The synergistic mechanism of Nisin (nisin) combined with natural preservatives is mainly based on the collaborative complementarity of multiple action targets, achieving enhanced antibacterial effects through multiple mechanisms such as disrupting microbial physiological structures, interfering with metabolic pathways, and enhancing membrane permeability. The details are as follows:
I. Collaborative Complementarity of Action Targets
1. Synergy in Damaging Cell Walls and Membranes
Nisin can specifically bind to lipid II on the bacterial cell membrane, inserting into the membrane to form pores and causing intracellular substance leakage. Some natural preservatives (such as tea polyphenols and chitosan) weaken the bacterial protective barrier by chelating metal ions or interfering with cell wall synthesis. For example, chitosan can bind to peptidoglycan in the bacterial cell wall to increase its permeability. Collaborating with Nisin's membrane-damaging effect, this makes microorganisms more susceptible to death due to intracellular component loss.
2. Cross Inhibition of Metabolic Pathways
Nisin mainly inhibits cell wall synthesis in Gram-positive bacteria, while natural preservatives such as organic acids (citric acid, lactic acid) can inhibit microbial enzyme activity and ATP synthesis by lowering the environmental pH. After penetrating the cell membrane, the dissociated acid radicals interfere with intracellular acid-base balance. When the two are combined, nisin damages the cell membrane, allowing organic acids to more easily enter the cell and exert their effects, forming a dual strike of "membrane damage-metabolic inhibition".
II. Enhanced Effect on Membrane Permeability
1. Synergy of Nisin and Phenolic Substances in Membrane Damage
Natural phenolic substances such as tea polyphenols and rosemary extract are lipophilic and can insert into the lipid bilayer of the microbial cell membrane to destroy its integrity. Nisin increases membrane permeability by forming pores, while phenolic substances further expand the range of membrane damage, causing leakage or inactivation of key intracellular enzymes (such as respiratory chain enzymes and ATP enzymes). For example, when combined with tea polyphenols, Nisin opens membrane channels, and tea polyphenols consume reducing substances in the membrane through antioxidant effects, accelerating membrane structure collapse and significantly reducing microbial drug resistance.
2. Auxiliary Penetration of Polysaccharides
As a cationic polysaccharide, chitosan can bind to anionic groups (such as lipopolysaccharides) on the surface of the bacterial cell membrane, disrupting the membrane potential and forming transient channels. When nisin is combined with chitosan, chitosan first adsorbs to the bacterial surface through charge interactions, promoting more efficient binding of nisin to lipid II and enhancing membrane perforation efficiency, increasing antibacterial activity by several times compared to single use.
III. Synergy Between Antioxidation and Antibacterial Effects
1. Linkage of Free Radical Scavenging and Reproduction Inhibition
Natural antioxidants (such as vitamin E and rosmarinic acid) can scavenge free radicals produced by microbial metabolism, reducing their protective effects on their own DNA and proteins, while nisin prevents bacterial division by inhibiting cell wall synthesis. For example, in oily foods, when combined with vitamin E, vitamin E inhibits lipid oxidation and reduces microbial resistance caused by oxidative stress, making Nisin more likely to exert its antibacterial effect and extending the product shelf life.
2. Synergy in Disrupting Biofilms
Single preservatives have difficulty penetrating microbial biofilms (such as bacterial biofilms), while nisin can degrade extracellular polysaccharides in the biofilm matrix. Natural preservatives (such as lactoferrin and lysozyme) destroy the biofilm structure by decomposing peptidoglycan or interfering with the quorum sensing system. After combination, the two can synergistically disintegrate the biofilm barrier, allowing antibacterial components to act directly on the bacteria and avoiding microbial tolerance due to biofilm protection.
IV. Complementary Regulation of pH and Antibacterial Activity
Activity Enhancement of Nisin Under Acidic Conditions
Nisin exhibits stronger antibacterial activity in an acidic environment (pH below 4.5), and natural organic acids (such as malic acid and acetic acid) can reduce the system pH. On the one hand, this directly inhibits microorganisms other than acid-tolerant bacteria; on the other hand, it improves the membrane binding efficiency of Nisin. For example, in acidic fruit juices, when nisin is combined with malic acid, malic acid enhances Nisin's perforation ability by lowering the pH, while itself inhibiting yeasts and molds, forming a dual antibacterial system of "acidic environment-membrane damage".
V. Mechanism for Avoiding Microbial Drug Resistance
Multi-Target Action Reduces Drug Resistance Risk
Single preservatives easily induce microbial drug resistance through gene mutations (such as altering the structure of lipid II). The combination of Nisin and natural preservatives acts on multiple targets such as cell walls, cell membranes, and metabolic enzymes, making it difficult for microorganisms to produce multiple drug-resistant mutations simultaneously. For example, when combined with lysozyme, Nisin inhibits cell wall synthesis, and lysozyme decomposes formed peptidoglycan, causing bacteria to die due to inability to repair cell wall damage and significantly reducing the probability of drug-resistant strain generation.
The synergistic effect of nisin combined with natural preservatives is not a simple superposition of activities but a systematic disruption of microbial physiological functions through multi-dimensional mechanism collaboration. This circumvents the limitations of single components, demonstrating more efficient application potential in food preservation, medicine, and other fields.