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The composition of the skin microbiome varies widely among individuals sampled at the same body site. A key question is which molecular factors determine strain-level variability within sub-ecosystems of the skin. We used a genomics-guided approach to identify an antibacterial biosynthetic gene cluster in Cutibacterium acnes (formerly Propionibacterium acnes) that is widely distributed across individuals and skin sites. Experimental characterization of this cluster enabled the identification of a new thiopeptide antibiotic, cutimycin. Analysis of individual human skin hair follicles showed that cutimycin is an important factor regulating colonization resistance against Staphylococcus species.

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