Adaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistance

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dc.contributor.authorMiller, Corwin
dc.contributor.authorKong, Jiayi
dc.contributor.authorTran, Truc T.
dc.contributor.authorArias, Cesar A.
dc.contributor.authorSaxer, Gerda
dc.contributor.authorShamoo, Yousif
dc.date.accessioned2020-07-17T18:03:00Z
dc.date.available2020-07-17T18:03:00Z
dc.date.issued2013
dc.description.abstractenglishWith increasing numbers of hospital-acquired antibiotic resistant infections each year and staggering health care costs, there is a clear need for new antimicrobial agents, as well as novel strategies to extend their clinical efficacy. While genomic studies have provided a wealth of information about the alleles associated with adaptation to antibiotics, they do not provide essential information about the relative importance of genomic changes, their order of appearance, or potential epistatic relationships between adaptive changes. Here we used quantitative experimental evolution of a single polymorphic population in continuous culture with whole-genome sequencing and allelic frequency measurements to study daptomycin (DAP) resistance in the vancomycin-resistant clinical pathogen Enterococcus faecalis S613. Importantly, we sustained both planktonic and nonplanktonic (i.e., biofilm) populations in coculture as the concentration of antibiotic was raised, facilitating the development of more ecological complexity than is typically observed in laboratory evolution. Quantitative experimental evolution revealed a clear order and hierarchy of genetic changes leading to resistance, the signaling and metabolic pathways responsible, and the relative importance of these mutations to the evolution of DAP resistance. Despite the relative simplicity of this ex vivo approach compared to the ecological complexity of the human body, we showed that experimental evolution allows for rapid identification of clinically relevant adaptive molecular pathways and new targets for drug design in pathogens.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://dx.doi.org/10.1128%2FAAC.01473-13
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1098-6596
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlhttps://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/3557
dc.language.isoeng
dc.publisherAmerican Society for Microbiologyspa
dc.publisher.journalAntimicrobial Agents and Chemotherapyspa
dc.relation.ispartofseriesAntimicrobial Agents and Chemotherapy, 1098-6596, Vol. 57, No. 11, 2013 p. 5373-5383spa
dc.relation.urihttps://aac.asm.org/content/58/1/631
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2013-11
dc.rights.localAcceso abiertospa
dc.subject.decsEnterococcus faecalisspa
dc.subject.decsDaptomicinaspa
dc.subject.decsFarmacorresistencia fúngicaspa
dc.titleAdaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistancespa
dc.title.translatedAdaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistancespa
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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