Large-scale investigation for antimicrobial activity reveals newly-identified defensive species across the healthy skin microbiome
- Uyen Thy Nguyen
- Rauf Salamzade
- Shelby Sandstrom
- Mary Hannah Swaney
- Elizabeth C. Townsend
- Sherrie Y. Wu
- J. Z. Alex Cheong
- Joseph A. Sardina
- Isabelle Ludwikoski
- Mackinnley Rybolt
- Hanxiao Wan
- Caitlin M. Carlson
- Jordana Ferro
- Owen McArthur
- Won Se Suh
- Robert Zarnowski
- David R. Andes
- Cameron R. Currie
- Lindsay R. Kalan
2026-05-25
The skin microbiome forms a protective barrier to pathogens, including through the production of antimicrobial metabolites. Here, we present EPIC HHS , a large and taxonomically diverse skin microbiome culture collection of 968 strains from eight body sites. EPIC HHS captures >95% of cumulative species-level abundance across 268 skin metagenomes. It includes isolates present at <0.1% relative abundance and the cultured representatives for eight species not previously isolated, markedly expanding current skin microbiome resources. A contact-independent screen assaying ~14,000 pairwise interactions against 22 pathogens revealed widespread antagonism with striking enrichment for antifungal activity. Finally, functional genomic analysis, including 287 EPIC HHS isolate genomes, demonstrated a diverse landscape of skin-associated biosynthetic gene clusters that are mostly uncharacterized. Together EPIC HHS , its functional and genomic characterization, establishes the skin microbiome as a reservoir for specialized metabolism and provides a platform for microbiome-based antimicrobial discovery.