Comparative genomic analysis of clinically relevant human skin-associated fungi.

Fungal skin infections represent a significant global health burden, affecting approximately one billion people annually. Despite their prevalence and major global health impact, the molecular mechanisms underlying pathogenicity remain largely uncharacterized. Here we present the genomes of 66 fungal strains, representing highly prevalent and clinically relevant species associated with human skin infections. Using comparative genomics, we investigate whether the taxonomic groups in this collection of skin fungi differ in their genome architecture, metabolic capacity, secreted enzyme repertoires, adhesin content, and predicted virulence determinants. These analyses reveal substantial variation in genome size and gene contents, indicating genome compaction occurred as the fungi transitioned from free-living to host-associated lifestyles. We report two non-hybrid strains of Trichosporon ovoides, the causative agent of white piedra. Our analyses reveal substantial differences in metabolic adaptations across skin-associated fungi, corresponding to body-site and nutrient niches. Significant differences are also observed in the distribution of virulence factors and adhesins, which are imperative for biofilm formation and antifungal resistance. We discuss metabolic adaptation and virulence mechanisms revealed by our data in the context of clinical presentations, highlighting shared and lineage-specific signatures of adaptations. Together, these insights advance our understanding of skin-associated fungi and their mechanisms of infection.