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Sigma B (σB ) is an alternative sigma factor that regulates the general stress response inBacillus subtilis and in many other Gram-positive organisms. σB activity inB. subtilis is tightly regulated via at least three distinct pathways within a complex signal transduction cascade in response to a variety of stresses, including environmental stress, energy stress, and growth at high or low temperatures. We probed the ability of fluoro-phenyl-styrene-sulfonamide (FPSS), a small-molecule inhibitor of σB activity inListeria monocytogenes , to inhibit σB activity inB. subtilis through perturbation of signal transduction cascades under various stress conditions. FPSS inhibited the activation of σB in response to multiple categories of stress known to induce σB activity inB. subtilis . Specifically, FPSS prevented the induction of σB activity in response to energy stress, including entry into stationary phase, phosphate limitation, and azide stress. FPSS also inhibited chill induction of σB activity in a ΔrsbV strain, suggesting that FPSS does not exclusively target the RsbU and RsbP phosphatases or the anti–anti-sigma factor RsbV, all of which contribute to posttranslational regulation of σB activity. Genetic and biochemical experiments, including artificial induction of σB , analysis of the phosphorylation state of the anti–anti-sigma factor RsbV, andin vitro transcription assays, indicate that while FPSS does not bind directly to σB to inhibit activity, it appears to prevent the release ofB. subtilis σB from its anti-sigma factor RsbW.

journal of bacteriology

Fluoro-Phenyl-Styrene-Sulfonamide, a Novel Inhibitor of σ<sup>B</sup>Activity, Prevents the Activation of σ<sup>B</sup>by Environmental and Energy Stresses in Bacillus subtilis

Fluoro-Phenyl-Styrene-Sulfonamide, a Novel Inhibitor of σBActivity, Prevents the Activation of σBby Environmental and Energy Stresses in Bacillus subtilis

Fluoro-Phenyl-Styrene-Sulfonamide, a Novel Inhibitor of σ^BActivity, Prevents the Activation of σ^Bby Environmental and Energy Stresses in Bacillus subtilis