Whole Genome Characterization of the Mechanisms of Daptomycin Resistance in Clinical and Laboratory Derived Isolates of Staphylococcus aureus

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Whole Genome Characterization of the Mechanisms of Daptomycin Resistance in Clinical and Laboratory Derived Isolates of Staphylococcus aureus

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dc.contributor.author Peleg, Anton Y.
dc.contributor.author Miyakis, Spiros
dc.contributor.author Ward, Doyle V.
dc.contributor.author Earl, Ashlee M.
dc.contributor.author Rubio, Aileen
dc.contributor.author Pillai, Satish
dc.contributor.author Cameron, David R.
dc.contributor.author Eliopoulos, George Miltiades
dc.contributor.author Moellering, Robert Charles
dc.date.accessioned 2012-05-08T21:17:44Z
dc.date.issued 2012
dc.identifier.citation Peleg, Anton Y., Spiros Miyakis, Doyle V. Ward, Ashlee M. Earl, Aileen Rubio, David R. Cameron, Satish Pillai, Robert C. Moellering, and George M. Eliopoulos. 2012. Whole genome characterization of the mechanisms of daptomycin resistance in clinical and laboratory derived isolates of staphylococcus aureus. PLoS ONE 7(1): e28316. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8699138
dc.description.abstract Background: Daptomycin remains one of our last-line anti-staphylococcal agents. This study aims to characterize the genetic evolution to daptomycin resistance in S. aureus. Methods: Whole genome sequencing was performed on a unique collection of isogenic, clinical (21 strains) and laboratory (12 strains) derived strains that had been exposed to daptomycin and developed daptomycin-nonsusceptibility. Electron microscopy (EM) and lipid membrane studies were performed on selected isolates. Results: On average, six coding region mutations were observed across the genome in the clinical daptomycin exposed strains, whereas only two mutations on average were seen in the laboratory exposed pairs. All daptomycin-nonsusceptible strains had a mutation in a phospholipid biosynthesis gene. This included mutations in the previously described mprF gene, but also in other phospholipid biosynthesis genes, including cardiolipin synthase (cls2) and CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase (pgsA). EM and lipid membrane composition analyses on two clinical pairs showed that the daptomycin-nonsusceptible strains had a thicker cell wall and an increase in membrane lysyl-phosphatidylglycerol. Conclusion: Point mutations in genes coding for membrane phospholipids are associated with the development of reduced susceptibility to daptomycin in S. aureus. Mutations in cls2 and pgsA appear to be new genetic mechanisms affecting daptomycin susceptibility in S. aureus. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0028316 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253072/pdf/ en_US
dash.license LAA
dc.title Whole Genome Characterization of the Mechanisms of Daptomycin Resistance in Clinical and Laboratory Derived Isolates of Staphylococcus aureus en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Eliopoulos, George Miltiades
dc.date.available 2012-05-08T21:17:44Z

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