A major growing concern in the human and animal health sector is the emergence of antibiotic-resistant pathogenic bacteria due to the indiscriminate use of antibiotics. The exogenous application of bacteriophage endolysins causes abrupt lysis of the bacterial cell wall, which computes them as alternatives to antibiotics. Although naturally occurring endolysins may display limitations in solubility, lytic activity, and narrow lytic spectrum, novel strategies like developing chimeric endolysins and using endolysins in synergism with other antimicrobial agents are required to improve the lytic activity of natural endolysins. The modular structure of endolysins led to the development of novel chimeric endolysins via shuffling enzymatic and cell wall binding domains of different endolysins, using endolysins in a synergistic approach, and their applications in various in vitro and in vivo experiments and different applicable areas. This article aims to review the role of chimeric endolysins and their use in synergistic mode with other biofilm-reducing agents to control biofilm formation and deteriorating pre-formed biofilms in food, dairy, and medical industries. Promoting further development of phage technology and innovation in antibiotic therapy can achieve long-term sustainable development and economic returns.
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