Editors' ChoicePathogenesis

Virulence Gene Expression: Fiat LuxO!

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Science's STKE  12 Mar 2002:
Vol. 2002, Issue 123, pp. tw100
DOI: 10.1126/stke.2002.123.tw100

Bacteria can monitor their population density through the perception of molecules secreted by other local bacteria. This phenomenon leads to changes in bacterial behavior and changes in gene expression, and is termed quorum sensing. Quorum sensing in Vibrio cholerae, a major pathogenic bacterium in humans, is known to exist, but the gene targets of the sensing pathway are unknown. Zhu et al. found that a two-component signal module that includes the intracellular response regulator LuxO regulates virulence genes in V. cholerae. Vibrio mutants that lacked functional LuxO produced greatly decreased amounts of virulence-associated gene products, suggesting that LuxO was important for the expression of the virulence genes. The expression of HapR, which negatively regulated the expression of virulence genes, was decreased in a LuxO-dependent manner, suggesting one mechanism by which LuxO may increase virulence gene expression indirectly.

HapR was expressed in luxO mutants, but not in wild-type bacteria, when the cells were grown at low population density, but at high density, HapR was expressed in both wild-type and in luxO bacteria in similar concentrations. Extracellular molecules that are present in high-density cultures may provide a cue that leads to decreased activity of LuxO, thus allowing the expression of HapR, and the inhibition of virulence gene expression. These results suggest a mechanism whereby V. cholerae can establish a "foothold" infection, and that once a threshold population density is reached, the expression of virulence genes is turned off.

J. Zhu, M. B. Miller, R. E. Vance, M. Dziejman, B. L. Bassler, J. J. Mekalanos, Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc. Natl. Acad. Sci. U. S. A. 99, 3129-3134 (2002). [Abstract] [Full Text]

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