Contributions of ATP, GTP, and redox state to nutritional stress activation of the Bacillus subtilis σ^B transcription factor

The general stress regulon of Bacillus subtilis is induced by activation of the σ^B transcription factor. σ^B activation occurs when one of two phosphatases responds to physical or nutritional stress to activate a positive σ^B regulator by dephosphorylation. The signal that triggers the nutritional stress phosphatase (RsbP) is unknown; however, RsbP activation occurs under culture conditions (glucose/phosphate starvation, azide or decoyinine treatment) that reduce the cell's levels of ATP and/or GTP. Variances in nucleotide levels in these instances may be coincidental rather than causal. RsbP carries a domain (PAS) that in some regulatory systems can respond directly to changes in electron transport, proton motive force, or redox potential, changes that typically precede shifts in high-energy nucleotide levels. The current work uses Bacillus subtilis with mutations in the oxidative phosphorylation and purine nucleotide biosynthetic pathways in conjunction with metabolic inhibitors to better define the inducing signal for RsbP activation. The data argue that a drop in ATP, rather than changes in GTP, proton motive force, or redox state, is the key to triggering σ^B activation.