Nisin raw materials, research on drug resistance

Nisin is a natural antibacterial peptide produced by Lactococcus lactis and is widely used as a preservative in the food industry. However, with the long-term use of Nisin, some bacteria have gradually developed resistance. The following is a study on the resistance mechanism of bacteria to Nisin and the corresponding countermeasures:

I. Bacterial Resistance Mechanisms

Changes in the structure of the cell membrane: The bacterial cell membrane is the main target of Nisin. Some bacteria reduce the affinity of Nisin by changing the composition and structure of the cell membrane. For example, increasing the saturation or chain length of fatty acids in the cell membrane makes the cell membrane more compact, reducing the chance of Nisin inserting into the cell membrane, thus decreasing its antibacterial activity.

Thickening of the cell wall: Some bacteria increase the thickness of the cell wall or change the composition of the cell wall to form a physical barrier that prevents Nisin from approaching the target on the cell membrane. For instance, some Gram-positive bacteria increase the cross-linking degree of peptidoglycan in the cell wall, making the cell wall more rigid and difficult for Nisin to penetrate, thereby developing resistance.

Active efflux system: Certain bacteria can produce active efflux pumps that pump Nisin, which has entered the cell, out of the cell, reducing the concentration of Nisin inside the cell to a sub-inhibitory level and thus avoiding damage to the cell by Nisin. These efflux pumps are usually transmembrane proteins that can specifically or non-specifically recognize and transport Nisin.

Enzymatic modification: Some bacteria can produce specific enzymes to modify Nisin, causing it to lose its antibacterial activity. For example, certain proteases can hydrolyze the peptide bonds of Nisin and disrupt its molecular structure. Some enzymes can also modify the amino acid residues of Nisin, such as phosphorylation and acetylation, changing its charge or spatial structure and reducing its binding ability to the target.

II. Countermeasures

Rational use of Nisin: Avoid the abuse and excessive use of Nisin and formulate reasonable usage specifications and dosage standards. According to different food types and processing technologies, precisely control the addition amount of Nisin, which can effectively inhibit the growth of spoilage bacteria and pathogenic bacteria and reduce the selective pressure of bacteria exposed to Nisin, thereby reducing the risk of resistance development.

Combined use of antibacterial agents: Combine Nisin with other antibacterial agents that have different mechanisms of action to exert a synergistic antibacterial effect. For example, Nisin can be used in combination with organic acids, phenolic compounds, lysozyme, etc. These antibacterial agents act on different targets of bacteria, making it difficult for bacteria to develop resistance to multiple antibacterial agents simultaneously, thus improving the antibacterial effect, reducing the amount of Nisin used, and indirectly reducing the development of resistance.

Development of new antibacterial peptides: Based on the structure and mechanism of action of Nisin, use genetic engineering technology to modify and optimize it to develop new antibacterial peptides with higher antibacterial activity, a broader antibacterial spectrum, or less likelihood of inducing resistance. For example, perform site-directed mutagenesis on the amino acid sequence of Nisin, change the amino acid residues at key positions, enhance its affinity for the target on the cell membrane, or improve its stability against enzymatic modification.

Strengthen monitoring and management: Establish a complete monitoring system for bacterial resistance, regularly monitor the resistance of bacteria isolated from food to Nisin, and promptly grasp the prevalence trend and transmission rules of resistant bacteria. At the same time, strengthen the supervision of food production enterprises to ensure that they use Nisin in strict accordance with the regulations and severely deal with violations.