A novel phosphodiesterase of the GdpP family modulates cyclic di-AMP levels in response to cell membrane stress in daptomycin-resistant enterococci

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dc.contributor.authorWang, Xu
dc.contributor.authorDavlieva, Milya
dc.contributor.authorReyes, Jinnethe
dc.contributor.authorPanesso, Diana
dc.contributor.authorArias, Cesar A.
dc.contributor.authorShamoo, Yousif
dc.contributor.orcidPanesso, Diana [0000-0002-4049-9702]
dc.date.accessioned2020-11-23T20:16:14Z
dc.date.available2020-11-23T20:16:14Z
dc.date.issued2020
dc.description.abstractenglishSubstitutions in the LiaFSR membrane stress pathway are frequently associated with the emergence of antimicrobial peptide resistance in both Enterococcus faecalis and Enterococcus faecium Cyclic di-AMP (c-di-AMP) is an important signal molecule that affects many aspects of bacterial physiology, including stress responses. We have previously identified a mutation in a gene (designated yybT) in E. faecalis that was associated with the development of daptomycin resistance, resulting in a change at position 440 (yybTI440S) in the predicted protein. Here, we show that intracellular c-di-AMP signaling is present in enterococci, and on the basis of in vitro physicochemical characterization, we show that E. faecalisyybT encodes a cyclic dinucleotide phosphodiesterase of the GdpP family that exhibits specific activity toward c-di-AMP by hydrolyzing it to 5'pApA. The E. faecalis GdpPI440S substitution reduces c-di-AMP phosphodiesterase activity more than 11-fold, leading to further increases in c-di-AMP levels. Additionally, deletions of liaR (encoding the response regulator of the LiaFSR system) that lead to daptomycin hypersusceptibility in both E. faecalis and E. faecium also resulted in increased c-di-AMP levels, suggesting that changes in the LiaFSR stress response pathway are linked to broader physiological changes. Taken together, our data show that modulation of c-di-AMP pools is strongly associated with antibiotic-induced cell membrane stress responses via changes in GdpP activity or signaling through the LiaFSR system.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1128/aac.01422-16
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/20.500.12495/5121
dc.language.isoeng
dc.publisherAmerican Society for Microbiologyspa
dc.publisher.journalAntimicrobial Agents and Chemotherapyspa
dc.relation.ispartofseriesAntimicrobial Agents and Chemotherapy, 1098-6596, Vol. 61, No. 3, 2017, p. 510-513spa
dc.relation.urihttps://aac.asm.org/content/61/3/e01422-16.long
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2017
dc.rights.localAcceso abiertospa
dc.subject.keywordsEnterococcus faecalisspa
dc.subject.keywordsEnterococcus faeciumspa
dc.subject.keywordsGdpPspa
dc.subject.keywordsLiaFSRspa
dc.subject.keywordsC-di-AMPspa
dc.subject.keywordsCyclic dinucleotidespa
dc.subject.keywordsDaptomycinspa
dc.subject.keywordsEnterococcispa
dc.subject.keywordsMembrane stressspa
dc.titleA novel phosphodiesterase of the GdpP family modulates cyclic di-AMP levels in response to cell membrane stress in daptomycin-resistant enterococcispa
dc.title.translatedA novel phosphodiesterase of the GdpP family modulates cyclic di-AMP levels in response to cell membrane stress in daptomycin-resistant 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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