Phage-Derived Endolysins Targeting Cutibacterium acnes: A Scoping Review

Background: Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit in which Cutibacterium acnes plays an important role in disease pathogenesis. Rising antimicrobial resistance has intensified interest in selective antimicrobial strategies for acne vulgaris. Bacteriophage-derived endolysins may offer targeted antibacterial activity while potentially sparing the skin microbiota. This scoping review aimed to map current evidence regarding endolysins targeting C. acnes and to evaluate their antibacterial activity, selectivity, safety, formulation challenges, and translational potential. Methods: This scoping review was conducted in accordance with PRISMA-ScR guidelines. Searches on PubMed, Scopus, Embase, Web of Science, and Google Scholar were performed in February 2026. Experimental studies, academic theses, and patent documents investigating phage-derived endolysins active against C. acnes were included and narratively synthesised. Results: Five peer-reviewed studies, three academic theses, and seven patent documents were included. Most available evidence originated from in vitro studies, with only one short-term clinical investigation identified. Endolysins and engineered derivatives demonstrated rapid bactericidal activity against C. acnes, including multidrug-resistant isolates, while several constructs exhibited minimal activity against selected commensal skin bacteria. Lysin-derived peptides retained activity under physiologically relevant pH and temperature conditions and in the presence of retinoic acid. Major translational challenges included limited stability of enzyme formulations, insufficient pilosebaceous unit penetration data, lack of anti-biofilm evidence and unstandardised microbiome assessment methods. Conclusions: Phage-derived endolysins represent a promising targeted therapeutic strategy for acne vulgaris. However, current evidence remains predominantly preclinical, and substantial translational barriers related to delivery, stability, safety, anti-biofilm efficacy, microbiome homeostasis, and clinical validation must be addressed before routine dermatological application.