Genetic basis for in vivo daptomycin resistance in enterococci

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dc.contributor.authorArias, Cesar A.
dc.contributor.authorPanesso, Diana
dc.contributor.authorMcGrath, Danielle M.
dc.contributor.authorQin, Xiang
dc.contributor.authorMojica, María Fernanda
dc.contributor.authorMiller, Corwin
dc.contributor.authorDiaz, Lorena
dc.contributor.authorTran, Truc T.
dc.contributor.authorRincon Núñez, Sandra
dc.contributor.authorReyes, Jinnethe
dc.contributor.authorRoh, Jung H.
dc.contributor.authorLobos, Elizabeth
dc.contributor.authorSodergren, Erica
dc.contributor.authorPasqualini, Renata
dc.contributor.authorArap, Wadih
dc.contributor.authorQuinn, John P.
dc.contributor.authorShamoo, Yousif
dc.contributor.authorMurray, Barbara E.
dc.contributor.authorWeinstock, George M.
dc.contributor.orcidPanesso, Diana [0000-0002-4049-9702]
dc.contributor.orcidMojica, María Fernanda [0000-0002-1380-9824]
dc.contributor.orcidRincon Núñez, Sandra [0000-0002-8482-4554]
dc.date.accessioned2020-11-20T20:00:04Z
dc.date.available2020-11-20T20:00:04Z
dc.date.issued2011
dc.description.abstractenglishDaptomycin is a lipopeptide with bactericidal activity that acts on the cell membrane of enterococci and is often used off-label to treat patients infected with vancomycin-resistant enterococci. However, the emergence of resistance to daptomycin during therapy threatens its usefulness. We performed whole-genome sequencing and characterization of the cell envelope of a clinical pair of vancomycin-resistant Enterococcus faecalis isolates from the blood of a patient with fatal bacteremia; one isolate (S613) was from blood drawn before treatment and the other isolate (R712) was from blood drawn after treatment with daptomycin. The minimal inhibitory concentrations (MICs) of these two isolates were 1 and 12 μg per milliliter, respectively. Gene replacements were made to exchange the alleles found in isolate S613 with those in isolate R712. Isolate R712 had in-frame deletions in three genes. Two genes encoded putative enzymes involved in phospholipid metabolism, GdpD (which denotes glycerophosphoryl diester phosphodiesterase) and Cls (which denotes cardiolipin synthetase), and one gene encoded a putative membrane protein, LiaF (which denotes lipid II cycle-interfering antibiotics protein but whose exact function is not known). LiaF is predicted to be a member of a three-component regulatory system (LiaFSR) involved in the stress-sensing response of the cell envelope to antibiotics. Replacement of the liaF allele of isolate S613 with the liaF allele from isolate R712 quadrupled the MIC of daptomycin, whereas replacement of the gdpD allele had no effect on MIC. Replacement of both the liaF and gdpD alleles of isolate S613 with the liaF and gdpD alleles of isolate R712 raised the daptomycin MIC for isolate S613 to 12 μg per milliliter. As compared with isolate S613, isolate R712 — the daptomycin-resistant isolate — had changes in the structure of the cell envelope and alterations in membrane permeability and membrane potential. Mutations in genes encoding LiaF and a GdpD-family protein were necessary and sufficient for the development of resistance to daptomycin during the treatment of vancomycin-resistant enterococci.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1056/nejmoa1011138
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1533-4406
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlhttps://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/5104
dc.language.isoeng
dc.publisherMassachusetts Medical Societyspa
dc.publisher.journalThe New England Journal of Medicinespa
dc.relation.ispartofseriesThe New England Journal of Medicine, 1533-4406, Vol. 365, No. 10, 2011 p. 892-900spa
dc.relation.urihttps://www.nejm.org/doi/full/10.1056/nejmoa1011138#:~:text=Mutations%20in%20genes%20encoding%20LiaF,the%20National%20Institutes%20of%20Health.)
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2011
dc.rights.localAcceso abiertospa
dc.subject.keywordsAntibioticspa
dc.subject.keywordsEnterococcusspa
dc.subject.keywordsResistancespa
dc.subject.keywordsDaptomycinspa
dc.titleGenetic basis for in vivo daptomycin resistance in enterococcispa
dc.title.translatedGenetic basis for in vivo daptomycin resistance in enterococcispa
dc.type.coarhttps://purl.org/coar/resource_type/c_6501
dc.type.driverinfo:eu-repo/semantics/article
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localArtículo de revista

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