Nisin is a polycyclic antibacterial peptide classified as a lantibiotic, characterized by the presence of the unusual amino acids lanthionine and methyllanthionine. It was first discovered in 1928 in fermented milk cultures and is produced by certain strains of Lactococcus lactis. Its significance lies in its potent bactericidal activity against a broad spectrum of Gram-positive bacteria, including many foodborne pathogens and antibiotic-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA) and Listeria monocytogenes. Due to its safety and efficacy, nisin has been used globally as a food preservative (designated E234) for over 50 years, representing one of the most studied and commercially successful bacteriocins. More recently, its research applications have expanded into biomedical fields, exploring its potential in treating bacterial infections, cancer therapy, and biofilm disruption.
Quick Facts
| Also Known As | Nisin A, Nisin Z, Lantibiotic Nisin, E234 |
|---|---|
| Sequence | ITSISLCTPGCKTGALMGCNMKTATCHCSIHVSK |
| Molecular Formula | C143H230N42O37S7 |
| Molecular Weight | 3354.1 Da |
| PubChem CID | 16129667 |
Research Parameters
| Half-Life | Unknown for systemic administration in humans. In food matrices and in vitro, activity persists for extended periods depending on pH and temperature. |
|---|---|
| Stability | Lyophilized powder is stable for years when stored appropriately. In aqueous solution, stability is highly pH-dependent; it is most stable in acidic conditions (pH ~3.5) and loses activity rapidly above pH 7 and upon prolonged exposure to high temperatures. Reconstituted solutions for research are typically used immediately or stored short-term at 4°C. |
| Solubility | Soluble in dilute acidic aqueous solutions (e.g., 0.02 N HCl, 0.1% acetic acid). Poorly soluble in neutral or basic water. For research, it is often reconstituted in a mild acid like 0.02 N HCl or a buffered saline at low pH. |
| Vial Size | 10 mg |
| Storage (Lyophilized) | -20°C, protect from light and moisture. Stable for years under these conditions. |
| Storage (Reconstituted) | 2-8°C (refrigerated) for short-term storage (days to a week). For long-term stability, aliquoting and freezing at -20°C or -80°C is recommended, though repeated freeze-thaw cycles should be avoided. |
| Typical Research Dose | Not applicable for human use. In animal research, doses vary from 200-1000 mcg per animal for mice (approximately 10-50 mg/kg) depending on the route and study objective. |
| Cycle Parameters | Not applicable. Research protocols are highly variable based on the experimental model (e.g., single dose for acute infection, daily administration for 5-14 days in chronic models, or continuous exposure in in vitro studies). |
| Amino Acid Count | 34 |
Mechanism of Action
Nisin's primary mechanism involves pore formation in bacterial cell membranes, leading to rapid cell death. It initially binds to lipid II, an essential precursor for bacterial cell wall synthesis. This binding serves a dual purpose: it inhibits cell wall biosynthesis and recruits lipid II as a docking molecule to facilitate nisin's insertion into the cell membrane.
Membrane Pore Formation: Upon binding lipid II, nisin monomers oligomerize to form transient pores in the cytoplasmic membrane. This causes rapid efflux of essential ions (e.g., K+, H+), amino acids, and ATP, collapsing the proton motive force and leading to cell death.
Cell Wall Inhibition: By binding to lipid II, nisin sequesters this molecule, preventing its incorporation into the peptidoglycan layer. This inhibits the transglycosylation step of cell wall synthesis, weakening the bacterial cell envelope.
Biofilm Disruption: Nisin can penetrate and disrupt pre-formed biofilms by killing both actively growing and dormant cells within the biofilm matrix, making it effective against surface-associated bacterial communities that are typically resistant to conventional antibiotics.
Research Applications
Antimicrobial Applications: Nisin is extensively researched as a therapeutic agent against antibiotic-resistant bacteria. Studies demonstrate efficacy against MRSA, vancomycin-resistant enterococci (VRE), and Clostridium difficile. Its unique target (lipid II) and rapid bactericidal action make it a promising candidate for novel antimicrobial drugs, especially in topical formulations for skin and wound infections.
Oncology Research: Preliminary in vitro and in vivo studies indicate nisin may have selective cytotoxic effects on certain cancer cell lines, including head and neck squamous cell carcinoma and colon cancer. Proposed mechanisms include induction of apoptosis and cell cycle arrest, though this area remains exploratory.
Dental and Oral Health: Research investigates nisin's role in preventing dental caries and periodontal diseases by targeting cariogenic bacteria like Streptococcus mutans and periodontal pathogens. It is studied in mouthwashes, gels, and dental materials to control oral biofilms.
Food Safety and Biopreservation: While established as a food additive, ongoing research optimizes its use in active packaging, edible coatings, and combination treatments with other preservatives or physical methods to enhance food safety and shelf-life against spoilage and pathogenic bacteria.
Safety & Side Effects
Nisin has a long history of safe consumption as a food preservative and is generally recognized as safe (GRAS) by regulatory agencies for oral intake in food. In animal studies, it shows low systemic toxicity. High intravenous or intraperitoneal doses in rodents can cause transient hypotension and hemolysis due to its surfactant-like properties and potential interaction with mammalian membranes at very high concentrations. Anecdotal reports from its use as a food additive are virtually nonexistent, indicating excellent oral tolerance. Theoretical concerns include the potential for development of bacterial resistance, although this appears to be low and slow to emerge in laboratory settings. Allergic reactions are considered extremely rare.
Dosage Information
This information is derived from preclinical and in vitro research only. There is no established human therapeutic dosing protocol. In animal research, doses vary widely depending on the model and route. For antimicrobial studies in mice, intraperitoneal doses have ranged from 0.2 mg/kg to 10 mg/kg. Topical applications in wound models often use concentrations of 25-100 μg/mL in gels or solutions. Oral administration in gut infection models has used doses up to 50 mg/kg. Routes of administration in research include intraperitoneal, subcutaneous, oral gavage, and topical application. Frequency is typically once or twice daily, with study durations ranging from a single dose to several weeks.
References
Delves-Broughton, J., Blackburn, P., Evans, R.J., Hugenholtz, J. Applications of the bacteriocin, nisin. Antonie van Leeuwenhoek, 69, 193-202, 1996.
Cotter, P.D., Hill, C., Ross, R.P. Bacteriocins: developing innate immunity for food. Nature Reviews Microbiology, 3(10), 777-788, 2005.
Shin, J.M., Gwak, J.W., Kamarajan, P., Fenno, J.C., Rickard, A.H., Kapila, Y.L. Biomedical applications of nisin. Journal of Applied Microbiology, 120(6), 1449-1465, 2016.
Field, D., Begley, M., O'Connor, P.M., Daly, K.M., Hugenholtz, F., Cotter, P.D., Hill, C., Ross, R.P. Bioengineered nisin A derivatives with enhanced activity against both Gram positive and Gram negative pathogens. PLoS One, 7(10), e46884, 2012.
Joo, N.E., Ritchie, K., Kamarajan, P., Miao, D., Kapila, Y.L. Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1. Cancer Medicine, 1(3), 295-305, 2012.
Juturu, V., Wu, J.C. Microbial production of bacteriocins: Latest research development and applications. Biotechnology Advances, 36(8), 2187-2200, 2018.
Gharsallaoui, A., Oulahal, N., Joly, C., Degraeve, P. Nisin as a food preservative: Part 1: Physicochemical properties, antimicrobial activity, and main uses. Critical Reviews in Food Science and Nutrition, 56(8), 1262-1274, 2016.