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 high quality genomic datasets for 51 fungal strains, representing highly prevalent and clinically relevant species associated with human skin infections. Comparative genomics 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 analysis reveals substantial differences in metabolic adaptations across skin-associated fungi, corresponding to distinct body-site and nutrient niches. Significant differences were also present 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 adaptations. Together, these insights advance our knowledge of skin-associated fungi and their infection mechanisms while providing valuable resources and a foundation for future analyses to improve diagnostics and therapeutics for diverse diseases.