PhoB regulates both environmental and virulence gene expression in Vibrio cholerae

Vibrio cholerae is a facultative pathogen that thrives in two nutritionally disparate environments, aquatic and human small intestine. Phosphate (P(i) ) is an essential nutrient that is limited in aquatic ecosystems and of unknown availability in the small intestine. Here, we show that the P(i) (Pho) regulon, which is controlled by the P(i)-specific transporter (Pst) and two-component system PhoBR, is required for V. cholerae survival in both environments, though for differing reasons. While induction of P(i) acquisition systems including Pst is critical for survival in the aquatic environment, regulation of virulence genes by PhoB and not P(i) transport per se is required for colonization of the small intestine. We show that PhoB regulates virulence genes by directly controlling expression of a key upstream transcriptional regulator, tcpPH. Thus, the Pho regulon includes virulence genes and represents a diverse gene set essential to pathogenic V. cholerae throughout its life cycle.