Pho signal transduction network reveals direct transcriptional regulation of one two-component system by another two-component regulator: Bacillus subtilis PhoP directly regulates production of ResD

The Bacillus subtilis ResD-ResE two-component system is responsible for the regulation of a number of genes involved in cytochrome c biogenesis and haem A biosynthesis, and it is required for anaerobic respiration in this organism. We reported previously that the operon encoding these regulatory proteins, the resABCDE operon, is induced under several conditions, one of which is phosphate starvation. We report here that this transcription requires the PhoP-PhoR two-component system, whereas other induction conditions do not. The PhoP~P response regulator directly binds to and is essential for transcriptional activation of the resABCDE operon as well as being involved in repression of the internal resDE promoter during phosphate-limited growth. The concentration of ResD in various phoP mutant strains corroborates the role of PhoP in the production of ResD. These interactions result in a regulatory network that ties together the cellular functions of respiration/energy production and phosphate starvation. Significantly, this represents the first evidence for direct involvement of one two-component system in transcription of a second two-component system.