PhoP-PhoQ is a two-component system that governs virulence, mediates the adaptation to Mg2+-limiting environments, and regulates numerous cellular activities in several gram-negative species. It consists of the inner membrane sensor PhoQ and the cytoplasmic regulator PhoP. The PhoP-PhoQ system is encoded by the phoP locus, which was first identified in Salmonella enterica serovar Typhimurium as controlling the expression of a nonspecific acid phosphatase (51). This is the reason for the pho in phoP, a designation typically denoting loci involved in phosphate metabolism. However, the PhoP-PhoQ system responds to the levels of Mg2+ and Ca2+ (29) and should not be confused with PhoB-PhoR or PhoP-PhoR, two-component systems governing the adaptation to phosphate-limiting conditions in Escherichia coli (83) and Bacillus subtilis (49), respectively. The realization that PhoP-PhoQ controls virulence in Salmonella (31, 58) promoted new interest in the system in the late 1980s and has rendered the PhoP regulon one of the best characterized regulons in enteric bacteria.
Here, I first discuss how the PhoP-PhoQ two-component system responds to environmental cues and interacts with other regulatory systems to integrate multiple signals into a coordinated cellular response and then I describe the PhoP-regulated genes mediating the various PhoP-controlled functions, including virulence. The Salmonella-centric tone of this review reflects the fact that most of the work on PhoP-PhoQ has been carried out with this enteric pathogen. However, many of the findings discussed about Salmonella PhoP-PhoQ apply to PhoP-PhoQ homologues in other gram-negative species. A model of the PhoP-PhoQ system is presented in Fig. Fig.1,1, and the genes and cellular activities regulated by Phop-PhoQ in Salmonella are listed in Table Table1.1.