The antibacterial effect of Nisin on Gram-positive bacteria

Nisin, a natural antimicrobial peptide produced by lactic acid bacteria, exhibits significant inhibitory effects against various Gram-positive bacteria. Its bacteriostatic mechanism involves targeted destruction of bacterial cell membranes and interference with physiological functions, which can be elaborated as follows:

I. Antibacterial Spectrum Against Gram-Positive Bacteria

Nisin’s antibacterial activity is mainly directed at Gram-positive bacteria, including:

Pathogenic bacteria: Such as Staphylococcus aureus, Listeria monocytogenes, and Bacillus subtilis, which are sensitive to nisin due to their cell membrane structural characteristics;

Food spoilage bacteria: Such as Clostridium botulinum and Bacillus cereus. In food preservation, Nisin can extend shelf life by inhibiting these bacteria;

Some actinomycetes: It also has a certain inhibitory effect on some actinomycetes that cause plant diseases.

Notably, Gram-negative bacteria are generally insensitive to Nisin because their cell walls are surrounded by a lipopolysaccharide layer (outer membrane) that blocks Nisin penetration. However, destroying the outer membrane with reagents like EDTA can enhance nisin’s inhibitory effect on Gram-negative bacteria.

II. Antibacterial Mechanism: Multi-Step Destruction Targeting Cell Membranes

The core of nisin’s antibacterial effect lies in specific binding to the cell membranes of Gram-positive bacteria, triggering a series of structural and functional damages, including:

Recognition and binding to targets

Lipid II on the cell membrane of Gram-positive bacteria (a key pyrophosphate lipid carrier involved in cell wall peptidoglycan synthesis) is the critical target of nisin. The lysine residues in the nisin molecule can bind to the pyrophosphate groups of lipid II through electrostatic interactions. This specific recognition allows it to precisely target bacterial cell membranes, avoiding effects on host cells (e.g., human cells).

Cell membrane perforation and ion disorder

After binding to lipid II, the hydrophobic regions of nisin molecules insert into the phospholipid bilayer of the cell membrane. Multiple Nisin molecules aggregate with lipid II to form transmembrane channels (with a pore size of approximately 0.5–1 nm). These channels disrupt the integrity of the cell membrane, causing the outflow of important intracellular ions such as potassium ions and protons, while allowing a large influx of external water, leading to cell swelling and rupture (similar to "osmotic shock"). Studies have shown that within 10 minutes of nisin treatment, the intracellular potassium ion loss rate of bacteria can reach over 70%, rapidly inhibiting cellular metabolism.

Blocking cell wall synthesis

Lipid II is not only a component of the cell membrane but also a key precursor for cell wall peptidoglycan synthesis. The binding of nisin to lipid II competitively inhibits its participation in peptidoglycan assembly, resulting in the inhibition of bacterial cell wall synthesis. Since the cell wall of Gram-positive bacteria is mainly composed of peptidoglycan (accounting for 50%–90% of the dry weight of the cell wall), impaired cell wall synthesis prevents them from maintaining cell morphology, ultimately leading to lysis due to insufficient mechanical strength.

Inducing oxidative stress and DNA damage

Some studies have found that nisin can also stimulate bacteria to produce excessive reactive oxygen species (ROS), triggering membrane lipid peroxidation and DNA oxidative damage. For example, studies on Staphylococcus aureus have shown that intracellular ROS levels increase by 3–5 times after Nisin treatment, leading to DNA strand breaks and further accelerating bacterial death.

III. Key Factors Affecting Antibacterial Efficacy

The antibacterial activity of nisin is regulated by multiple factors, which should be noted in practical applications:

pH value: It is more stable and has stronger antibacterial activity under acidic conditions (pH 2–6); it is easily degraded in alkaline environments, with significantly reduced activity.

Temperature: It has good thermal stability (retaining more than 80% activity after sterilization at 121°C), making it suitable for preserving high-temperature processed foods.

Bacterial state: Bacteria in the logarithmic growth phase are more sensitive to nisin, while spores, due to their metabolically dormant state, require a higher concentration of Nisin for inhibition (usually combined with heat treatment to break spore dormancy).

Nisin efficiently inhibits Gram-positive bacteria through a multi-step mechanism of "target recognition – membrane perforation – blocking cell wall synthesis – inducing oxidative damage". Its characteristics such as natural origin, no toxic residues, and thermal stability make it widely applicable in food preservation, medical antibacterial (e.g., treatment of local infections), and other fields. Future research can further optimize its molecular structure to enhance the inhibitory effect on drug-resistant Gram-positive bacteria and expand application scenarios.