing an epitope of amino acids 247-415 or F(ab')2 fragments from a protective MAb IgG were protected. Administration of anti-CD 8 MAb to rVac-N-vaccinated mice showed no significant effect on protection. Our observations suggest that a considerable part of the protection achieved by the vaccination with rVac-N can be ascribed to the intact anti-N antibodies recognizing an epitope located on amino acids 1-224 of the protein.

  20. 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

  1. 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.

  2. Antibiotic resistance patterns and PCR-ribotyping of Clostridium difficile strains isolated from swine and dogs in Italy.

    PubMed

    Spigaglia, Patrizia; Drigo, Ilenia; Barbanti, Fabrizio; Mastrantonio, Paola; Bano, Luca; Bacchin, Cosetta; Puiatti, Cinzia; Tonon, Elena; Berto, Giacomo; Agnoletti, Fabrizio

    2015-02-01

    Recent studies suggest animals, in particular farm and companion animals, as possible reservoir for Clostridium difficile human pathogenic strains. The aim of this study was to give a first characterization of C. difficile isolates from Italian swine and dogs. In total, 10 different PCR-ribotypes were identified among porcine strains and six among canine strains. The predominant type found among porcine strains was 078 (50%), whereas the most frequently detected among canine strains was the non-toxinogenic 010 (64%). Considering the CLSI breakpoints, 60% of porcine isolates was resistant to ERY, 35% to MXF, 15% to CLI, 5% to RIF, and none to MTZ or VAN. Among dogs, 51% of strains was resistant to CLI, 46% to ERY, 21% to MTZ and 5% to MXF or RIF, and none to VAN. Five porcine strains (10%) and 9 canine isolates (41%) were MDR. Interestingly, 8 MDR canine strains were highly resistant to MTZ, with MICs ≥32 mg/L. Considering the EUCAST cut-off for MTZ (MIC >2 mg/L), 13 canine isolates and one porcine strain were found with reduced susceptibility to MTZ (MICs ranging from 3 to ≥256 mg/L). Swine and canine strains showing resistance or reduced susceptibility to MTZ belonged to PCR-ribotype 010 and 078. These PCR-ribotypes have been associated to reduced susceptibility to MTZ also in human, suggesting a potential risk for the emergence of C. difficile strains resistant to the current first-line antibiotic for CDI treatment. The agar incorporation method (AIM) was confirmed as the best method to detect C. difficile strains with this phenotype also after strains manipulations. The results obtained add further evidences about the possible role of animals as source of MDR C. difficile strains and reservoir of antibiotic resistance determinants.

  3. Alteration of JNK-1 Signaling in Skeletal Muscle Fails to Affect Glucose Homeostasis and Obesity-Associated Insulin Resistance in Mice

    PubMed Central

    Spohn, Gabriele; Brönneke, Hella S.; Schmidt-Supprian, Marc; Wunderlich, F. Thomas

    2013-01-01

    Obesity and associated metabolic disturbances, such as increased circulating fatty acids cause prolonged low grade activation of inflammatory signaling pathways in liver, skeletal muscle, adipose tissue and even in the CNS. Activation of inflammatory pathways in turn impairs insulin signaling, ultimately leading to obesity-associated type 2 diabetes mellitus. Conventional JNK-1 knock out mice are protected from high fat diet-induced insulin resistance, characterizing JNK-1-inhibition as a potential approach to improve glucose metabolism in obese patients. However, the cell type-specific role of elevated JNK-1 signaling as present during the course of obesity has not been fully elucidated yet. To investigate the functional contribution of altered JNK-1 activation in skeletal muscle, we have generated a ROSA26 insertion mouse strain allowing for Cre-activatable expression of a JNK-1 constitutive active construct (JNKC). To examine the consequence of skeletal muscle-restricted JNK-1 overactivation in the development of insulin resistance and glucose metabolism, JNKC mice were crossed to Mck-Cre mice yielding JNKSM-C mice. However, despite increased muscle-specific JNK activation, energy homeostasis and glucose metabolism in JNKSM-C mice remained largely unaltered compared to controls. In line with these findings, obese mice with skeletal muscle specific disruption of JNK-1, did not affect energy and glucose homeostasis. These experiments indicate that JNK-1 activation in skeletal muscle does not account for the major effects on diet-induced, JNK-1-mediated deterioration of insulin action and points towards a so far underappreciated role of JNK-1 in other tissues than skeletal muscle during the development of obesity-associated insulin resistance. PMID:23349837

  4. Different patterns of expression and of IL-10 modulation of inflammatory mediators from macrophages of Lyme disease-resistant and -susceptible mice.

    PubMed

    Gautam, Aarti; Dixit, Saurabh; Embers, Monica; Gautam, Rajeev; Philipp, Mario T; Singh, Shree R; Morici, Lisa; Dennis, Vida A

    2012-01-01

    C57BL/6J (C57) mice develop mild arthritis (Lyme disease-resistant) whereas C3H/HeN (C3H) mice develop severe arthritis (Lyme disease-susceptible) after infection with the spirochete Borrelia burgdorferi. We hypothesized that susceptibility and resistance to Lyme disease, as modeled in mice, is associated with early induction and regulation of inflammatory mediators by innate immune cells after their exposure to live B. burgdorferi spirochetes. Here, we employed multiplex ELISA and qRT-PCR to investigate quantitative differences in the levels of cytokines and chemokines produced by bone marrow-derived macrophages from C57 and C3H mice after these cells were exposed ex vivo to live spirochetes or spirochetal lipoprotein. Upon stimulation, the production of both cytokines and chemokines was up-regulated in macrophages from both mouse strains. Interestingly, however, our results uncovered two distinct patterns of spirochete- and lipoprotein-inducible inflammatory mediators displayed by mouse macrophages, such that the magnitude of the chemokine up-regulation was larger in C57 cells than it was in C3H cells, for most chemokines. Conversely, cytokine up-regulation was more intense in C3H cells. Gene transcript analyses showed that the displayed patterns of inflammatory mediators were associated with a TLR2/TLR1 transcript imbalance: C3H macrophages expressed higher TLR2 transcript levels as compared to those expressed by C57 macrophages. Exogenous IL-10 dampened production of inflammatory mediators, especially those elicited by lipoprotein stimulation. Neutralization of endogenously produced IL-10 increased production of inflammatory mediators, notably by macrophages of C57 mice, which also displayed more IL-10 than C3H macrophages. The distinct patterns of pro-inflammatory mediator production, along with TLR2/TLR1 expression, and regulation in macrophages from Lyme disease-resistant and -susceptible mice suggests itself as a blueprint to further investigate

  5. The persistence of drug resistant Escherichia coli strains in the majority faecal flora of calves.

    PubMed Central

    Hinton, M.; Rixson, P. D.; Allen, V.; Linton, A. H.

    1984-01-01

    Two groups of calves, one of three and the other of two animals, were purchased in markets and reared initially on a commercial veal unit for 1 month and 4 months respectively. They were then moved to the Veterinary School, Langford, and kept for a further 6 and 4 months respectively. The animals were sampled weekly and a continual turnover in the strains forming the majority Escherichia coli faecal flora was demonstrated for all calves. Antibacterial-drug resistance, as measured by an Antibiotic Resistance Index (ARI), increased after arrival on the veal unit and persisted at high levels during the whole of their stay. After moving to Langford the ARI fell. Initially there was a reduction in the average number of resistance determinants per resistant strain and then, after a delay of up to 8 weeks, by an increase in the proportion of isolates that were fully sensitive. The source of the sensitive strains was not ascertained, although their appearance was not associated specifically with either weaning or turning out to pasture. PMID:6392420

  6. 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.

  7. High affinity InhA inhibitors with activity against drug-resistant strains of Mycobacterium tuberculosis.

    PubMed

    Sullivan, Todd J; Truglio, James J; Boyne, Melissa E; Novichenok, Polina; Zhang, Xujie; Stratton, Christopher F; Li, Huei-Jiun; Kaur, Tejinder; Amin, Amol; Johnson, Francis; Slayden, Richard A; Kisker, Caroline; Tonge, Peter J

    2006-02-17

    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' value of 1 nM for InhA and MIC99 values of 2-3 microg mL(-1) (6-10 microM) for both drug-sensitive and drug-resistant strains of MTB. Overexpression of InhA in MTB results in a 9-12-fold increase in MIC99, 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.

  8. 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

  9. Prevalence of Antimicrobial Resistance in Escherichia coli Strains Isolated from Fishery Workers

    PubMed Central

    Shin, Hyun-Ho; Cho, Seung-Hak

    2013-01-01

    Objectives: This study aimed to characterize the prevalence of antibiotic resistance in Escherichia coli isolates from the fecal samples of fishery workers who work in fish farms and often use antibiotics for the feeding fishes. Methods: Seventy-three E. coli strains isolated from the fecal samples of fishery workers and 180 isolates from a control group of restaurant workers were tested for antibiotic resistance by agar disk diffusion with 16 antimicrobial agents. Results: About 30% of isolates from each group showed antimicrobial resistance to ampicillin, and 60% of isolates from fishery workers and 41% from restaurant workers were resistant to tetracycline. The isolates showed higher resistance to cephalothin and cefoxitin than to other cephem antibiotics and to gentamicin than to other aminogycosides. Our data indicated that fecal E. coli isolates from fishery workers showed higher antibiotic resistance than those of non-fishery workers (restaurant workers), especially to cephalothin, tetracycline, and trimethoprim–sulfamethoxazole (p < 0.05). However, rates of multidrug resistance were similar among the fishery workers and restaurant workers. Conclusion: Frequent use of antibiotics may cause increased antibiotic resistance in the human microbiome. PMID:24159534

  10. 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.

  11. 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

  12. Chitotriosidase activity in the blood serum and organs of mice of various strains under the influence of chitin.

    PubMed

    Monoszon, A A; Cherkanova, M S; Duzhak, A B; Korolenko, T A

    2012-11-01

    Mouse chitotriosidase cleaving chitin belongs to the family of mammalian chitinases, whose biological functions are poorly understood. Chitotriosidase activity in mouse serum was shown to be much higher than in humans. The following interstrain differences were revealed in mouse chitotriosidase activity: GR>C57Bl/6>BALB/c>A/Sn>CBA. Chitotriosidase activity in CBA mice was lowest and practically did not differ from that in C3H/He and ICR mice. No sex-related differences were found in enzyme activity. Hybrids of opposite strains CBA and C57Bl/6 were characterized by dominant inheritance of this sign (elevated activity of chitotriosidase in the serum). Intragastric administration of chitin in a single dose of 100 mg/kg was followed by a decrease in chitotriosidase activity in the lungs, but not in the blood serum and homogenate of gastric cells from CBA mice. These data indicate that intragastric administration of chitin does not induce chitotriosidase in mice.