Acne is the most common dermatological condition that affects close to 80% of the 10-30 years old cohort with varying degrees of severity, and can cause significant psychosocial issues that can be debilitating for the patients. There is a large unmet medical need in acne treatments because of the increasing prevalence of antibiotic-resistant bacteria and the significant side effects of current treatments. Enzybiotics is a class of antimicrobial enzymes derived from bacteriophages that break down bacterial cell wall during the lytic cycle, are capable of killing the cell even when applied outside and are less prone to inducing resistance. We discovered a novel class of bacteriophage-derived enzymes that unexpectedly can selectively kill the bacteria that cause acne. We aim to develop the most potent and selective antimicrobial enzymes to target the bacteria involved in acne but not normal microbiota. Success in this proof-of-concept proposal will lead to further development of these antimicrobial proteins as effective acne therapeutics superior to current treatments.