AUTOREGULATION OF NISIN BIOSYNTHESIS IN LACTOCOCCUS-LACTIS BY SIGNAL-TRANSDUCTION

The post-translationally modified, antimicrobial peptide nisin is secr eted by strains of Lactococcus lactis that contain the chromosomally l ocated nisin biosynthetic gene cluster nisABTCIPRKFEG. When a 4-base p air deletion is introduced into the structural nisA gene (Delta nisA), transcription of Delta nisA is abolished. Transcription of the Delta nisA gene is restored by adding subinhibitory amounts of nisin, nisin mutants, or nisin analogs to the culture medium, but not by the unmodi fied precursor peptide or by several other antimicrobial peptides, Upo n disruption of the nisK gene, which encodes a putative sensor protein that belongs to the class of two-component regulators, transcription of Delta nisA was no longer inducible by nisin, Fusion of a nisA promo ter fragment to the promoterless reporter gene gusA resulted in expres sion of gusA in L, lactis NZ9800 (Delta nisA) only upon induction with nisin species, The expression level of gusA was directly related to t he amount of inducer that was added extracellularly, These results pro vide insight into a new mechanism of autoregulation through signal tra nsduction in prokaryotes and demonstrate that antimicrobial peptides c an exert a second function as signaling molecules.