Bacteriophage lysins: a promising strategy for combating foodborne pathogens in food safety

causing millions of infections and significant economic losses annually. Phage and endolysin therapies have emerged as promising environmentally friendly strategies for pathogen control. Bacteriophage lytic enzymes, which are proteins produced during the late stage of phage infection, offer advantages over whole phages, including rapid bactericidal action, a broad antibacterial spectrum, and a low risk of inducing resistance. This review summarizes the structure, classification, and lytic mechanism of phage lysins, as well as their application in combating foodborne pathogens across various food matrices, including meat, dairy products, agricultural produce, and seafood. Furthermore, these lysins have demonstrated promising potential in biofilm removal. Meanwhile, this review discusses multiple improvement strategies that have been developed to enhance the activity of lysins against both Gram-positive and Gram-negative bacteria. These include domain truncation, site-directed mutagenesis, and domain shuffling to overcome insufficient stability and suboptimal activity in food environments, as well as co-administration with outer membrane permeabilizers, encapsulation and engineered lysins (e.g., Artilysins, Innolysins, and Lysocins) to breach the outer membrane barrier of Gram-negative bacteria. Furthermore, the introduction of computer-aided and bioinformatics tools has provided new avenues for the high-throughput screening and rational design of lysins. Although challenges such as low screening efficiency, unstable activity in food matrices, non-uniform efficacy endpoints, regulatory data requirements, high production costs, and limited consumer acceptance persist, lysins, as green and efficient natural antimicrobial proteins, still exhibit broad application prospects in food biocontrol.