Researchers may have uncovered factors contributing to the functional divergence of human commensal Cutibacterium acnes bacteria, according to a recent study published by Hajam et al in Nature Communications. The researchers explained that different phylotypes of C acnes bacteria may be associated with acne or healthy skin. They indicated that both phylotypes may have evolved from a common enzyme that acquired distinct enzymatic activity. In a murine model, the researchers analyzed how the evolution of two strains of the enzyme hyaluronidase—hyaluronidase A and B—may influence the development of acne-prone or healthy skin. They found that hyaluronidase A was proinflammatory, generated large-sized hyaluronic acid disaccharides, and drove toll-like receptor 2–dependent pathology; whereas hyaluronidase B was capable of degrading hyaluronic acid exclusively to hyaluronic acid disaccharides, which led to anti-inflammatory effects. The researchers noted that replacing an amino acid, Serine to Glycine near the catalytic site may enhance the enzymatic activity of hyaluronidase A and produce hyaluronic acid degradation intermediate to hyaluronidase A and B. Further, targeting hyaluronidase A with a peptide vaccine or inhibitor may be an effective treatment strategy for improving acne. In a companion press release on the findings from the University of California, San Diego, the study authors concluded: “Our anti-acne directed approach has the potential to revolutionize acne therapies by offering more targeted therapies. [W]e can now have more directed and effective anti-acne therapies while preserving the healthy skin microbiome.”