Outlooks of endolysins with innolysins therapeutic potentials against antimicrobial resistance

Abstract The rise of antimicrobial resistance (AMR) caused by both Gram-positive (G +) and Gram-negative (G−) bacterial infections poses a significant threat to global health. The issue leads to finding alternative approaches to cope with the crisis. Endolysins, bacteriophage-encoded enzymes that lyse bacterial cell walls, offer a promising avenue to traditional antimicrobials. These enzymes target specific peptidoglycan (PG) bonds essential for bacterial integrity, leading to bacterial lysis. Unlike traditional antimicrobials, endolysins exhibit high specificity, potentially minimizing disruption to the host microbiome and reducing the selection pressure for resistance development. In addition, the inherent resistance to endolysins is rare, presenting a significant benefit for their application as a promising therapeutic agent. Therefore, this review focuses on exploring novel endolysins with innolysins from diverse bacteriophage sources and their therapeutic potential against both G + and G− bacterial infections. Additionally, it emphasizes their mechanisms of action and evaluates their potential as therapeutic agents. Furthermore, it adds an insightful contribution to the development of novel endolysins with innolysins designing strategies using artificial intelligence (AI) to combat antimicrobial-resistant infections.