Quorum-sensing regulators control virulence gene expression in Vibrio cholerae.

TitleQuorum-sensing regulators control virulence gene expression in Vibrio cholerae.
Publication TypeJournal Article
Year of Publication2002
AuthorsZhu, J, Miller, MB, Vance, RE, Dziejman, M, Bassler, BL, Mekalanos, JJ
JournalProc Natl Acad Sci U S A
Volume99
Issue5
Pagination3129-34
Date Published2002 Mar 05
ISSN0027-8424
KeywordsAnimals, Bacterial Proteins, Cholera, Disease Models, Animal, DNA-Binding Proteins, Gene Expression Regulation, Bacterial, Genes, Bacterial, Humans, Mice, Mice, Inbred C57BL, Repressor Proteins, Trans-Activators, Transcription Factors, Vibrio cholerae, Virulence
Abstract

<p>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.</p>

DOI10.1073/pnas.052694299
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID11854465
PubMed Central IDPMC122484
Grant ListR01 AI018045 / AI / NIAID NIH HHS / United States
R37 AI018045 / AI / NIAID NIH HHS / United States
AI18045 / AI / NIAID NIH HHS / United States