Dataset Information

PhoB regulates both environmental and virulence gene expression in Vibrio cholerae.

ABSTRACT: 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.

SUBMITTER: Pratt JT

PROVIDER: S-EPMC2981138 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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PhoB regulates both environmental and virulence gene expression in Vibrio cholerae.

Pratt Jason T JT Ismail Ayman M AM Camilli Andrew A

Molecular microbiology 20100816 6

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 ind ...[more]

PMID: 20659293

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Project description:A fundamental, but unanswered question in host-pathogen interactions is the timing, localization and population distribution of virulence gene expression during infection. Here, microarray and in situ single cell expression methods were used to study Vibrio cholerae growth and virulence gene expression during infection of the rabbit ligated ileal loop model of cholera. Genes encoding the toxin-coregulated pilus (TCP) and cholera toxin (CT) were powerfully expressed early in the infectious process in bacteria adjacent to epithelial surfaces. Increased growth was found to co-localize with virulence gene expression. Significant heterogeneity in the expression of tcpA, the repeating subunit of TCP, was observed late in the infectious process. The expression of tcpA, studied in single cells in a homogeneous medium, demonstrated unimodal induction of tcpA after addition of bicarbonate, a chemical inducer of virulence gene expression. Striking bifurcation of the population occurred during entry into stationary phase: one subpopulation continued to express tcpA, whereas the expression declined in the other subpopulation. ctxA, encoding the A subunit of CT, and toxT, encoding the proximal master regulator of virulence gene expression also exhibited the bifurcation phenotype. The bifurcation phenotype was found to be reversible, epigenetic and to persist after removal of bicarbonate, features consistent with bistable switches. The bistable switch requires the positive-feedback circuit controlling ToxT expression and formation of the CRP-cAMP complex during entry into stationary phase. Key features of this bistable switch also were demonstrated in vivo, where striking heterogeneity in tcpA expression was observed in luminal fluid in later stages of the infection. When this fluid was diluted into artificial seawater, bacterial aggregates continued to express tcpA for prolonged periods of time. The bistable control of virulence gene expression points to a mechanism that could generate a subpopulation of V. cholerae that continues to produce TCP and CT in the rice water stools of cholera patients.

Dataset Information

PhoB regulates both environmental and virulence gene expression in Vibrio cholerae.

Publications

PhoB regulates both environmental and virulence gene expression in Vibrio cholerae.

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