B-180. PhoB Negatively Regulates Virulence Gene Expression in Vibrio cholerae

J. Pratt1, A. Camilli1,2;
1Tufts Univ. Sch. of Med., Boston, MA, 2Howard Hughes Med. Inst., Boston, MA.

Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, is naturally found in temperate waters around the world. Aquatic environments are generally limited for phosphate, suggesting that the ability to regulate phosphate transport and utilization is key for the survival of V. cholerae in its natural environment. Bacteria such as V. cholerae and Escherichia coli encode a co-regulated set of genes, known as the Pho regulon, which is induced in conditions of low phosphate concentration and code for proteins involved in transport and metabolism of phosphate-containing compounds. Expression of the Pho regulon is regulated by the PhoBR two- component system, where PhoB represents a DNA-binding response regulator. The ability of V. cholerae to survive in two very different environments, aquatic and host small intestine, requires tight regulation of genes essential for growth in each environment. A recent study shows that V. cholerae induces genes late in infection of the host small intestine that are required for growth in its natural environment, suggesting that the bacterium is preparing for the next stage of its life cycle. Some of the genes induced late in infection are members of the Pho regulon. We have shown that not only is PhoB required for survival in pond water, but that it also negatively regulates virulence gene expression and is required for colonization of the infant mouse small intestine. Thus, the PhoBR two-component system represents a necessary function for the bacterium in both environments.