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  • American Society for Microbiology  (17)
  • English  (17)
  • 2015-2019  (17)
  • 1
    Online Resource
    Online Resource
    Carbon Fixation Driven by Molecular Hydrogen Results in Chemolithoautotrophically Enhanced Growth of Helicobacter pylori
    American Society for Microbiology ; 2016
    In:  Journal of Bacteriology Vol. 198, No. 9 ( 2016-05), p. 1423-1428
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 198, No. 9 ( 2016-05), p. 1423-1428
    Abstract: A molecular hydrogen (H 2 )-stimulated, chemolithoautotrophic growth mode for the gastric pathogen Helicobacter pylori is reported. In a culture medium containing peptides and amino acids, H 2 -supplied cells consistently achieved 40 to 60% greater growth yield in 16 h and accumulated 3-fold more carbon from [ 14 C]bicarbonate (on a per cell basis) in a 10-h period than cells without H 2 . Global proteomic comparisons of cells supplied with different atmospheric conditions revealed that addition of H 2 led to increased amounts of hydrogenase and the biotin carboxylase subunit of acetyl coenzyme A (acetyl-CoA) carboxylase (ACC), as well as other proteins involved in various cellular functions, including amino acid metabolism, heme synthesis, or protein degradation. In agreement with this result, H 2 -supplied cells contained 3-fold more ACC activity than cells without H 2 . Other possible carbon dioxide (CO 2 ) fixation enzymes were not up-expressed under the H 2 -containing atmosphere. As the gastric mucus is limited in carbon and energy sources and the bacterium lacks mucinase, this new growth mode may contribute to the persistence of the pathogen in vivo . This is the first time that chemolithoautotrophic growth is described for a pathogen. IMPORTANCE Many pathogens must survive within host areas that are poorly supplied with carbon and energy sources, and the gastric pathogen Helicobacter pylori resides almost exclusively in the nutritionally stringent mucus barrier of its host. Although this bacterium is already known to be highly adaptable to gastric niches, a new aspect of its metabolic flexibility, whereby molecular hydrogen use (energy) is coupled to carbon dioxide fixation (carbon acquisition) via a described carbon fixation enzyme, is shown here. This growth mode, which supplements heterotrophy, is termed chemolithoautotrophy and has not been previously reported for a pathogen.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.00041-16
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131
    American Society for Microbiology ; 2016
    In:  mBio Vol. 7, No. 2 ( 2016-05-04)
    Details
    In: mBio, American Society for Microbiology, Vol. 7, No. 2 ( 2016-05-04)
    Abstract: Escherichia coli , perennially a major bacterial pathogen, is becoming increasingly difficult to manage due to emerging resistance to all preferred antimicrobials. Resistance is concentrated within specific E. coli lineages, such as sequence type 131 (ST131). Clarification of the genetic basis for clonally associated resistance is key to devising intervention strategies. We used high-resolution genomic analysis of a large global collection of ST131 isolates to define the evolutionary history of extended-spectrum beta-lactamase production in ST131. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance elements. Both global distribution and regional segregation were evident. The diversity of resistance element acquisition and propagation within ST131 indicates a need for control and surveillance strategies that target both bacterial strains and mobile genetic elements.
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    URL: Article
    DOI: 10.1128/mBio.02162-15
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
    detail.hit.zdb_id: 2557172-2
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  • 3
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    Race/Ethnicity and Protease Inhibitor Use Influence Plasma Tenofovir Exposure in Adults Living with HIV-1 in AIDS Clinical Trials Group Study A5202
    American Society for Microbiology ; 2019
    In:  Antimicrobial Agents and Chemotherapy Vol. 63, No. 4 ( 2019-04)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 63, No. 4 ( 2019-04)
    Abstract: AIDS Clinical Trial Group study A5202 (ClinicalTrials.gov identifier NCT00118898) was a phase 3b, randomized, partially blinded equivalence study of open-label atazanavir/ritonavir or efavirenz, plus either placebo-controlled tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, in treatment-naive adults living with HIV-1, evaluating efficacy, safety, and tolerability. We report an analysis of the contribution of participant characteristics to the disposition of tenofovir plasma concentrations. Tenofovir concentration data from a total of 817 individuals (88% of the total number of eligible patients randomly assigned to receive treatment in the TDF-containing arms of A5202) were available for analysis. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. One- and two-compartment models with first-order absorption and first-order elimination were evaluated. An exponential error model was used for examination of interindividual variability (IIV), and a proportional and mixed-error model was assessed for residual variability. The final structural model contained two compartments with first-order absorption and elimination. IIV was estimated for apparent clearance (CL/F) and the first-order absorption rate constant ( k a ), and a proportional residual variability model was selected. The final mean parameter estimates were as follows: k a = 2.87 h −1 , CL/F = 37.2 liters/h, apparent volumes of the central and peripheral compartments = 127 and 646 liters, respectively, and apparent intercompartmental clearance = 107 liters/h. In addition to race/ethnicity, creatinine clearance and assignment to atazanavir/ritonavir or efavirenz were significantly associated with CL/F ( P 〈 0.001). In conclusion, race/ethnicity is associated with tenofovir oral CL in HIV-1 positive, treatment-naive adults. This covariate relationship raises questions about the possibility of differences in efficacy and risk of adverse events in different patient populations and suggests that examining preexposure prophylaxis regimens and tenofovir exposure in different race/ethnicity groups be considered.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01638-18
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 4
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    Online Resource
    Preclinical Characterization and In Vivo Efficacy of GSK8853, a Small-Molecule Inhibitor of the Hepatitis C Virus NS4B Protein
    American Society for Microbiology ; 2015
    In:  Antimicrobial Agents and Chemotherapy Vol. 59, No. 10 ( 2015-10), p. 6539-6550
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 59, No. 10 ( 2015-10), p. 6539-6550
    Abstract: The hepatitis C virus (HCV) NS4B protein is an antiviral therapeutic target for which small-molecule inhibitors have not been shown to exhibit in vivo efficacy. We describe here the in vitro and in vivo antiviral activity of GSK8853, an imidazo[1,2- a ]pyrimidine inhibitor that binds NS4B protein. GSK8853 was active against multiple HCV genotypes and developed in vitro resistance mutations in both genotype 1a and genotype 1b replicons localized to the region of NS4B encoding amino acids 94 to 105. A 20-day in vitro treatment of replicons with GSK8853 resulted in a 2-log drop in replicon RNA levels, with no resistance mutation breakthrough. Chimeric replicons containing NS4B sequences matching known virus isolates showed similar responses to a compound with genotype 1a sequences but altered efficacy with genotype 1b sequences, likely corresponding to the presence of known resistance polymorphs in those isolates. In vivo efficacy was tested in a humanized-mouse model of HCV infection, and the results showed a 3-log drop in viral RNA loads over a 7-day period. Analysis of the virus remaining at the end of in vivo treatment revealed resistance mutations encoding amino acid changes that had not been identified by in vitro studies, including NS4B N56I and N99H. Our findings provide an in vivo proof of concept for HCV inhibitors targeting NS4B and demonstrate both the promise and potential pitfalls of developing NS4B inhibitors.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00813-15
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 5
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    Online Resource
    Borrelia burgdorferi RevA Significantly Affects Pathogenicity and Host Response in the Mouse Model of Lyme Disease
    American Society for Microbiology ; 2015
    In:  Infection and Immunity Vol. 83, No. 9 ( 2015-09), p. 3675-3683
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 83, No. 9 ( 2015-09), p. 3675-3683
    Abstract: The Lyme disease spirochete, Borrelia burgdorferi , expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, with increased fibrotic collagen deposition in tibiotarsal joints. The mutants also induced increased levels of the chemokine CCL2, a monocyte chemoattractant, in serum, and this increase was abolished in the complemented strain. Therefore, while revA is not absolutely essential for infection, deletion of revA had distinct effects on dissemination, arthritis severity, and host response.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.00530-15
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
    detail.hit.zdb_id: 1483247-1
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  • 6
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    The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence
    American Society for Microbiology ; 2015
    In:  Antimicrobial Agents and Chemotherapy Vol. 59, No. 8 ( 2015-08), p. 4436-4445
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 59, No. 8 ( 2015-08), p. 4436-4445
    Abstract: Mycobacterium tuberculosis must sense and adapt to host environmental cues to establish and maintain an infection. The two-component regulatory system PhoPR plays a central role in sensing and responding to acidic pH within the macrophage and is required for M. tuberculosis intracellular replication and growth in vivo . Therefore, the isolation of compounds that inhibit PhoPR-dependent adaptation may identify new antivirulence therapies to treat tuberculosis. Here, we report that the carbonic anhydrase inhibitor ethoxzolamide inhibits the PhoPR regulon and reduces pathogen virulence. We show that treatment of M. tuberculosis with ethoxzolamide recapitulates phoPR mutant phenotypes, including downregulation of the core PhoPR regulon, altered accumulation of virulence-associated lipids, and inhibition of Esx-1 protein secretion. Quantitative single-cell imaging of a PhoPR-dependent fluorescent reporter strain demonstrates that ethoxzolamide inhibits PhoPR-regulated genes in infected macrophages and mouse lungs. Moreover, ethoxzolamide reduces M. tuberculosis growth in both macrophages and infected mice. Ethoxzolamide inhibits M. tuberculosis carbonic anhydrase activity, supporting a previously unrecognized link between carbonic anhydrase activity and PhoPR signaling. We propose that ethoxzolamide may be pursued as a new class of antivirulence therapy that functions by modulating expression of the PhoPR regulon and Esx-1-dependent virulence.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00719-15
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 7
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    Patient-to-Patient Transmission of Acinetobacter baumannii Gastrointestinal Colonization in the Intensive Care Unit
    American Society for Microbiology ; 2019
    In:  Antimicrobial Agents and Chemotherapy Vol. 63, No. 8 ( 2019-08)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 63, No. 8 ( 2019-08)
    Abstract: Acinetobacter baumannii is an important nosocomial pathogen. The objective of this study was to determine the proportion of A. baumannii infections due to patient-to-patient transmission by analyzing the molecular epidemiology of patients who acquired A. baumannii , using perianal surveillance cultures in a large 2-year intensive care unit (ICU) population. The design was a prospective cohort study. Patients who were admitted to the medical and surgical intensive care units at the University of Maryland Medical Center from 2011 to 2013 underwent admission, weekly, and discharge perianal culture collection. Using multilocus sequence typing (MLST) with subsequent pulsed-field gel electrophoresis (PFGE) for increased discrimination, combined with hospital overlap, the number of patients that acquired A. baumannii due to patient-to-patient transmission was determined. Our cohort consisted of 3,452 patients. In total, 196 cohort patients were colonized with A. baumannii ; 130 patients were positive at ICU admission, and 66 patients acquired A. baumannii during their stay. Among the 196 A. baumannii patient isolates, there were 91 unique MLST types. Among the 66 patients who acquired A. baumannii , 31 (50%) were considered genetically related by MLST and/or PFGE type, and 11 (17%) were considered patient-to-patient transmission by genetic relatedness and overlapping hospital stay. Our data show that, of those cases of A. baumannii acquisition, at least 17% were cases of patient-to-patient transmission.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00392-19
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 8
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    Comparison of Three Different FDA-Approved Plasma HIV-1 RNA Assay Platforms Confirms the Virologic Failure Endpoint of 200 Copies per Milliliter Despite Improved Assay Sensitivity
    American Society for Microbiology ; 2015
    In:  Journal of Clinical Microbiology Vol. 53, No. 8 ( 2015-08), p. 2659-2666
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 53, No. 8 ( 2015-08), p. 2659-2666
    Abstract: Discrepancies between HIV-1 RNA results assayed by different FDA-approved platforms have been reported. Plasma samples collected from 332 randomly selected clinical trial participants during the second year of antiretroviral treatment were assayed with three FDA-approved platforms: UltraSensitive Roche Amplicor Monitor, v1.5 (Monitor), the Abbott RealTime HIV-1 test on the m2000 system (Abbott), and the Roche TaqMan HIV-1 test, v2.0 (TaqMan). Samples from 61 additional participants with confirmed HIV-1 RNA levels of 〉 50 copies/ml during trial follow-up were also included. Endpoints were HIV-1 RNA quantification of ≤50 copies/ml versus 〉 50 copies/ml at an individual-sample level (primary) and determination of confirmed virologic failure (VF) from longitudinal samples. A total of 389 participants had results obtained from all assays on at least one sample (median = 6). Proportions of results of 〉 50 copies/ml were 19% (Monitor), 22% (TaqMan), and 25% (Abbott). Despite indication of strong agreement (Cohen's kappa, 0.76 to 0.82), Abbott was more likely to detect HIV-1 RNA levels of 〉 50 copies/ml than Monitor (matched-pair odds ratio [mOR] = 4.2; modified Obuchowski P 〈 0.001) and TaqMan (mOR = 2.1; P 〈 0.001); TaqMan was more likely than Monitor (mOR = 2.6; P 〈 0.001). Despite strong agreement in classifying VF across assay comparisons (kappa, 0.75 to 0.92), at a 50-copies/ml threshold, differences in the probability of VF classification (in the same direction as primary) were apparent (all McNemar's P 〈 0.007). At a 200-copies/ml VF threshold, no differences between assays were apparent (all P 〉 0.13). Despite strong agreement among assays, significant differences were observed with respect to detecting HIV-1 RNA levels of 〉 50 copies/ml and identifying VF at the 50-copies/ml threshold. This has important implications for the definition of VF in clinical trials and clinical practice.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.00801-15
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 9
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    Correction for Johnson et al., Complete Genome Sequences for 59 Burkholderia Isolates, Both Pathogenic and Near Neighbor
    American Society for Microbiology ; 2016
    In:  Genome Announcements Vol. 4, No. 2 ( 2016-04-28)
    Details
    In: Genome Announcements, American Society for Microbiology, Vol. 4, No. 2 ( 2016-04-28)
    Type of Medium: Online Resource
    ISSN: 2169-8287
    URL: Article
    DOI: 10.1128/genomeA.00313-16
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
    detail.hit.zdb_id: 2968655-6
    detail.hit.zdb_id: 2704277-7
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  • 10
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    Comparison of the Microbiota of Older Adults Living in Nursing Homes and the Community
    American Society for Microbiology ; 2017
    In:  mSphere Vol. 2, No. 5 ( 2017-10-25)
    Details
    In: mSphere, American Society for Microbiology, Vol. 2, No. 5 ( 2017-10-25)
    Abstract: Our objective for this study was to characterize the microbial communities of the anterior nares (nose), posterior pharynx (throat), and skin of the femoral and subclavian areas in older adults from nursing homes and the community. Older adults (≥65 years) without antibiotic use for the past 3 months were recruited from nursing homes (NH; n = 16) and from the community (CB; n = 51). Specimens were taken from nose, throat, and skin sites for culture and bacterial profiling using 16S rRNA gene sequencing. We found that pathogenic Gram-negative rod (GNR) colonization on the femoral skin was higher in NH participants than CB participants; otherwise, there were no differences in GNR colonization at other body sites or in Staphylococcus aureus colonization at any body site. Bacterial community profiling demonstrated that the operational taxonomic unit compositions of the different body sites were similar between NH and CB participants, but the analysis identified differences in relative abundance levels. Streptococcus spp. were more abundant and Prevotella spp. were less abundant in the throats of NH participants than in throats of CB participants. Proteus , Escherichia coli , and Enterococcus were more abundant in NH participants on the femoral skin. We found a pattern of decreased abundance of specific Proteobacteria in NH participants at the anterior nares and at both skin sites. We concluded that bacterial communities were largely similar in diversity and composition within body sites between older adults without recent antibiotic use from NH compared to those from the community. Our findings support the rationale for improved hygiene in NH residents to reduce the transmission risk of antibiotic-resistant bacteria, such as Enterococcus spp. or Enterobacteriaceae . IMPORTANCE The nose, throat, and skin over the subclavian and femoral veins are the body sites which harbor the bacteria which most commonly cause health care-associated infection. We assessed the effect of nursing home residence on the microbiota of these body sites in older adults. We found that the microbiota composition of the different body sites was similar between nursing home and community participants, but we identified differences in relative abundance levels. We found remarkable similarities in the bacterial communities of different body sites in older adults who lived in nursing homes compared to those in the community among people who had not been on antibiotics for the past 3 months. We also found that the femoral skin microbiota had evidence of stool contamination in the nursing home residents, providing a rationale for improved skin hygiene. Taken together, it appears that the health care environment does not alter the microbiota to the extent that antibiotics do.
    Type of Medium: Online Resource
    ISSN: 2379-5042
    URL: Article
    DOI: 10.1128/mSphere.00210-17
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2017
    detail.hit.zdb_id: 2844248-9
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