Contributions of the σ W , σ M and σ X regulons to the lantibiotic resistome of B acillus subtilis

Summary In B acillus subtilis , the extracytoplasmic function ( ECF ) σ factors σ M , σ W and σ X all contribute to resistance against lantibiotics. Nisin, a model lantibiotic, has a dual mode of action: it inhibits cell wall synthesis by binding lipid II , and this complex also forms pores in the cytoplasmic membrane. These activities can be separated in a nisin hinge‐region variant ( N 20 P M 21 P ) that binds lipid II , but no longer permeabilizes membranes. The major contribution of σ M to nisin resistance is expression of ltaSa , encoding a stress‐activated lipoteichoic acid synthase, and σ X functions primarily by activation of the dlt operon controlling d ‐alanylation of teichoic acids. Together, σ M and σ X regulate cell envelope structure to decrease access of nisin to its lipid II target. In contrast, σ W is principally involved in protection against membrane permeabilization as it provides little protection against the nisin hinge region variant. σ W contributes to nisin resistance by regulation of a signal peptide peptidase ( SppA ), phage shock proteins ( PspA and YvlC , a PspC homologue) and tellurite resistance related proteins ( YceGHI ). These defensive mechanisms are also effective against other lantibiotics such as mersacidin, gallidermin and subtilin and comprise an important subset of the intrinsic antibiotic resistome of B . subtilis .