Phage endolysins as alternative antimicrobials: mechanisms, clinical progress, and emerging resistance frameworks

Phage endolysins are increasingly recognized as alternatives to antibiotics for mitigating the growing threat of antimicrobial resistance. Since their initial identification in the 1950s, phage endolysins have been extensively demonstrated to effectively combat bacterial infections in animal models and human patients. Although phage endolysins have completed Phase II and III clinical trials, potential obstacles and challenges associated with their large-scale use remain largely undefined. This review examines the potential of phage endolysins and the challenges they face in addressing infections caused by antibiotic-resistant bacteria in the future. We conducted a comprehensive overview of the historical development, bactericidal mechanisms, clinical progress, and resistance of phage endolysins. The information presented herein may facilitate the design of novel, potent endolysins and provide strategic insights for addressing phage endolysin resistance.