Adverse effect of nisin resistance protein on nisin-induced expression system in Lactococcus lactis

Nisin is a bacteriocin that is widely used as a safe, natural preservative in food products. Nisin-controlled gene expression (NICE) systems and food-grade expression systems with nisin resistance as the selection marker are increasingly attracting attention owing to their food-grade statuses. However, the putative influence of nisin resistance on NICE systems deserves consideration when nisin is used as both the inducer and selection agent in lactococcal strains. In this paper, we described the cloning of the nisin resistance gene (nsr) and studied the effect of the encoded nisin resistance protein (NSR) on the efficiency of the NICE system in Lactococcus lactis, with the green fluorescence protein as the reporter protein. Results showed that NSR expression significantly weakened the inducing activity of nisin. Further studies have confirmed that this reduction in the inducing activity of nisin was a consequence of the proteolytic activity of NSR against nisin; the digested products showed drastically decreased inducing activities than native nisin. Conclusively, the expression of NSR imposes an adverse effect on the NICE system in L. lactis.