Daptomycin resistance in enterococcus faecium can be delayed by disruption of the LiaFSR stress response pathway

Vista sencilla de Ć­tem
dc.contributor.authorPrater, Amy G.
dc.contributor.authorMehta, Heer H.
dc.contributor.authorBeabout, Kathryn
dc.contributor.authorSupandy, Adeline
dc.contributor.authorMiller, William R.
dc.contributor.authorTran, Truc T.
dc.contributor.authorArias, Cesar A.
dc.contributor.authorShamoo, Yousif
dc.contributor.orcidPrater, Amy G. [0000-0001-6618-5130]
dc.contributor.orcidMiller, William R. [0000-0002-1518-2973]
dc.date.accessioned2022-02-02T20:36:11Z
dc.date.available2022-02-02T20:36:11Z
dc.date.issued2021
dc.description.abstractenglishThe LiaFSR signaling pathway plays a major role in mediating daptomycin (DAP) resistance for both Enterococcus faecalis and Enterococcus faecium. LiaFSR inhibition induces DAP hypersusceptibility but could also potentially delay the acquisition of DAP resistance in a combinatorial therapy of DAP with a LiaFSR inhibitor. To evaluate the potential efficacy of this approach, the adaptation to DAP by both E. faecalis and E. faecium lacking a functional LiaFSR were examined. Here, clinical isolates of E. faecium with liaR deletions were evolved to DAP resistance using in vitro experimental evolution. Genomic analysis of resistant populations was used to identify both the alleles and their relative frequencies in driving DAP resistance. Microscopic and biochemical analyses were then employed to investigate how those adaptive alleles contributed to DAP resistance. We found that deletion of liaR from the E. faecium genome significantly delayed the onset of DAP resistance. Unsurprisingly, resistance strategies emerged eventually. These alternative strategies were influenced by both environment and ancestral genome. The delay in the acquisition of DAP resistance when liaR was deleted supports the concept of developing a LiaFSR pathway inhibitor to prolong DAP efficacy against enterococci. The loss of a functional LiaFSR pathway reset the adaptive landscape and forced adaptation to progress in new ways that were slower in providing DAP tolerance. The observed adaptive trajectories were strongly influenced by both the environment and ancestral genome.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1128/AAC.01317-20
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1098-6596
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/6719
dc.language.isoeng
dc.publisherAmerican Society for Microbiologyspa
dc.publisher.journalAntimicrobial Agents and Chemotherapyspa
dc.relation.ispartofseriesAntimicrobial Agents and Chemotherapy; 1098-6596, Mar 18, 65(4), 2021, e01317-20spa
dc.relation.urihttps://www.biorxiv.org/content/10.1101/2020.06.23.168401v1
dc.rightsAttribution-NoDerivatives 4.0 Internacional*
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by-nd/4.0/*
dc.subjectEnterococospa
dc.subjectResistencia antibiĆ³ticaspa
dc.subjectDaptomicinaspa
dc.subjectEvoluciĆ³n de la resistencia a los medicamentosspa
dc.subject.keywordsEnterococcusspa
dc.subject.keywordsAntibiotic resistancespa
dc.subject.keywordsDaptomycinspa
dc.subject.keywordsDrug resistance evolutionspa
dc.titleDaptomycin resistance in enterococcus faecium can be delayed by disruption of the LiaFSR stress response pathwayspa
dc.title.translatedDaptomycin resistance in enterococcus faecium can be delayed by disruption of the LiaFSR stress response pathwayspa
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.localArtĆ­culo de revista

Archivos

Bloque original
Mostrando 1 - 1 de 1
Miniatura
Nombre:
Prater_Amy_G_2021.pdf
TamaƱo:
1.61 MB
Formato:
Adobe Portable Document Format
DescripciĆ³n:
Daptomycin resistance in Enterococcus faecium can be delayed by disruption of the LiaFSR stress response pathway
Descargar
Bloque de licencias
Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
license.txt
TamaƱo:
1.71 KB
Formato:
Item-specific license agreed upon to submission
DescripciĆ³n:
Descargar

Colecciones

ArtĆ­culos