Daptomycin resistance in enterococci Is associated with distinct alterations of cell membrane phospholipid content

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dc.contributor.authorMishra, Nagendra N.
dc.contributor.authorBayer, Arnold S.
dc.contributor.authorTran, Truc T.
dc.contributor.authorShamoo, Yousif
dc.contributor.authorMileykovskaya, Eugenia
dc.contributor.authorDowhan, William
dc.contributor.authorGuan, Ziqiang
dc.contributor.authorArias, Cesar A
dc.date.accessioned2020-05-13T20:07:57Z
dc.date.available2020-05-13T20:07:57Z
dc.date.issued2012
dc.description.abstractenglishBackground The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes involved in cell envelope homeostasis and phospholipid metabolism. Here we characterized changes in CM phospholipid profiles associated with development of DAP resistance in clinical enterococcal strains. Methodology Using two clinical strain-pairs of DAP-susceptible and DAP-resistant E. faecalis (S613 vs. R712) and E. faecium (S447 vs. R446) recovered before and after DAP therapy, we compared four distinct CM profiles: phospholipid content, fatty acid composition, membrane fluidity and capacity to be permeabilized and/or depolarized by DAP. Additionally, we characterized the cell envelope of the E. faecium strain-pair by transmission electron microscopy and determined the relative cell surface charge of both strain-pairs. Principal Findings Both E. faecalis and E. faecium mainly contained four major CM PLs: phosphatidylglycerol (PG), cardiolipin, lysyl-phosphatidylglycerol (L-PG) and glycerolphospho-diglycodiacylglycerol (GP-DGDAG). In addition, E. faecalis CMs (but not E. faecium) also contained: i) phosphatidic acid; and ii) two other unknown species of amino-containing PLs. Development of DAP resistance in both enterococcal species was associated with a significant decrease in CM fluidity and PG content, with a concomitant increase in GP-DGDAG. The strain-pairs did not differ in their outer CM translocation (flipping) of amino-containing PLs. Fatty acid content did not change in the E. faecalis strain-pair, whereas a significant decrease in unsaturated fatty acids was observed in the DAP-resistant E. faecium isolate R446 (vs S447). Resistance to DAP in E. faecium was associated with distinct structural alterations of the cell envelope and cell wall thickening, as well as a decreased ability of DAP to depolarize and permeabilize the CM. Conclusion Distinct alterations in PL content and fatty acid composition are associated with development of enterococcal DAP resistance.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0043958
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/20.500.12495/2709
dc.language.isoeng
dc.publisherPublic Library of Sciencespa
dc.publisher.journalPlos onespa
dc.relation.ispartofseriesPlos one, 1932-6203. Vol, 7. Nro, 8, 2012spa
dc.relation.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043958
dc.rights.creativecommons2012
dc.rights.localAcceso cerradospa
dc.subject.decsLipopéptidosspa
dc.subject.decsEnterococcus faecalisspa
dc.subject.decsFarmacorresistencia microbianaspa
dc.titleDaptomycin resistance in enterococci Is associated with distinct alterations of cell membrane phospholipid contentspa
dc.typearticlespa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localartículospa

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