The synergistic effect of Nisin and food additives

As a natural antibacterial peptide derived from lactic acid bacteria, nisin primarily inhibits Gram-positive bacteria (such as Listeria, Staphylococcus aureus, and Bacillus). However, its limitations—including a narrow antibacterial spectrum and the need for high doses when used alone—lead to its frequent combined application with other food additives. Through the synergistic effect of "complementary mechanisms and superimposed actions," the combination can expand the antibacterial spectrum, reduce the dosage of single additives, enhance food preservation effects, and mitigate potential safety risks of chemical additives. The specific synergistic effects and application scenarios are categorized as follows:

I. Synergy with Chemical Preservatives: Expanding the Antibacterial Spectrum and Enhancing Inhibition of Gram-Negative Bacteria

When used alone, nisin struggles to penetrate the outer membrane of Gram-negative bacteria, resulting in weak inhibitory effects on E. coli, Salmonella, and Vibrio parahaemolyticus. However, combined use with chemical preservatives overcomes this limitation, forming a synergistic mechanism of "targeted attack + outer membrane disruption."

For example, when combined with organic acid preservatives (e.g., citric acid, lactic acid, acetic acid, sorbic acid), organic acids reduce the pH of the food system, disrupting the integrity of the Gram-negative bacterial outer membrane: the acidic environment denatures outer membrane proteins and loosens lipopolysaccharide structures, creating channels for nisin to penetrate the cell membrane. Additionally, the acidic environment enhances nisin’s inhibitory effect on Gram-positive bacterial spores, preventing spore germination. This synergistic combination is commonly used in chilled meat products (e.g., sausages) and acidic beverages (e.g., lactic acid bacteria drinks), controlling both Gram-positive bacterial contamination and Gram-negative bacterial spoilage and extending the shelf life by 2–3 times.

Another typical case is the combination of nisin and nitrite: while nitrite inhibits Clostridium botulinum, excessive use produces the carcinogen nitrosamine. Nisin, by contrast, exerts a strong direct inhibitory effect on Clostridium botulinum (a Gram-positive bacterium). Their combination reduces nitrite dosage by 30%–50%, ensuring food safety while minimizing nitrosamine formation. This is widely applied in cured meat products and canned meat products.

II. Synergy with Natural Plant-Derived Extracts: Strengthening Antibacterial Activity and Enhancing Natural Preservation Properties

Natural plant-derived extracts (e.g., carvacrol, cinnamaldehyde, eugenol, rosemary extract) exhibit broad-spectrum antibacterial activity (inhibiting both Gram-positive and Gram-negative bacteria). However, their antibacterial activity is unstable when used alone, as it is easily affected by the food system (e.g., fats, proteins). The peptide structure of nisin and the volatile components of plant extracts form "complementary action targets," significantly enhancing synergistic effects.

Taking carvacrol (the main component of oregano extract) as an example: carvacrol disrupts the fluidity of bacterial cell membranes, increasing membrane permeability; meanwhile, nisin, via its unique "lanthionine ring" structure, binds to phospholipids on the bacterial cell membrane, forming transmembrane channels that cause the leakage of intracellular nutrients such as potassium ions and amino acids. When acting together, the degree of cell membrane damage far exceeds that of single use—this not only rapidly kills Gram-positive bacteria but also strongly inhibits Gram-negative bacteria such as E. coli and Salmonella. This synergistic combination is used in fresh fruits and vegetables (e.g., strawberries, lettuce) and chilled dairy products (e.g., fresh milk): it avoids the use of chemical preservatives, improves consumer acceptance through the "natural ingredient + natural antibacterial peptide" combination, and extends the freshness period by 1–2 times.

Additionally, the combination of nisin and tea polyphenols offers dual synergy of "antibacterial + antioxidant": tea polyphenols scavenge free radicals in food, delaying fat oxidation and color deterioration, while nisin inhibits microbial reproduction. Together, they maintain the sensory quality and safety of food, and are commonly used in fried foods (e.g., potato chips) and nut products.

III. Synergy with Enzyme Preparations: Disrupting Bacterial Defense Mechanisms and Enhancing Inhibition of Persistent Bacteria

Certain enzyme preparations (e.g., lysozyme, glucose oxidase, lipase) assist nisin by degrading bacterial cell walls or altering the food microenvironment, with particularly significant effects on drug-resistant bacteria or spore-forming bacteria.

For instance, the combination of nisin and lysozyme: lysozyme specifically hydrolyzes the peptidoglycan in Gram-positive bacterial cell walls, causing wall damage; nisin then directly enters the cell through the damaged wall, acting on the cell membrane and cytoplasm to accelerate bacterial death. For difficult-to-kill Gram-positive bacterial spores (e.g., Bacillus subtilis spores), lysozyme also disrupts the spore cortex structure to inhibit germination, while nisin prevents further proliferation of germinated spores. Their synergy completely controls spore contamination and is applied in canned foods (e.g., mushroom cans) and baked goods (e.g., bread), avoiding issues such as "can swelling" and "mold growth" caused by incomplete heat sterilization.

Another example is the unique synergistic mechanism of nisin and glucose oxidase: glucose oxidase catalyzes the conversion of glucose in food into gluconic acid and hydrogen peroxide. Hydrogen peroxide has broad-spectrum antibacterial activity, assisting nisin in inhibiting Gram-negative bacteria; meanwhile, gluconic acid lowers the food pH, further enhancing nisin’s antibacterial activity. This combination is used in high-sugar foods (e.g., jam, honey): it utilizes the food’s own glucose as a "substrate" to generate antibacterial substances, controls microbial contamination through synergy, and reduces the addition of exogenous additives.

IV. Synergy with Physical Preservation Technologies: Reducing Treatment Intensity and Minimizing Food Quality Damage

Beyond combining with food additives, nisin is often used with physical preservation technologies (e.g., chilled storage, high-pressure processing (HPP), pulsed electric field processing). Through the synergy of "physical disruption + chemical inhibition," this reduces the intensity of physical treatment and minimizes damage to food nutrition and sensory quality.

In chilled storage, for example, low temperatures delay microbial growth but cannot completely inhibit psychrotolerant bacteria (e.g., Listeria). Nisin, however, specifically inhibits Listeria (a Gram-positive bacterium). Their combination allows the refrigeration temperature to be moderately increased from 0–4°C to 5–7°C (while still controlling microbes), reducing the impact of low temperatures on food texture (e.g., preventing fruit freezing damage and meat stiffness) and lowering refrigeration energy consumption.

In high-pressure processing (HPP), high pressure (300–600 MPa) disrupts bacterial cell membranes and protein structures but has limited effect on killing spore-forming bacteria. Nisin can penetrate the spore cortex after HPP treatment to inhibit spore germination. Their synergy reduces HPP intensity by 20%–30%, minimizing damage to food nutrients (e.g., vitamin C, B vitamins) while ensuring bactericidal efficacy. This is applied in cold-sterilized fruit juices and ready-to-eat seafood (e.g., salmon sashimi).