This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bina, X. R.
Right arrow Articles by Bina, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bina, X. R.
Right arrow Articles by Bina, J. E.
Right arrowPubmed/NCBI databases
*Substance via MeSH

 Previous Article  |  Next Article 

Infection and Immunity, August 2008, p. 3595-3605, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.01620-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Vibrio cholerae RND Family Efflux Systems Are Required for Antimicrobial Resistance, Optimal Virulence Factor Production, and Colonization of the Infant Mouse Small Intestine{triangledown}

Xiaowen R. Bina,1,{dagger} Daniele Provenzano,2,{dagger} Nathalie Nguyen,1 and James E. Bina1*

Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, Tennessee 38163,1 Center for Biomedical Studies and Department of Biological Sciences, University of Texas—Brownsville, 80 Fort Brown, Brownsville, Texas 785202

Received 6 December 2007/ Returned for modification 27 January 2008/ Accepted 13 May 2008

Vibrio cholerae is a gram-negative human intestinal pathogen that causes the diarrheal disease cholera. Humans acquire cholera by ingesting V. cholerae-contaminated food or water. Upon ingestion, V. cholerae encounters several barriers to colonization, including bile acid toxicity and antimicrobial products of the innate immune system. In many gram-negative bacteria, resistance to the antimicrobial effects of these products is mediated by RND (resistance-nodulation-division) family efflux systems. In this study we tested the hypothesis that the V. cholerae RND efflux systems are required for antimicrobial resistance and virulence. The six V. cholerae genes encoding RND efflux pumps were deleted from the genome of the O1 El Tor strain N16961, resulting in the generation of 14 independent RND deletion mutants, including one RND-null strain. Determination of the antimicrobial susceptibilities of the mutants revealed that the RND efflux systems were responsible for resistance to multiple antimicrobial compounds, including bile acids, antimicrobial peptides, and antibiotics. VexB (VC0164) was found to be the RND efflux pump primarily responsible for the resistance of V. cholerae to multiple antimicrobial compounds in vitro. In contrast, VexD (VC1757) and VexK (VC1673) encoded efflux pumps with detergent-specific substrate specificities that were redundant with VexB. A strain lacking VexB, VexD, and VexK was attenuated in the infant mouse model, and its virulence factor production was unaffected. In contrast, a V. cholerae RND-null strain produced significantly less cholera toxin and fewer toxin-coregulated pili than the wild type and was unable to colonize the infant mouse. The decreased virulence factor production in the RND-null strain was linked to reduced transcription of tcpP and toxT. Our findings show that the V. cholerae RND efflux systems are required for antimicrobial resistance, optimal virulence factor production, and colonization of the infant mouse.

* Corresponding author. Mailing address: Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163. Phone: (901) 448-1786. Fax: (901) 448-7360. E-mail: JBina{at}utmem.edu

{triangledown} Published ahead of print on 19 May 2008.

Editor: A. Camilli

{dagger} X.R.B. and D.P. contributed equally to this study.

Infection and Immunity, August 2008, p. 3595-3605, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.01620-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bina, X. R., Philippart, J. A., Bina, J. E. (2009). Effect of the efflux inhibitors 1-(1-naphthylmethyl)-piperazine and phenyl-arginine-{beta}-naphthylamide on antimicrobial susceptibility and virulence factor production in Vibrio cholerae. J Antimicrob Chemother 63: 103-108 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»