Journal
FEMS MICROBIOLOGY REVIEWS
Volume 32, Issue 3, Pages 461-473Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1574-6976.2008.00101.x
Keywords
Pho regulon; Pst system; bacterial virulence; cross-regulation; stress responses; stochastic activation
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Funding
- NIGMS NIH HHS [GM 62662] Funding Source: Medline
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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 (P-i) levels. Under conditions of P-i 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.
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