Extracytoplasmic function sigma factors with overlapping promoter specificity regulate sublancin production in...

Bacillus subtilis harbors seven extracytoplasmic function (ECF) sigma factors. At least three ECF sigma factors (sigma(M), sigma(W), and sigma(X)) are induced by, and provide resistance to, antibiotics and other agents eliciting cell envelope stress. Here, we report that ECF sigma factors also contribute to antibiotic production. B. subtilis 168 strains that are lysogenic for the SPbeta bacteriophage produce sublancin, which inhibits the growth of other, nonlysogenic strains. Genetic studies demonstrate that synthesis of sublancin is largely dependent on sigma(X), with a smaller contribution from sigma(M). A sigM sigX double mutant is unable to produce sublancin. This defect is primarily due to the fact that the sublancin biosynthesis is positively activated by the transition state regulator and AbrB paralog Abh, which counteracts transcriptional repression of the sublancin biosynthesis operon by AbrB. Ectopic expression of abh bypasses the requirement for sigma(M) or sigma(X) in sublancin synthesis, as does an abrB mutation. In addition to their major role in regulating sublancin expression by activating abh transcription, sigma(X) and sigma(M) also have a second role as positive regulators of sublancin expression that is independent of AbrB and Abh. Since sublancin resistance in nonlysogens is largely dependent on sigma(W), ECF sigma factors control both sublancin production and resistance.