Biomedical applications of nisin

Abstract

Nisin is a bacteriocin produced by a group of Gram-positive bacteria that belongs to Lactococcus and Streptococcus species. Nisin is classified as a Type A (I) lantibiotic that is synthesized from mRNA and the translated peptide contains several unusual amino acids due to post-translational modifications. Over the past few decades, nisin has been used widely as a food biopreservative. Since then, many natural and genetically modified variants of nisin have been identified and studied for their unique antimicrobial properties. Nisin is FDA approved and generally regarded as a safe peptide with recognized potential for clinical use. Over the past two decades the application of nisin has been extended to biomedical fields. 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-defence peptides, nisin may activate the adaptive immune response and have an immunomodulatory role. Increasing evidence indicates that nisin can influence the growth of tumours and exhibit selective cytotoxicity towards cancer cells. Collectively, the application of nisin has advanced beyond its role as a food biopreservative. Thus, this review will describe and compare studies on nisin and provide insight into its future biomedical applications.

Keywords: antimicrobial peptide; biofilm; cancer; infectious disease; lantibiotic; nisin; oral disease.

Figure 1. Timeline of Nisin Development

Figure 2. Peptide Structure of Nisin

Modified amino acids are colored gray with black letters. Dha, dehydroalanine (from Alanine); Dhb, dehydrobutyrine (from Threonine); Ala-S-Ala, lanthionine; Abu-S-Ala; β-methyllanthionine. The hinge region is composed of Asparagine-Methionine-Lysine. Arrows indicate the sites of amino acid substitutions for natural variants.

Figure 3. Nisin inhibits the formation of multi-species biofilms in a Bioflux controlled flow microfluidic model system

Cell containing saliva was added, then fed filter sterilized cell free saliva for 20–22 h at 37°C with or without nisin. Confocal microscopy images are represented in the x–y plane. A green signal indicates viable live cells (Syto 9) and a red signal indicates damaged/dead cells (propidium iodide). These images were previously published (Shin et al., 2015).

Figure 4. Nisin Z inhibits orasphere formation in HNSCC cells

Phase contrast images of oraspheres in HNSCC cells (UM-SCC-17B) cultured under suspension conditions and treated with control media or media containing nisin Z (100 to 800 μg/ml) for 36 h. These images were previously published (Kamarajan et al., 2015).