NET-Inducing Ability of Cutibacterium acnes Clinical Isolates Is Associated With Pathogenicity in Acne Vulgaris

BACKGROUND: Cutibacterium acnes strains vary in virulence and inflammatory potential in acne vulgaris, but the role of the bacterial ability to induce neutrophil extracellular traps (NETs) in acne is unclear. METHODS: We collected 18 clinical isolates from acne patients and healthy controls and analyzed the correlation between C. acnes NET-inducing ability and bacterial virulence involved in acne vulgaris pathogenicity. RESULTS: Eighteen clinical strains were classified into 17 IA1 and 1 IA2 phylotypes. Supernatants from five acne-associated strains exhibited marked NET-inducing activity, which was strongly correlated with cytokine production and reactive oxygen species generation. The NET-inducing capacity of supernatants was also positively correlated with bacterial hemolytic activity against human erythrocytes and biofilm formation. In a mouse ear model, NET-inducing strains caused more-severe lesions than NET-noninducing strains. Whole-genome sequencing revealed substantial genetic variation between the NET-inducing strain (C009) and NET-noninducing ATCC strain. CONCLUSION: These findings suggest that NET induction represents one of virulence-associated phenotypes linked to pathogenicity in C. acnes-induced acne vulgaris.