RelA Is a Component of the Nutritional Stress Activation Pathway of theBacillus subtilisTranscription Factor σB

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Abstract
The general stress regulon of Bacillus subtilis is induced by the activation of the σB transcription factor. Activation of σB occurs when one of two phosphatases (RsbU and RsbP), each responding to a unique type of stress, actuates a positive regulator of σB by dephosphorylation. Nutritional stress triggers the RsbP phosphatase. The mechanism by which RsbP becomes active is unknown; however, its activation coincides with culture conditions that are likely to reduce the cell's levels of high-energy nucleotides. We now present evidence that RelA, a (p)ppGpp synthetase and the key enzyme of the stringent response, plays a role in nutritional stress activation of σB. An insertion mutation that disrupts relA blocks the activation of σB in response to PO4 or glucose limitation and inhibits the drop in ATP/GTP levels that normally accompanies σB induction under these conditions. In contrast, the activation of σB by physical stress (e.g., ethanol treatment) is not affected by the loss of RelA. RelA's role in σB activation appears to be distinct from its participation in the stringent response. Amino acid analogs which induce the stringent response and RelA-dependent (p)ppGpp synthesis do not trigger σB activity. In addition, neither a missense mutation in relA (relA240GE) nor a null mutation in rplK (rplK54), either of which is sufficient to inhibit the stringent response and RelA-dependent (p)ppGpp synthesis, fails to block σB activation by PO4 or glucose limitation.