Antibiotic resistance has become one of the most critical global health threats. As conventional antibiotics lose efficacy against multidrug-resistant (MDR) pathogens, enzyme-based antibiotics (enzybiotics) are emerging as an innovative therapeutic option. These molecules act directly on the bacterial cell wall or membrane, enabling rapid bactericidal activity and reducing the likelihood of resistance development.

A key example is lysozyme, a natural innate immune enzyme active mainly against Gram-positive bacteria; its stability and spectrum have been enhanced through PEGylation, nanocarrier systems, and protein engineering. Phage-derived enzymes (endolysins, holins) show strong activity against resistant pathogens such as MRSA and VRE and can disrupt biofilms, offering promise for chronic infections.

Challenges such as high production cost, short half-life, immunogenicity, and limited tissue penetration remain. However, advances in recombinant DNA technology, nanoparticle-based delivery systems, and AI-driven protein engineering are addressing these barriers.

Looking ahead, personalized medicine will enable tailored enzyme-based therapies adapted to each patient’s pathogen genome and immune profile, providing a novel and strategic tool against antibiotic-resistant infections beyond the limits of conventional antibiotics.