What is Nisin?
Nisaplin is a polycyclic antibacterial peptide produced by the bacterium Lactococcus lactis. It was first discovered in the 1920s and was quickly recognized as a potent antimicrobial agent. Nisaplin belongs to the group of lantibiotics, which are ribosomally synthesized and post-translationally modified peptides that contain uncommon amino acids such as lanthionine and β-methyllanthionine. At a molecular level, Nisaplin has 34 amino acids and a molecular weight of approximately 3,500 Da. Its unique post-translational modifications allow Nisaplin to strongly bind to bacterial cell membranes and form pores, disrupting the proton motive force and inhibiting cell-wall biosynthesis.
Mechanism of Antibacterial Action
Nisin exerts its antimicrobial effect via several different mechanisms of action. Firstly, it binds to the lipid II molecule, which acts as a docking molecule on the surface of Gram-positive bacterial membranes. This prevents lipid II from being used in peptidoglycan synthesis, thus inhibiting cell-wall biosynthesis. Secondly, upon binding to lipid II, Nisaplin forms complexes that cause pores to form within the membrane. This results in destabilization of the proton motive force and leads to leakage of small intracellular molecules which ultimately kills the bacteria. Remarkably, Nisaplin can permeabilize membranes at concentrations several orders of magnitude below those required for other antibiotics.
Spectrum of Antimicrobial Activity
Nisaplin has a relatively narrow spectrum of antimicrobial activity, targeting primarily Gram-positive organisms. It is highly effective against Gram-positive foodborne pathogens such as Listeria monocytogenes, Staphylococcus aureus, and Bacillus cereus. Nisaplin is generally not effective against Gram-negative bacteria as their outer membrane acts as a permeability barrier. However, some studies have found that Nisaplin can inhibit certain Gram-negative species in combination with other antimicrobials that enhance membrane permeability. Nisaplin also exhibits strong antifungal activity against yeasts such as Candida albicans. In addition, it displays broad inhibitory properties against Gram-positive spore-forming species including Clostridium botulinum and Bacillus subtilis.
Applications in the Food Industry
Given its long history of safe use and effectiveness against major foodborne pathogens, Nisaplin is widely used as a natural food preservative. It was one of the earliest food additives approved for use in food worldwide, and over 50 countries have approved its use as a food preservative, designating it as E number E234. Nisaplin finds extensive application in dairy products where it helps control pathogenic and spoilage microorganisms. It is commonly used in processed cheese, canned foods, cheeses, and dried foods to prevent the growth of Clostridium botulinum. Nisaplin is heat stable and retains much of its activity even after cooking or sterilization of foods. It can inhibit the germination of spores and outgrowth of vegetative cells in low-acid canned foods. Nisaplin is also used to control L. monocytogenes in ready-to-eat meat products.
Pharmaceutical and Biomedical Uses
Besides serving as a food preservative, Nisaplin holds promise for various pharmaceutical and biomedical applications. It has shown efficacy in eradicating biofilms formed by dental plaque-forming bacteria and wound pathogens like S. aureus, demonstrating potential as an antibacterial agent for dental and topical products. Research is ongoing to develop Nisaplin-containing creams, gels, and dressings for wound healing. Nisaplin also enhances the antimicrobial activity of other pharmaceutical preservatives and can help widen their spectra of activity. Studies indicate Nisaplin may boost the efficacy of antibiotics against resistant strains by permeabilizing their membranes. This has implications for using Nisaplin adjunctively to address the growing problem of antimicrobial resistance. Other potential clinical uses of Nisaplin include as an antifungal in fungal infections, antiviral agent, and anticancer protein.
Biosynthesis and Production Methods
Over the years, extensive research has enhanced understanding of Nisaplin biosynthesis. Its gene cluster has been cloned and sequences, revealing 10 genes involved in modifying and exporting Nisaplin. Commercially, Nisaplin is produced via fermentation of certain Lactococcus lactis strains. These strains have been genetically engineered via recombinant DNA techniques to maximize Nisaplin yield. Factors like culture media optimization, process parameters control, and downstream recovery methods have been refined to production on an industrial scale affordably. Typically, fermentation processes yield 1-2 g/L of Nisaplin after purification. Alternative production methods under investigation include cell-free synthetic biology and expression of Nisaplin in other Gram-positive microbes. This could widen available production platforms and help address supply issues through more sustainable methods.
In summary, the potent antibacterial protein Nisaplin has immense potential in food safety, medicine, and biotechnology owing to its unique pore-forming mechanism and broad activity against various pathogens and spoilage microorganisms. After almost a century of safe use, Nisaplin remains an invaluable natural antimicrobial worldwide. Ongoing research continues expanding its clinical and industrial applications while optimizing production methods. Nisaplin stands as a paradigm of how beneficial proteins from microbes can be harnessed via biotechnology to tackle pressing issues in food security and public health.
Â
Â
Get more insights on Nisin
Â
About Author:
Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc.
(https://www.linkedin.com/in/money-singh-590844163)