Pho regulon

The Pho regulon is controlled by a two-component regulatory system composed of a histidine kinase sensor protein (PhoR) within the inner membrane and a transcriptional response regulator (PhoB/PhoR) on the cytoplasmic side of the membrane. These proteins bind to upstream promoters in the pho regulon in order to induce a general change in gene transcription. This occurs when the cell senses low concentrations of phosphate within its internal environment causing the response regulator to be phosphorylated inducing an overall decrease in gene transcription. This mechanism is ubiquitous within gram-positive, gram-negative, cyanobacteria, yeasts, and archaea. Signal transduction pathway Depletion of inorganic phosphate within the cell is required for activation of the Pho regulon in most prokaryotes. In the most commonly studied bacterium, E. coli, seven total proteins are used to detect intracellular levels of inorganic phosphate along with transfusing that signal appropriately. Of the seven proteins, one is a metal binding protein (PhoU) and four are phosphate-specific transporters (Pst S, Pst C, Pst A, and Pst B). The transcriptional response regulator PhoR activates PhoB when it senses low intracellular inorganic phosphate levels. Alternative phosphate usage Although inorganic phosphate is primarily used in the Pho regulon system, there are several species of bacteria that can utilize varying forms of phosphate. One example is seen in E. coli which can use both inorganic and organic phosphate, as well as naturally occurring or synthetic phosphates (Phn). Several enzymes breakdown the compounds of the alternative phosphates, allowing the organism to use the phosphate via the C-P lyase pathway. Other species of bacteria like Pseudomonas aeruginosa and Salmonella typhimurium use a different pathway called the phosphonatase pathway, whereas the bacterium Enterobacter aerogenes can use either one of the pathways to cleave the C-P bond found in the alternative phosphates. == Conservation among bacterial species ==

Although the Pho regulon system is most widely studied in Escherichia coli it is found in other bacterial species such as Pseudomonas fluorescens and Bacillus subtilis. In Pseudomonas fluorescens, the transcriptional response regulator (PhoB/PhoR) retain the same function they play in E. coli. Bacillus subtilis also shares some similarities when encountering low intracellular phosphate concentrations. Under phosphate-starved conditions B. subtilis binds its transcription regulator, PhoP and the histidine kinase, PhoR to the Pho-regulon gene which induces a production of teichuronic acid. Furthermore, recent studies have suggested the critical role that techoic acid plays in the cell wall of B. subtilis, by acting as a phosphate reservoir and storing the necessary amount of inorganic phosphate in phosphate-starved conditions. == The Pho regulon's effect on pathogenesis ==

Because bacteria use the Pho regulon to maintain homeostasis of Pi, it has the added effect of being used to control other genes. Many of the other genes activated or repressed by the Pho regulon cause virulence in bacterial pathogens. Three ways that this regulon effects virulence and pathogenicity are toxin production, biofilm formation, and acid tolerance. It could be activated by other signals in the environment, Synthesis of the Asr protein imparts acid shock resistance to E. coli enabling it to survive in environments like the stomach which has a low pH. Many acid tolerance genes are induced by more than just the low pH environment and require other environmental signals to be present in order to be activated. These specific nutrients being present or in low concentrations, anaerobiosis, and host-produced factors. ==References==