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dc.contributor.authorSingh, Vineet K.
dc.contributor.authorVaish, Manisha
dc.contributor.authorJohansson, Trintje R.
dc.contributor.authorBaum, Kyle R.
dc.contributor.authorRing, Robert P.
dc.contributor.authorSingh, Saumya
dc.contributor.authorShukla, Sanjay K.
dc.contributor.authorMoskovitz, Jackob
dc.date.accessioned2015-03-03T22:01:40Z
dc.date.available2015-03-03T22:01:40Z
dc.date.issued2015-02-13
dc.identifier.citationSingh VK, Vaish M, Johansson TR, Baum KR, Ring RP, et al. (2015) Significance of Four Methionine Sulfoxide Reductases in Staphylococcus aureus. PLoS ONE 10(2): e0117594.

http://dx.doi.org/10.1371/journal.pone.0117594
en_US
dc.identifier.urihttp://hdl.handle.net/1808/16957
dc.description.abstractStaphylococcus aureus is a major human pathogen and emergence of antibiotic resistance in clinical staphylococcal isolates raises concerns about our ability to control these infections. Cell wall-active antibiotics cause elevated synthesis of methionine sulfoxide reductases (Msrs: MsrA1 and MsrB) in S. aureus. MsrA and MsrB enzymes reduce S-epimers and R-epimers of methionine sulfoxide, respectively, that are generated under oxidative stress. In the S. aureus chromosome, there are three msrA genes (msrA1, msrA2 and msrA3) and one msrB gene. To understand the precise physiological roles of Msr proteins in S. aureus, mutations in msrA1, msrA2 and msrA3 and msrB genes were created by site-directed mutagenesis. These mutants were combined to create a triple msrA (msrA1, msrA2 and msrA3) and a quadruple msrAB (msrA1, msrA2, msrA3, msrB) mutant. These mutants were used to determine the roles of Msr proteins in staphylococcal growth, antibiotic resistance, adherence to human lung epithelial cells, pigment production, and survival in mice relative to the wild-type strains. MsrA1-deficient strains were sensitive to oxidative stress conditions, less pigmented and less adherent to human lung epithelial cells, and showed reduced survival in mouse tissues. In contrast, MsrB-deficient strains were resistant to oxidants and were highly pigmented. Lack of MsrA2 and MsrA3 caused no apparent growth defect in S. aureus. In complementation experiments with the triple and quadruple mutants, it was MsrA1 and not MsrB that was determined to be critical for adherence and phagocytic resistance of S. aureus. Overall, the data suggests that MsrA1 may be an important virulence factor and MsrB probably plays a balancing act to counter the effect of MsrA1 in S. aureus.en_US
dc.description.sponsorshipThis work was supported in part by a Warner/Fermaturo grant and A.T. Still University Board of Trustees Research Funds, by grant 1R15AI090680-01 from the National Institutes of Health to VKS, and grants from the Kirksville College of Osteopathic Medicine Biomedical Sciences Graduate Program to TRJ and KRB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.publisherPublic Library of Scienceen_US
dc.rights© 2015 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectStaphylococcus aureusen_US
dc.subjectOcidative stressen_US
dc.subjectMutationen_US
dc.subjectAntibioticsen_US
dc.subjectBacterial geneticsen_US
dc.subjectMethicilin-resistanten_US
dc.subjectMethionineen_US
dc.subjectBacterial pathogensen_US
dc.titleSignificance of Four Methionine Sulfoxide Reductases in Staphylococcus aureusen_US
dc.typeArticle
kusw.kuauthorMoskovitz, Jackob
kusw.kudepartmentDepartment of Pharmacology and Toxicologyen_US
dc.identifier.doi10.1371/journal.pone.0117594
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item meets KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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© 2015 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Except where otherwise noted, this item's license is described as: © 2015 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited