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Substrate-dependent activation of the Vibrio cholerae vexAB RND efflux system requires vexR

Taylor, DL and Ante, VM and Bina, XR and Howard, MF and Bina, JE (2015) Substrate-dependent activation of the Vibrio cholerae vexAB RND efflux system requires vexR. PLoS ONE, 10 (2).

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Abstract

© 2015 Taylor et al. Vibrio cholerae encodes six resistance-nodulation-division (RND) efflux systems which function in antimicrobial resistance, virulence factor production, and intestinal colonization. Among the six RND efflux systems, VexAB exhibited broad substrate specificity and played a predominant role in intrinsic antimicrobial resistance. The VexAB system was encoded in an apparent three gene operon that included vexR; which encodes an uncharacterized TetR family regulator. In this work we examined the role of vexR in vexRAB expression. We found that VexR bound to the vexRAB promoter and vexR deletion resulted in decreased vexRAB expression and increased susceptibility to VexAB antimicrobial substrates. Sub-strate-dependent induction of vexRAB was dependent on vexR and episomal vexR expression provided a growth advantage in the presence of the VexAB substrate deoxycholate. The expression of vexRAB increased, in a vexR-dependent manner, in response to the loss of RND efflux activity. This suggested that VexAB may function to export intracellular metabolites. Support for this hypothesis was provided by data showing that vexRAB was upregulated in several metabolic mutants including tryptophan biosynthetic mutants that were predicted to accumulate indole. In addition, vexRAB was found to be upregulated in response to exogenous indole and to contribute to indole resistance. The collective results indicate that vexR is required for vexRAB expression in response to VexAB substrates and that the VexAB RND efflux system modulates the intracellular levels of metabolites that could otherwise accumulate to toxic levels.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Taylor, DL
Ante, VMvma4@pitt.eduVMA4
Bina, XR
Howard, MF
Bina, JEjbina@pitt.eduJBINA
Date: 19 February 2015
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0117890
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
Other ID: NLM PMC4335029
PubMed Central ID: PMC4335029
PubMed ID: 25695834
Date Deposited: 12 May 2015 18:12
Last Modified: 13 Oct 2017 22:56
URI: http://d-scholarship.pitt.edu/id/eprint/24097

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