The phosphate regulon and bacterial virulence: a regulatory network connecting phosphate homeostasis and pathogenesis

• Published in: FEMS microbiology reviews Vol. 32; no. 3; pp. 461 - 473
• Main Authors: Lamarche, Martin G., Wanner, Barry L., Crépin, Sébastien, Harel, Josée
• Format: Journal Article
• Language: English
• Published: Oxford, UK Federation of European Microbiological Societies 01.05.2008; Blackwell Publishing Ltd; Blackwell
• Subjects: ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Bacteria - genetics; Bacteria - metabolism; Bacteria - pathogenicity; Bacterial Physiological Phenomena; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; bacterial virulence; Bacteriology; Biofilms - growth & development; Biological and medical sciences; cross‐regulation; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; Homeostasis; Microbiology; Miscellaneous; Pho regulon; Phosphates - metabolism; Pst system; Regulon; stochastic activation; stress responses; Virulence; Pho regulon; bacterial virulence; stochastic activation; Pst system; cross-regulation; stress responses; Phosphorylation; Enzyme; Pathogenesis; Transferases; Virulence; Review; Gene expression; Nutrient starvation; Protein; Stress; Regulation(control); Histidine; Gene; Kinase; Aminoacid; Bacteria; Environment
• ISSN: 0168-6445; 1574-6976; 1574-6976
• DOI: 10.1111/j.1574-6976.2008.00101.x

Abstract Bacterial pathogens regulate virulence factor gene expression coordinately in response to environmental stimuli, including nutrient starvation. The phosphate (Pho) regulon plays a key role in phosphate homeostasis. It is controlled by the PhoR/PhoB two-component regulatory system. PhoR is an integral membrane signaling histidine kinase that, through an interaction with the ABC-type phosphate-specific transport (Pst) system and a protein called PhoU, somehow senses environmental inorganic phosphate (Pi) levels. Under conditions of Pi limitation (or in the absence of a Pst component or PhoU), PhoR activates its partner response regulator PhoB by phosphorylation, which, in turn, up- or down-regulates target genes. Single-cell profiling of PhoB activation has shown recently that Pho regulon gene expression exhibits a stochastic, ‘all-or-none,’ behavior. Recent studies have also shown that the Pho regulon plays a role in the virulence of several bacteria. Here, we present a comprehensive overview of the role of the Pho regulon in bacterial virulence. The Pho regulon is clearly not a simple regulatory circuit for controlling phosphate homeostasis; it is part of a complex network important for both bacterial virulence and stress response.