The Vibrio cholerae var regulon encodes a metallo-beta-lactamase and an antibiotic efflux pump, which are regulated by VarR, a LysRtype transcription factor

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dc.citation.issue9
dc.citation.volume12
dc.contributor.authorLin, Hong-Ting Victor
dc.contributor.authorMassam-Wu, Teresa
dc.contributor.authorLin, Chen-Ping
dc.contributor.authorWang, Yen-Jen Anna
dc.contributor.authorShen, Yu-Chi
dc.contributor.authorLu, Wen-Jung
dc.contributor.authorHsu, Pang-Hung
dc.contributor.authorChen, Yu-Hou
dc.contributor.authorBorges-Walmsley, Maria Ines [UNIFESP]
dc.contributor.authorWalmsley, Adrian Robert [UNIFESP]
dc.coverageSan Francisco
dc.date.accessioned2020-08-04T13:40:12Z
dc.date.available2020-08-04T13:40:12Z
dc.date.issued2017
dc.description.abstractThe genome sequence of V. cholerae O1 Biovar Eltor strain N16961 has revealed a putative antibiotic resistance (var) regulon that is predicted to encode a transcriptional activator (VarR), which is divergently transcribed relative to the putative resistance genes for both a metallo-beta-lactamase (VarG) and an antibiotic efflux-pump (VarABCDEF). We sought to test whether these genes could confer antibiotic resistance and are organised as a regulon under the control of VarR. VarG was overexpressed and purified and shown to have beta-lactamase activity against penicillins, cephalosporins and carbapenems, having the highest activity against meropenem. The expression of VarABCDEF in the Escherichia coli (Delta acrAB) strain KAM3 conferred resistance to a range of drugs, but most significant resistance was to the macrolide spiramycin. A gel-shift analysis was used to determine if VarR bound to the promoter regions of the resistance genes. Consistent with the regulation of these resistance genes, VarR binds to three distinct intergenic regions, varRG, varGA and varBC located upstream and adjacent to varG, varA and varC, respectively. VarR can act as a repressor at the varRG promoter region whilst this repression was relieved upon addition of beta-lactams, these did not dissociate the VarR/varRG-DNA complex, indicating that the derepression of varR by beta-lactams is indirect. Considering that the genomic arrangement of VarR-VarG is strikingly similar to that of AmpR-AmpC system, it is possible that V. cholerae has evolved a system for resistance to the newer beta-lactams that would prove more beneficial to the bacterium in light of current selective pressures.en
dc.description.affiliationNatl Taiwan Ocean Univ, Dept Food Sci, Keelung, Taiwan
dc.description.affiliationNatl Taiwan Ocean Univ, Ctr Excellence Oceans, Keelung, Taiwan
dc.description.affiliationUniv Durham, Dept Biosci, Durham, England
dc.description.affiliationNatl Taiwan Ocean Univ, Dept Biosci & Biotechnol, Keelung, Taiwan
dc.description.affiliationAcad Sinica, Inst Biol Chem, Taipei, Taiwan
dc.description.affiliationUniv Fed Sao Paulo, UNIFESP, Dept Bioquim, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, UNIFESP, Dept Bioquim, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipMinistry of Science and Technology (Taiwan)
dc.description.sponsorshipWellcome Trust (UK)
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0184255
dc.identifier.citationPlos One. San Francisco, v. 12, n. 9, 2017.
dc.identifier.doi10.1371/journal.pone.0184255
dc.identifier.fileWOS000410449500019.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57362
dc.identifier.wosWOS:000410449500019
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleThe Vibrio cholerae var regulon encodes a metallo-beta-lactamase and an antibiotic efflux pump, which are regulated by VarR, a LysRtype transcription factoren
dc.typeinfo:eu-repo/semantics/article
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