Peptide Antibiotic Sensing and Detoxification Modules ofBacillus subtilis

Abstract

ABSTRACTPeptide antibiotics are produced by a wide range of microorganisms. Most of them target the cell envelope, often by inhibiting cell wall synthesis. One of the resistance mechanisms against antimicrobial peptides is a detoxification module consisting of a two-component system and an ABC transporter. Upon the detection of such a compound, the two-component system induces the expression of the ABC transporter, which in turn removes the antibiotic from its site of action, mediating the resistance of the cell. Three such peptide antibiotic-sensing and detoxification modules are present inBacillus subtilis. Here we show that each of these modules responds to a number of peptides and confers resistance against them. BceRS-BceAB (BceRS-AB) responds to bacitracin, plectasin, mersacidin, and actagardine. YxdJK-LM is induced by a cationic antimicrobial peptide, LL-37. The PsdRS-AB (formerly YvcPQ-RS) system responds primarily to lipid II-binding lantibiotics such as nisin and gallidermin. We characterized thepsdRS-ABoperon and defined the regulatory sequences within the PpsdApromoter. Mutation analysis demonstrated that PpsdAexpression is fully PsdR dependent. The features of both the PbceAand PpsdApromoters make them promising candidates as novel whole-cell biosensors that can easily be adjusted for high-throughput screening.