Comparative genomic analysis of clinically relevant human skin-associated fungi | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comparative genomic analysis of clinically relevant human skin-associated fungi Beatrice Dyring-Andersen, Sofie Agerbæk, Knud Nielsen, Julie Sølberg, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6700810/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract 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. Health sciences/Pathogenesis/Infection Biological sciences/Microbiology/Fungi/Fungal pathogenesis Biological sciences/Microbiology/Clinical microbiology Biological sciences/Biotechnology/Genomics/Phylogenomics fungal genomics superficial fungal infections tinea candida dermatophyte onychomycosis Full Text Additional Declarations Table 1 to 3 are available in the Supplementary Files section. Supplementary Files suptable4.pdf Supplementary table 4 suptable1.pdf Supplementary table 1 table1.pdf Table 1 suptable3.pdf Supplementary table 3 suptable2.pdf Supplementary table 2 table2.pdf Table 2 table3.pdf Table 3 suptable5.pdf Supplementary table 5 TablesComparativeanalysisofskinfungiNCOMMS2535116.xlsx Tables_Comparative-analysis-of-skin-fungi Table1accessionstodateNCOMMS2535116.pdf Accessions_to_date Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6700810","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":468699203,"identity":"ca5b3b6c-9fc9-4da1-827e-4a1b3af5c459","order_by":0,"name":"Beatrice 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