Vibrio cholerae vexH encodes a multiple drug efflux pump that contributes to the production of cholera toxin and the toxin co-regulated pilus

Taylor, DL and Bina, XR and Bina, JE (2012) Vibrio cholerae vexH encodes a multiple drug efflux pump that contributes to the production of cholera toxin and the toxin co-regulated pilus. PLoS ONE, 7 (5).

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Abstract

The resistance-nodulation-division (RND) efflux systems are ubiquitous transporters that function in antimicrobial resistance. Recent studies showed that RND systems were required for virulence factor production in Vibrio cholerae. The V. cholerae genome encodes six RND efflux systems. Three of the RND systems (VexB, VexD, and VexK) were previously shown to be redundant for in vitro resistance to bile acids and detergents. A mutant lacking the VexB, VexD, and VexK RND pumps produced wild-type levels of cholera toxin (CT) and the toxin co-regulated pilus (TCP) and was moderately attenuated for intestinal colonization. In contrast, a RND negative mutant produced significantly reduced amounts of CT and TCP and displayed a severe colonization defect. This suggested that one or more of the three uncharacterized RND efflux systems (i.e. VexF, VexH, and VexM) were required for pathogenesis. In this study, a genetic approach was used to generate a panel of V. cholerae RND efflux pump mutants in order to determine the function of VexH in antimicrobial resistance, virulence factor production, and intestinal colonization. VexH contributed to in vitro antimicrobial resistance and exhibited a broad substrate specificity that was redundant with the VexB, VexD, and VexK RND efflux pumps. These four efflux pumps were responsible for in vitro antimicrobial resistance and were required for virulence factor production and intestinal colonization. Mutation of the VexF and/or VexM efflux pumps did not affect in vitro antimicrobial resistance, but did negatively affect CT and TCP production. Collectively, our results demonstrate that the V. cholerae RND efflux pumps have redundant functions in antimicrobial resistance and virulence factor production. This suggests that the RND efflux systems contribute to V. cholerae pathogenesis by providing the bacterium with protection against antimicrobial compounds that are present in the host and by contributing to the regulated expression of virulence factors. © 2012 Taylor et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Taylor, DL Bina, XR xrb1@pitt.edu XRB1 Bina, JE jbina@pitt.edu JBINA
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Vadivelu, Jamunarani UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	30 May 2012
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	7
Number:	5
DOI or Unique Handle:	10.1371/journal.pone.0038208
Refereed:	Yes
PubMed Central ID:	PMC3364225
PubMed ID:	22666485
Date Deposited:	11 Jul 2012 18:09
Last Modified:	26 Jan 2019 18:55
URI:	http://d-scholarship.pitt.edu/id/eprint/12712

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