Enzybiotics

Enzybiotics are enzymes with antibacterial activity used as therapeutic agents to treat bacterial infections. They include bacteriophage-derived lytic enzymes, such as endolysins, and other muralytic enzymes engineered to target bacterial cell walls. The term encompasses natural enzymes and engineered variants designed to enhance stability, spectrum, or pharmacological properties.

Mechanism of action involves cleaving essential bonds in peptidoglycan, the structural component of bacterial cell walls. This enzymatic degradation weakens the cell wall and leads to rapid bacterial lysis. Enzybiotics often exhibit high specificity for particular bacteria or groups, which can reduce collateral damage to the native microbiota. Activity is typically greater against Gram-positive bacteria because their peptidoglycan is more exposed; access to Gram-negative species is more challenging due to the outer membrane, though engineering approaches and combination strategies have shown promise in overcoming this barrier.

Development and applications have grown in response to antimicrobial resistance. Enzybiotics are being explored for topical and systemic therapies against infections caused by resistant pathogens, as adjuncts to conventional antibiotics, and in non-clinical settings such as food safety and agriculture. Several candidates have entered clinical development, particularly lysins targeting Staphylococcus aureus and other priority pathogens, with varying stages of trials and regulatory considerations.

Advantages of enzybiotics include rapid bactericidal activity and high specificity, which can minimize disruption of beneficial microbiota. Limitations involve delivery to the infection site, potential immunogenicity, stability under physiological conditions, manufacturing costs, and regulatory hurdles. Ongoing research seeks to broaden spectra, improve pharmacokinetics, and integrate enzybiotics into combination therapies. See also lysins and phage therapy.