Deciphering a complex genetic regulatory network: the Bacillus subtilis sigmaW protein and intrinsic resistance to antimicrobial compounds.

Bacillus subtilis, a spore-forming soil bacterium, is the preeminent model system for the analysis of gene regulation in Gram-positive bacteria. Early genetic analyses established that this organism uses alternative sigma (sigma) subunits to reprogram RNA polymerase to activate genes required for growth phase transitions, motility, general stress response, and sporulation. Unexpectedly, the genome sequence predicts the presence of an additional seven a subunits: all members of the extracytoplasmic function (ECF) a subfamily of regulators that typically respond to cell envelope stresses. Here, we review our current understanding of one of these a factors, sigmaW, with an emphasis on experimental strategies and approaches. Exposure to cell envelope active antibiotics and toxic peptides triggers a signaling cascade that releases sigmaW from its cognate anti-sigma thereby allowing transcription of approximately 60 sigmaW-dependent genes. These genes encode proteins that inactivate, sequester, or eliminate toxic compounds from the cell.