Nisin

Overview

Nisin contains unusual post-translationally modified residues, including dehydroalanine, dehydrobutyrine and five thioether-bridged lanthionine rings, which give it a rigid structure and resistance to degradation. First used to control Clostridium spoilage in cheese in the 1950s, it became the first bacteriocin in broad commercial application and is generally recognised as safe.

Beyond food, nisin has drawn interest as a therapeutic candidate. It is active against clinically important Gram-positive pathogens including methicillin-resistant Staphylococcus aureus, streptococci, enterococci and Clostridioides difficile, and a low propensity for resistance (Shin et al.). Investigational uses include oral care, mastitis, wound and skin infections, and it has been explored as an anticancer agent in preclinical models.

Nisin's main limitations for systemic therapy are reduced stability at neutral-to-alkaline pH and cationic-peptide-related cytotoxicity at higher concentrations, which have kept its human use largely confined to food, topical and mucosal applications.

Mechanism of Action

The N-terminal lanthionine rings of nisin recognise the pyrophosphate cage of lipid II with high affinity, sequestering this essential cell-wall building block. Beyond inhibiting transglycosylation, nisin-lipid II complexes oligomerise so that the flexible C-terminal region spans the membrane, forming stable, targeted pores. This dual mechanism accounts for its potency and the low frequency of spontaneous resistance.