Innovative Utilization of Endolysins for Future Battle Against Superbugs

Endolysins are fast-acting proteins produced by phages against bacteria, capable of breaking down the peptidoglycan layer of bacterial cells. In the current post-antibiotic era, endolysin-based therapeutics have received widespread attention. While native endolysins offer advantages such as rapid bacteriolytic activity, their clinical translation has been hindered by inherent limitations, including narrow spectrum, susceptibility to proteolytic degradation, and potential immunogenicity. Recent paradigm shifts in protein engineering and biotechnology are decisively overcoming these hurdles. This perspective highlights the transformative strategies revolutionizing the field, such as the creation of chimeric endolysins fused with outer membrane-permeabilizing peptides and the rational modulation of protein surface charge. Beyond that, endolysins demonstrate remarkable synergy with conventional antimicrobial agents such as colistin and berberine, enabling dose reductions and resensitizing resistant strains. Their application scope is broadening into areas such as food safety, where they effectively combat biofilms and multidrug-resistant pathogens across various food matrices. Moreover, critical challenges of stability and delivery are being addressed through advanced formulations. Endolysins are poised to evolve from a promising candidate into an innovative medical strategy against superbugs.