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 ha em A biosynthesis, and it is required for anaerobic respiration in this org anism. We reported previously that the operon encoding these regulatory pro teins, the resABCDE operon, is induced under several conditions, one of whi ch is phosphate starvation. We report here that this transcription requires the PhoP-PhoR two-component system, whereas other induction conditions do not. The PhoP similar to P response regulator directly binds to and is esse ntial for transcriptional activation of the resABCDE operon as well as bein g involved in repression of the internal resDE promoter during phosphate-li mited growth. The concentration of ResD in various phoP mutant strains corr oborates the role of PhoP in the production of ResD. These interactions res ult in a regulatory network that ties together the cellular functions of re spiration/energy production and phosphate starvation. Significantly, this r epresents the first evidence for direct involvement of one two-component sy stem in transcription of a second two-component system.