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PNAS 99 (5): 3129-3134

Copyright © 2002 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / MICROBIOLOGY

Quorum-sensing regulators control virulence gene expression in Vibrio cholerae

Jun Zhu*, Melissa B. Miller{dagger}, Russell E. Vance*, Michelle Dziejman*, Bonnie L. Bassler{dagger}, and John J. Mekalanos*,{ddagger}

*Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; and {dagger}Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014

Contributed by John J. Mekalanos

Accepted for publication December 21, 2001.

Abstract: The production of virulence factors including cholera toxin and the toxin-coregulated pilus in the human pathogen Vibrio cholerae is strongly influenced by environmental conditions. The well-characterized ToxR signal transduction cascade is responsible for sensing and integrating the environmental information and controlling the virulence regulon. We show here that, in addition to the known components of the ToxR signaling circuit, quorum-sensing regulators are involved in regulation of V. cholerae virulence. We focused on the regulators LuxO and HapR because homologues of these two proteins control quorum sensing in the closely related luminous marine bacterium Vibrio harveyi. Using an infant mouse model, we found that a luxO mutant is severely defective in colonization of the small intestine. Gene arrays were used to profile transcription in the V. cholerae wild type and the luxO mutant. These studies revealed that the ToxR regulon is repressed in the luxO mutant, and that this effect is mediated by another negative regulator, HapR. We show that LuxO represses hapR expression early in log-phase growth, and constitutive expression of hapR blocks ToxR-regulon expression. Additionally, LuxO and HapR regulate a variety of other cellular processes including motility, protease production, and biofilm formation. Together these data suggest a role for quorum sensing in modulating expression of blocks of virulence genes in a reciprocal fashion in vivo.


{ddagger} To whom reprint requests should be addressed. E-mail: john_mekalanos{at}hms.harvard.edu.

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N-Acyl-L-Homoserine Lactone Quorum Sensing Controls Butanediol Fermentation in Serratia plymuthica RVH1 and Serratia marcescens MG1.
R. Van Houdt, P. Moons, M. Hueso Buj, and C. W. Michiels (2006)
J. Bacteriol. 188, 4570-4572
   Abstract »    Full Text »    PDF »
A Vibrio cholerae protease needed for killing of Caenorhabditis elegans has a role in protection from natural predator grazing.
K. Vaitkevicius, B. Lindmark, G. Ou, T. Song, C. Toma, M. Iwanaga, J. Zhu, A. Andersson, M.-L. Hammarstrom, S. Tuck, et al. (2006)
PNAS 103, 9280-9285
   Abstract »    Full Text »    PDF »
Bundle-Forming Pili and EspA Are Involved in Biofilm Formation by Enteropathogenic Escherichia coli.
C. G. Moreira, K. Palmer, M. Whiteley, M. P. Sircili, L. R. Trabulsi, A. F. P. Castro, and V. Sperandio (2006)
J. Bacteriol. 188, 3952-3961
   Abstract »    Full Text »    PDF »
Contribution of Hemagglutinin/Protease and Motility to the Pathogenesis of El Tor Biotype Cholera.
A. J. Silva, G. J. Leitch, A. Camilli, and J. A. Benitez (2006)
Infect. Immun. 74, 2072-2079
   Abstract »    Full Text »    PDF »
The Transcriptional Regulator VqmA Increases Expression of the Quorum-Sensing Activator HapR in Vibrio cholerae.
Z. Liu, A. Hsiao, A. Joelsson, and J. Zhu (2006)
J. Bacteriol. 188, 2446-2453
   Abstract »    Full Text »    PDF »
Three New Regulators of Swarming in Vibrio parahaemolyticus.
S. Jaques and L. L. McCarter (2006)
J. Bacteriol. 188, 2625-2635
   Abstract »    Full Text »    PDF »
Increased Chatter: Cyclic Dipeptides as Molecules of Chemical Communication in Vibrio spp..
K. E. Klose (2006)
J. Bacteriol. 188, 2025-2026
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Cyclo(Phe-Pro) Modulates the Expression of ompU in Vibrio spp..
D.-K. Park, K.-E. Lee, C.-H. Baek, I. H. Kim, J.-H. Kwon, W. K. Lee, K.-H. Lee, B.-S. Kim, S.-H. Choi, and K.-S. Kim (2006)
J. Bacteriol. 188, 2214-2221
   Abstract »    Full Text »    PDF »

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