Membrane-associated proteins encoded by the nisin gene cluster may function as a receptor for the lantibiotic...

Carnocin UI49, a lantibiotic produced by Carnobacterium piscicola shows bactericidal activity against many lactic acid bacteria. This paper describes the results of a study on the mode of action of carnocin UI49. It has previously been observed that nisin-producing Lactococcus lactis subsp. lactis strains are at least 10-fold more sensitive to carnocin UI49 relative to other lactic acid bacteria. Addition of carnocin UI49 to cells of L. lactis subsp. lactis NZ9700 resulted in a dissipation of the membrane potential and a rapid hydrolysis of internal ATP. These results suggest that carnocin UI49 may act at the cytoplasmic membrane. The correlation between production of and/or immunity to nisin and sensitivity to carnocin of L. lactis subsp. lactis strains was further investigated. Several transformed L. lactis subsp. lactis strains carrying a fragment of the nisin gene cluster were tested for their sensitivity to carnocin UI49 and their immunity to nisin. The results suggest that NisP, which is one of the membrane-associated proteins involved in the production of nisin acts as receptor for carnocin UI49. This may facilitate the binding and/or insertion of carnocin UI49 into the cytoplasmic membrane thus increasing its bactericidal activity. Lantibiotic-producing and non-producing mutants of Staphylococcus epidermidis and Lactobacillus sake did not show a difference in sensitivity to carnocin UI49. The proposed receptor-mediated action of carnocin UI49 at the cytoplasmic membrane therefore seems to be specific for the nisin-producing strains.