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dc.contributor.authorRincon Núñez, Sandra
dc.contributor.authorPanesso, Diana
dc.contributor.authorMiller, William R
dc.contributor.authorSingh, Kavindra V
dc.contributor.authorCruz, Melissa R
dc.contributor.authorKhan, Ayesha
dc.contributor.authorDinh, An Q
dc.contributor.authorDiaz, Lorena
dc.contributor.authorRios, Rafael
dc.contributor.authorShamoo, Yousif
dc.contributor.authorReyes, Jinnethe
dc.contributor.authorTran, Truc T
dc.contributor.authorGarsin, Danielle A
dc.contributor.authorArias, Cesar A
dc.date.accessioned2020-05-12T21:30:35Z
dc.date.available2020-05-12T21:30:35Z
dc.identifier.issn0022-1899spa
dc.identifier.urihttp://hdl.handle.net/20.500.12495/2650
dc.format.mimetypeapplication/pdfspa
dc.language.isoengspa
dc.publisherOxford University Pressspa
dc.relation.ispartofseriesJournal of Infectious Diseases, 0022-1899, Vol 220, Num 3, 2019, Pag 494–504spa
dc.relation.urihttps://academic.oup.com/jid/article-abstract/220/3/494/5425477?redirectedFrom=fulltextspa
dc.titleDisrupting membrane adaptation restores in vivo efficacy of antibiotics against multidrug-resistant enterococci and potentiates killing by human neutrophilsspa
dc.typearticlespa
dc.type.localartículospa
dc.subject.decsDaptomicinaspa
dc.subject.decsFarmacorresistencia microbianaspa
dc.subject.keywordsLiaRspa
dc.subject.keywordsDaptomycinspa
dc.subject.keywordsCaenorhabditis elegansspa
dc.subject.keywordsPMNsspa
dc.subject.keywordsPhagocytosisspa
dc.identifier.doihttps://doi.org/10.1093/infdis/jiz131spa
dc.subject.armarcEstrésspa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.publisher.journalJournal of Infectious Diseasesspa
dc.contributor.orcidPanesso, Diana [0000-0002-4049-9702]
dc.contributor.orcidRincon Núñez, Sandra [0000-0002-8482-4554]
dc.title.translatedDisrupting membrane adaptation restores in vivo efficacy of antibiotics against multidrug-resistant enterococci and potentiates killing by human neutrophilsspa
dc.description.abstractenglishDaptomycin resistance in enterococci is often mediated by the LiaFSR system, which orchestrates the cell membrane stress response. Activation of LiaFSR through the response regulator LiaR generates major changes in cell membrane function and architecture (membrane adaptive response), permitting the organism to survive the antibiotic attack. Here, using a laboratory strain of Enterococcus faecalis, we developed a novel Caenorhabditis elegans model of daptomycin therapy and showed that disrupting LiaR-mediated cell membrane adaptation restores the in vivo activity of daptomycin. The LiaR effect was also seen in a clinical strain of daptomycin-resistant Enterococcus faecium, using a murine model of peritonitis. Furthermore, alteration of the cell membrane response increased the ability of human polymorphonuclear neutrophils to readily clear both E. faecalis and multidrug-resistant E. faecium. Our results provide proof of concept that targeting the cell membrane adaptive response restores the in vivo activity of antibiotics, prevents resistance, and enhances the ability of the innate immune system to kill infecting bacteria.spa
dc.rights.localAcceso cerradospa
dc.rights.creativecommons2019


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