CpxR activates MexAB-OprM efflux pump expression and enhances antibiotic resistance in both laboratory and clinical nalB-type isolates of Pseudomonas aeruginosa

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dc.contributor.authorTian, Zhe-Xian
dc.contributor.authorYi, Xue-Xian
dc.contributor.authorCho, Anna
dc.contributor.authorO'Gara, Fergal
dc.contributor.authorWang, Yi-Ping
dc.contributor.funderNational Natural Science Foundation of Chinaen
dc.contributor.funderState Key Laboratory of Protein and Plant Gene Research, China
dc.contributor.funderNational Science Fund for Distinguished Young Scholars, China
dc.date.accessioned2016-10-26T09:01:12Z
dc.date.available2016-10-26T09:01:12Z
dc.date.issued2016-10-13
dc.description.abstractResistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. In this study, we demonstrate that CpxR, previously identified as a regulator of the cell envelope stress response in Escherichia coli, is directly involved in activation of expression of RND efflux pump MexAB-OprM in P. aeruginosa. A conserved CpxR binding site was identified upstream of the mexA promoter in all genome-sequenced P. aeruginosa strains. CpxR is required to enhance mexAB-oprM expression and drug resistance, in the absence of repressor MexR, in P. aeruginosa strains PA14. As defective mexR is a genetic trait associated with the clinical emergence of nalB-type multidrug resistance in P. aeruginosa during antibiotic treatment, we investigated the involvement of CpxR in regulating multidrug resistance among resistant isolates generated in the laboratory via antibiotic treatment and collected in clinical settings. CpxR is required to activate expression of mexAB-oprM and enhances drug resistance, in the absence or presence of MexR, in ofloxacin-cefsulodin-resistant isolates generated in the laboratory. Furthermore, CpxR was also important in the mexR-defective clinical isolates. The newly identified regulatory linkage between CpxR and the MexAB-OprM efflux pump highlights the presence of a complex regulatory network modulating multidrug resistance in P. aeruginosa.en
dc.description.sponsorshipNational Science Foundation of China (Grant Nos. 31270127 and 81071398); State Key Laboratory of Protein and Plant Gene Research, China (Grant B02); National Science Fund for Distinguished Young Scholars, China (Grant No. 39925017)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide1005932
dc.identifier.citationTian, Z.-X., Yi, X.-X., Cho, A., O’Gara, F. and Wang, Y.-P. (2016) 'CpxR activates MexAB-OprM efflux pump expression and enhances antibiotic resistance in both laboratory and clinical nalB-type isolates of Pseudomonas aeruginosa', PLoS Pathogens, 12(10), e1005932 (22pp). doi:10.1371/journal.ppat.1005932en
dc.identifier.doi10.1371/journal.ppat.1005932
dc.identifier.endpage22en
dc.identifier.issn1553-7366
dc.identifier.issued10en
dc.identifier.journaltitlePLoS Pathogensen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/3214
dc.identifier.volume12en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights© 2016, Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectMultidrug resistanceen
dc.subjectAntibioticen
dc.subjectRegulatoryen
dc.titleCpxR activates MexAB-OprM efflux pump expression and enhances antibiotic resistance in both laboratory and clinical nalB-type isolates of Pseudomonas aeruginosaen
dc.typeArticle (peer-reviewed)en
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