Regulation of the Phosphorelay and the Initiation of Sporulation in Bacillus Subtilis

The initiation of sporulation of bacteria is a complex cellular event controlled by an extensive network of regulatory proteins that serve to ensure that a cell embarks on this differentiation process only when appropriate conditions are met. The major signal-transduction pathway for the initiation of sporulation is the phosphorelay, which responds to environmental, cell cycle, and metabolic signals, and phosphorylates the Spo0A transcription factor activating its function. Signal input into the phosphorelay occurs through activation of kinases to phosphorylate a secondary-messenger protein, Spo0F. Spo0F-P serves as a substrate for phosphoprotein phosphotransferase, Spo0B, which phosphorylates Spo0A. The pathway is regulated by transcriptional control of its component proteins and by regulating phosphate flux through the pathway. This is accomplished by several regulatory proteins, and by activated Spo0A, which regulates transcription of genes for its own synthesis. Spo0A-P indirectly controls the transcription of numerous genes by regulating the level of other transcription regulators and directly activates the transcription of several regulatory proteins and sigma factors required for progression to the second stage of sporulation. Although the pathway and regulatory proteins have been identified, the signals and effectors for these regulators remain a mystery.