598 Identification of a human skin commensal bacterium that selectively kills cutibacterium acnes

Abstract

Cutibacterium acnes (C. acnes) is one of the most common bacterial species on human skin and can promote acne vulgaris. Most current therapeutics for acne are antibiotics that fail to discriminate C. acnes from the other skin resident microflora, many of which have important roles in health. Such approaches have significant drawbacks due to poor antimicrobial activity on the skin surface and emergence of antibiotic resistance. The microbiome represents a vast resource for drug discovery as its members engage in constant conflict to outcompete one another by deploying diverse strategies for survival. Our aim was to identify and develop new antimicrobials from the skin microbiome, as a biotherapy for acne. To do this, we conducted a functional screen of coagulase-negative staphylococci collected from swabs of the face and arms of healthy individuals and recorded their antimicrobial activity against C. acnes. Amongst the antimicrobial hits, we found that Staphylococcus capitis (S. capitis E12) strain exhibited potent and selective activity against all acne- and health-associated C. acnes strains tested, but not against several other important commensal bacteria. HPLC and LC/MS analyses of S. capitis E12 supernatant identified the antimicrobial metabolites as four distinct amphipathic phenol soluble modulin β (PSMβ) peptides. These PSMβ peptides were found to act synergistically and were not toxic to human keratinocytes. Formulation and application of a purified S. capitis E12 extract onto ex vivo pig skin colonized with C. acnes, resulted in a 1-log decrease (p> 0.02) in CFU after 24 h. More impressively, the extract applied topically onto SKH1 mouse skin colonized with C. acnes, resulted in a 3-log decrease (p>0.01) in CFU after 48 h. Overall, these data show how some peptides from the skin microbiome can be highly selective against C. acnes and highlights their potential application as a biotherapy for acne vulgaris.