The PhoQ/PhoP Regulatory Network of Salmonella Enterica

The PhoQ/PhoP two-component regulatory system is a major regulator of virulence in the enteric pathogen Salmonella enterica serovar Typhimurium. It also controls the adaptation to low Mg2+ environments by governing the expression and/or activity of Mg2+ transporters and of enzymes modifying the Mg2+-binding sites on the bacterial cell surface. The regulator PhoP modifies expression of approximately 3% of the Salmonella genes in response to the periplasmic Mg2+ concentration detected by the PhoQ protein. Genes that are directly controlled by the PhoP protein often differ in their promoter structures, resulting in distinct expression levels and kinetics in response to the low Mg2+ inducing signal. PhoP regulates a large number of genes indirectly: via other transcription factors and two-component systems that form a panoply of regulatory architectures including transcriptional cascades, feedforward loops and the use of connector proteins that modify the activity of response regulators. These architectures confer distinct expression properties that may be important contributors to Salmonella's lifestyle.