PhoP-PhoQ: Difference between revisions
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'''PhoP-PhoQ''' is a two component regulatory system found in some gram-negative bacteria such as ''Escherichia coli''[http://en.wikipedia.org/wiki/Escherichia_coli], ''Salmonella enterica''[http://en.wikipedia.org/wiki/Salmonella_enterica], and ''Yersinia pestis''[http://en.wikipedia.org/wiki/Yersinia_pestis]. In a classic two component regulatory system, there exists a sensor kinase and a response regulator<ref name=Hoch>PMID:10745001</ref>. In the phoP-phoQ system, phoQ acts as the sensor kinase and phoP acts as the response regulator. The purpose of this signal transduction system in bacteria is to modify cellular output in response to environmental signals. In response to particular environmental stimuli, such as a low [Mg<sup>2+</sup>], the sensor kinase, phoQ autophosphorylates. Phosphorylated phoQ then transphosphorylates the response regulator, phoP, which in turn binds DNA and modulates transcription.<ref name=Hoch>PMID:10745001</ref> | '''PhoP-PhoQ''' is a two component regulatory system found in some gram-negative bacteria such as ''Escherichia coli''[http://en.wikipedia.org/wiki/Escherichia_coli], ''Salmonella enterica'' Typhi[http://en.wikipedia.org/wiki/Salmonella_enterica], and ''Yersinia pestis''[http://en.wikipedia.org/wiki/Yersinia_pestis]. In a classic two component regulatory system, there exists a sensor kinase and a response regulator<ref name=Hoch>PMID:10745001</ref>. In the phoP-phoQ system, phoQ acts as the sensor kinase and phoP acts as the response regulator. The purpose of this signal transduction system in bacteria is to modify cellular output in response to environmental signals. In response to particular environmental stimuli, such as a low [Mg<sup>2+</sup>], the sensor kinase, phoQ autophosphorylates. Phosphorylated phoQ then transphosphorylates the response regulator, phoP, which in turn binds DNA and modulates transcription.<ref name=Hoch>PMID:10745001</ref> | ||
<StructureSection load='2pl1' size='500' side='right' caption='BeF activated PhoP domain of E. Coli (PDB entry [[2pl1]])' scene=''> | <StructureSection load='2pl1' size='500' side='right' caption='BeF activated PhoP domain of E. Coli (PDB entry [[2pl1]])' scene=''> | ||
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Pathogenic bacteria seldom express virulence genes constitutively, they instead need to be able to express the correct virulence genes in the correct environment. Not all virulence factors confer a selective advantage to the microbe at the same stage of infection. Thus, it is the job of the phoP-phoQ system to modulate virulence gene expression according to the cellular micro-environment.<ref name=Hoch>PMID:10745001</ref> | Pathogenic bacteria seldom express virulence genes constitutively, they instead need to be able to express the correct virulence genes in the correct environment. Not all virulence factors confer a selective advantage to the microbe at the same stage of infection. Thus, it is the job of the phoP-phoQ system to modulate virulence gene expression according to the cellular micro-environment.<ref name=Hoch>PMID:10745001</ref> | ||
A particular and well studied | A particular and well studied example of this is the role of [Mg<sup>2+</sup.] in ''Salmonella enterica'' Typhi virulence. In response to low [Mg<sup>2+</sup>], such as would be found inside a macrophage phagosome, phoQ autophosphorylates and transphorphorylates phoP. PhoP then binds to the bacterial DNA and simultaneously activates the expression of pags (phoP activated genes) and represses the expression of prgs (phoP repressed genes). Among the gene products of pags are proteins necessary to survive inside the macrophage, a critical stage of ''Salmonella enterica'' Typphi pathogenesis. Among the gene products of prgs are proteins necessary for invasion and infection of the host, which are less important once in a host macrophage's phagosome. | ||
Two component regulatory systems such as phoP-phoQ are obviously an attractive target for future antimicrobial drugs. If the phoP-phoQ can be altered to a dysfunctional state, the relevant bacteria would have decreased pathogenicity and increased suceptibility to nonspecific immune defense. | Two component regulatory systems such as phoP-phoQ are obviously an attractive target for future antimicrobial drugs. If the phoP-phoQ can be altered to a dysfunctional state, the relevant bacteria would have decreased pathogenicity and increased suceptibility to nonspecific immune defense. | ||