Quorum-sensing regulators control virulence gene expression in Vibrio cholerae

By Jun Zhu, Melissa B. Miller, R. Vance, M. Dziejman, B. Bassler, J. Mekalanos. Proceedings of the National Academy of Sciences of the United States of America, 2002

889 citations recorded by the source corpus.

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.

Subfields: Endocrinology, Health, Toxicology and Mutagenesis, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3358d3b175d4430027b2b7a35b20c1559f25a1cf

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Citations in the corpus

Bacterial quorum sensing: its role in virulence and possibilities for its control. (2012, background): “One interpretation of this finding is that establishing a biofilm community at LCD allows S. aureus time to grow to HCD and, at that point, it is optimally poised to secrete virulence factors (Yarwood et al. 2004; Boles and Horswill 2008).”
Bacterial Quorum-Sensing Network Architectures (2009, neutral): “cholerae do possess sets of quorumsensing components that are highly similar to one another (37, 57, 75, 124, 147).”
Multi-species biofilms: living with friendly neighbors. (2012, background): “Quorum sensing has been shown to play an important role in the development of biofilms (Davies et al., 1998; Singh et al., 2000; Zhu et al., 2002; Riedel et al., 2009; Bjarnsholt et al., 2010), although its impact, namely induction vs.”
Biofilms: the matrix revisited. (2005, background): “Importantly, expression of hapR itself is indirectly repressed by LuxO, a two-component response regulator that is most active under conditions of low cell density [ 39 ].”
Quorum sensing controls biofilm formation in Vibrio cholerae (2003, methodology): “1 and Miller et al., 2002; Zhu et al., 2002).”
Quorum sensing: cell-to-cell communication in bacteria. (2005, background): “F or p er so na l u se o nl y. ANRV255-CB21-14 ARI 1 September 2005 13:7 SAH: S-adenosylhomocysteine DPD: 4,5-dihydroxy-2,3pentonedione, a molecule generated by LuxS the entire virulence regulon (>70 genes) is repressed by quorum sensing (Zhu et al. 2002).”
The myriad roles of cyclic AMP in microbial pathogens, from signal to sword (2011, background): “cholerae El Tor strains, which lack a functional HapR owing to the presence of a frameshift mutatio”