Recent European origin of azole resistance in the critical priority fungal pathogen Aspergillus fumigatus

Recent European origin of azole resistance in the critical priority fungal pathogen Aspergillus fumigatus | 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 Biological Sciences - Article Recent European origin of azole resistance in the critical priority fungal pathogen Aspergillus fumigatus Matthew Fisher, Johanna Rhodes, Harry Chown, Rodrigo Leitao, Sam Hemmings, and 26 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7905776/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 Resistance to azole antifungals in Aspergillus fumigatus, a WHO Critical Priority fungal pathogen, is rising worldwide and threatens the efficacy of frontline therapies for invasive aspergillosis. This resistance has emerged largely through environmental selection driven by the extensive use of azole fungicides in agriculture and horticulture, yet its evolutionary origins remain obscure. Here, we analysed whole-genome sequences from 1,220 isolates collected over a century from 34 countries, revealing five distinct but interfertile genetic clusters spanning the global population. Azole resistance alleles were highly concentrated within particular clusters and were associated with mutator genotypes carrying defects in DNA repair, known to accelerate the accumulation of adaptive mutations. Two clusters exhibited resistance to multiple fungicide classes, including azoles, benzimidazoles, strobilurins and succinate dehydrogenase inhibitors, indicating the emergence of stacked multidrug resistance with no measurable fitness cost in vitro or in murine models. Molecular dating situates the expansion of resistant lineages in the latter half of the twentieth century, coinciding with the introduction and intensification of modern fungicide use. Phylogeographic reconstruction points to Western Europe—particularly intensive horticultural systems and the international bulb trade—as a major source of globally disseminated azole-resistant A. fumigatus, underscoring the urgent need for coordinated One Health surveillance and intervention. Health sciences/Diseases/Infectious diseases/Fungal infection Biological sciences/Evolution/Evolutionary genetics Earth and environmental sciences/Environmental sciences/Environmental impact Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMaterials.docx Supplementary Materials & Methods SupplementaryData2.xlsx SupplementaryData2 SuppFig3.pdf SuppFig3 SupplementaryData1.xlsx SupplementaryData1 SupplementaryData3.xlsx SupplementaryData3 SuppFig4.pdf SuppFig4 SuppFig6.pdf SuppFig6 SuppFig5.mp4 SuppFig5.mp4 SuppFig2.pdf SuppFig2 SuppFig1.pdf SuppFig1 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7905776","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":543575586,"identity":"38447e8b-b4ed-4d78-9334-ecaa1c6b1958","order_by":0,"name":"Matthew 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