A liar deletion restores susceptibility to daptomycin and antimicrobial peptides in multidrug-resistant enterococcus faecalis

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dc.contributor.authorReyes, Jinnethe
dc.contributor.authorPanesso, Diana
dc.contributor.authorTran, Truc T.
dc.contributor.authorMishra, Nagendra N.
dc.contributor.authorCruz, Melissa R.
dc.contributor.authorMunita, Jose M.
dc.contributor.authorSingh, Kavindra V.
dc.contributor.authorYeaman, Michael R.
dc.contributor.authorMurray, Barbara E.
dc.contributor.authorShamoo, Yousif
dc.contributor.authorGarsin, Danielle
dc.contributor.authorBayer, Arnold S.
dc.contributor.authorArias, Cesar A.
dc.contributor.orcidPanesso, Diana [0000-0002-4049-9702]
dc.date.accessioned2020-08-04T21:29:00Z
dc.date.available2020-08-04T21:29:00Z
dc.date.issued2015
dc.description.abstractenglishDaptomycin is a lipopeptide antibiotic that is used clinically against many gram-positive bacterial pathogens and is considered a key frontline bactericidal antibiotic to treat multidrug-resistant enterococci. Emergence of daptomycin resistance during therapy of serious enterococcal infections is a major clinical issue. In this work, we show that deletion of the gene encoding the response regulator, LiaR (a member of the LiaFSR system that controls cell envelope homeostasis), from daptomycin-resistant Enterococcus faecalis not only reversed resistance to 2 clinically available cell membrane–targeting antimicrobials (daptomycin and telavancin), but also resulted in hypersusceptibility to these antibiotics and to a variety of antimicrobial peptides of diverse origin and with different mechanisms of action. The changes in susceptibility to these antibiotics and antimicrobial peptides correlated with in vivo attenuation in a Caenorhabditis elegans model. Mechanistically, deletion of liaR altered the localization of cardiolipin microdomains in the cell membrane. Our findings suggest that LiaR is a master regulator of the enterococcal cell membrane response to diverse antimicrobial agents and peptides; as such, LiaR represents a novel target to restore the activity of clinically useful antimicrobials against these organisms and, potentially, increase susceptibility to endogenous antimicrobial peptides.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/infdis/jiu602
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn0022-1899
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlhttps://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/3673
dc.language.isoeng
dc.publisherOxford University Pressspa
dc.publisher.journalJournal of Infectious Diseasesspa
dc.relation.ispartofseriesJournal of Infectious Diseases, 0022-1899, Vol. 211, Nro. 8, 2015, p.1317-1325spa
dc.relation.urihttps://academic.oup.com/jid/article/211/8/1317/916198
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2015-04-15
dc.rights.localAcceso abiertospa
dc.subject.keywordsLiaFSRspa
dc.subject.keywordsDaptomycinspa
dc.subject.keywordsE. faecalisspa
dc.subject.keywordsAntimicrobial peptidesspa
dc.titleA liar deletion restores susceptibility to daptomycin and antimicrobial peptides in multidrug-resistant enterococcus faecalisspa
dc.title.translatedA liar deletion restores susceptibility to daptomycin and antimicrobial peptides in multidrug-resistant enterococcus faecalisspa
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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