Mutations in multidrug efflux homologs, sugar isomerases, and antimicrobial biosynthesis genes differentially elevate activity of the sigma(X) and sigma(W) factors in Bacillus subtilis

The sigma(X) and sigma(W) extracytoplasmic function sigma factors regulate more than 40 genes in Bacillus subtilis. sigma(W) activates genes which fun ction in detoxification and the production of antimicrobial compounds, whil e aX activates functions that modify the cell envelope. Transposon mutagene sis was used to identify loci which negatively regulate sigma(W) or sigma(X ) as judged by up-regulation from the autoregulatory promoter site P-W or P -X. Fourteen insertions that activate P-W were identified. The largest clas s of insertions are likely to affect transport. These include insertions in genes encoding two multidrug efflux protein homologs (yqgE and yulE), a co mponent of the oligopeptide uptake system (oppA), and two transmembrane pro teins with weak similarity to transporters (yhdP and yueF). Expression from P-W is also elevated as a result of inactivation of at least one member of the sigma(W) regulon (ysdB), an ArsR homolog (yvbA), a predicted rhamnose isomerase (yulE), and a gene (pksR) implicated in synthesis of diffcidin, a polyketide antibiotic. In a parallel screen, we identified seven insertion s that up-regulate P-X, Remarkably, these insertions were in functionally s imilar genes, including a multidrug efflux homolog (yitG), a mannose-6-phos phate isomerase gene (yjdE), and loci involved in antibiotic synthesis (srf AB and possibly yogA and yngK). Significantly, most insertions that activat e P-W have little or no effect on P-X, and conversely, insertions that acti vate P-X have no effect on P-W. This suggests that these two regulons respo nd to distinct sets of molecular signals which may include toxic molecules which are exported, cell density signals, and antimicrobial compounds.