From Streptococcus lactis to Nisin

The discovery of nisin from Streptococcus lactis stands as a pivotal milestone in humanity’s exploration of natural antimicrobial substances. This journey not only weaves together interdisciplinary breakthroughs in microbiology, food science, and medicine but also reveals the immense potential of natural antimicrobial peptides in combating drug-resistant bacteria.

I. Streptococcus lactis: The "Invisible Guardian" in Fermented Foods

The story begins with humanity’s millennia-old practice of fermenting foods. As early as ancient times, people observed that dairy products fermented by lactic acid bacteria—such as yogurt and cheese—were more preservable and less prone to spoilage than unfermented foods. In the late 19th century, the rise of microbiology provided a scientific explanation for this phenomenon: during fermentation, lactic acid bacteria (including Streptococcus lactis, now classified under Lactococcus lactis) produce a "bacteriostatic substance" that inhibits the growth of spoilage and pathogenic bacteria.

In 1928, British microbiologist R. G. Thornley first observed this phenomenon in cultures of Streptococcus lactis: when Streptococcus lactis was co-cultured with other Gram-positive bacteria (e.g., Staphylococcus aureus), the growth of the latter was significantly inhibited, forming a distinct zone of inhibition. This discovery challenged the prevailing belief that "only fungi produce antibiotics," suggesting that certain bacteria themselves secrete antimicrobial substances. However, limited by technical conditions, the chemical nature of this substance remained a mystery for decades, vaguely referred to as "the antibacterial factor of Streptococcus lactis."

II. Isolation and Identification of Nisin: From "Bacteriostatic Phenomenon" to "Substance Essence"

In the 1930s, British scientists discovered that the bacteriostatic effect of Streptococcus lactis was highly specific—it was effective only against Gram-positive bacteria, with no significant impact on Gram-negative bacteria or fungi. This property, distinct from known antibiotics like penicillin, sparked academic curiosity about its chemical structure.

In 1944, researchers first isolated this active substance from Streptococcus lactis fermentation broth and named it "Nisin" (derived from the abbreviation of "Lactococcus lactis inhibitor"). Early studies revealed that Nisin was extremely stable: it could withstand high-temperature treatments (e.g., pasteurization) in acidic environments and was not easily decomposed by human digestive enzymes, giving it unique advantages in food preservation. However, due to limitations in isolation and purification techniques, it was not until 1969 that scientists identified its nature through amino acid sequencing—a 34-amino-acid peptide containing rare modified amino acids such as lanthionine, which are critical to its antimicrobial activity. This unique chemical structure classified it as a "lantibiotic," making it the first member of the natural antimicrobial peptide family with a defined structure.

III. From Laboratory to Industrialization: The Application Revolution of Nisin

The discovery of Nisin quickly transcended basic research. In 1960, the United Kingdom officially approved Nisin as a food preservative, making it the first commercially available natural antimicrobial peptide. Its advantages include:

Safety: As a metabolite of Streptococcus lactis, Nisin is non-toxic and non-side-effect to humans, and can be decomposed by intestinal flora without accumulating in the body. This allowed it to rapidly replace some chemical preservatives (e.g., nitrites) in the food industry.

Efficiency: Even at extremely low concentrations (microgram levels), it inhibits various Gram-positive pathogens (e.g., Staphylococcus aureus, Listeria), particularly effective against spoilage-causing bacteria like Clostridium and Bacillus. It is widely used in preserving dairy products, meat, and canned foods.

Since the 1980s, with the growing problem of drug-resistant bacteria, the medical value of Nisin has been re-recognized. Studies found that its antimicrobial mechanism is unique: it disrupts bacterial cell membrane integrity by forming transmembrane channels, leading to intracellular substance leakage and cell death, making it less likely to induce bacterial resistance. This property positions it as a potential candidate against multidrug-resistant Gram-positive bacteria (e.g., methicillin-resistant Staphylococcus aureus, MRSA), with multiple clinical trials exploring its applications in skin infections and oral inflammation.

IV. Insights and Future: New Dimensions in Exploring Natural Antimicrobial Peptides

The journey from Streptococcus lactis to Nisin provides a paradigm for researching natural antimicrobial peptides:

Mining microbial resources: As a "beneficial bacterium" in fermented foods, Streptococcus lactis and its antimicrobial metabolites suggest that environmental microorganisms (especially symbiotic flora) harbor a wealth of undiscovered antimicrobial substances.

Structure-function relationships: The strong correlation between Nisin’s lanthionine modifications and its antimicrobial activity has driven research on artificially engineered antimicrobial peptides. Genetic engineering optimizations of its structure can enhance stability or expand its antimicrobial spectrum (e.g., activity against Gram-negative bacteria).

Today, Nisin has become a "benchmark" in natural antimicrobial peptide research, and the process of discovering it from Streptococcus lactis confirms a truth: humanity’s exploration of the microbial world often begins with questioning daily phenomena and culminates in a profound understanding of life’s laws—this is the most compelling trajectory of scientific discovery.