Nisin: Application, Mechanism of action and Side effects

Application of Nisin

Nisin is a food preservative with a good food safety profile. It belongs to the group of natural polycyclic antimicrobial peptides produced by the fermentation of Lactococcus lactis bacteria and has potent activity against Gram-positive bacteria. It is commercially available in a number of variants such as nisin A, nisin E, nisin G, nisin H and nisin Z. Nisin is used as a natural preservative in a wide range of food products (including dairy, meat and wine), where it has antimicrobial properties that extend the shelf life of the product, and is also used in cosmetic and pharmaceutical products. In the European Union (EU) it is named E234.

Nisin is also widely used in biomedical applications. Studies have reported that nisin can prevent the growth of drug-resistant bacterial strains, such as methicillin resistant Staphylococcus aureus, Streptococcus pneumoniae, Enterococci and Clostridium difficile. Nisin has now been shown to have antimicrobial activity against both Gram-positive and Gram-negative disease-associated pathogens. Nisin has been reported to have anti-biofilm properties and can work synergistically in combination with conventional therapeutic drugs. In addition, like host defense peptides, nisin may activate the adaptive immune response and have an immunomodulatory role. Increasing evidence indicates that nisin can influence the growth of tumors and exhibit selective cytotoxicity towards cancer cells.

Several other reports on Nisin and oral health have found Nisin to be a potential oral antimicrobial agent. Nisin-based antimicrobial mouthwashes have shown promising clinical results in preventing plaque build-up and gingival inflammation in Beagles. Nisin A also inhibits the growth of cariogenic bacteria, including Streptococcus pyogenes, Streptococcus sanguinis, Streptococcus sobrinus and Streptococcus gordonii.

Mechanism of action

The antibacterial mechanism of Nisin is to inhibit bacterial growth by creating pores in the cell membrane and interfering with cell wall biosynthesis through specific lipid II interactions.At high concentrations of nisin, its interaction with phospholipids deforms bacterial cell membranes even when the lipid-II content is significantly different. Membrane thinning, destabilisation and reduction of lipid density depend on the degree of oligomerisation of nisin. Growth kinetics of Bacillus subtilis and Escherichia coli interestingly show recovery by extended lag phase under low concentrations of nisin treatment while high concentrations of nisin caused decrease in cell viability as recorded by striking reduction in membrane potential and surface area. The significant changes in the dipole potential and fluorescence anisotropy were observed in negatively charged membranes in the absence of lipid-II with increasing concentration of nisin. The identical correlation of cell viability, membrane potential dissipation and morphology with the concentration regime of nisin, in both Bacillus subtilis (lipid II rich) and Escherichia coli (lipid II impoverished), hints at a non-specific physical mechanism where degree of membrane deformation depends on degree of crowding and oligomerization of nisin.

Side effects

Generally recognized as safe (GRAS) is an American Food and Drug Administration (FDA) designation that a chemical or substance added to food is considered safe by experts, and so is exempted from the usual Federal Food, Drug, and Cosmetic Act (FFDCA) food additive tolerance requirements. Nisin (E234）is considered safe by FDA.

nisin (E234 ) is a very safe and effective supplement in most cases, but some mild side effects such as itching, nausea and flushing may occur. Other possible side effects include itching, rash, and vomiting.

References:

[1] SHEENA WEE . The detection, characterization, and quantification of dominant degradation products of nisin A and Z in selected dairy products by liquid chromatography–high-resolution mass spectrometry technique[J]. JDS communications, 2024. DOI:10.3168/jdsc.2023-0392.

[2] J.M. SHIN. Biomedical applications of nisin[J]. Journal of Applied Microbiology, 2015. DOI:10.1111/jam.13033.