{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:23:12Z","timestamp":1788452592283,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01 AI143197"],"award-info":[{"award-number":["R01 AI143197"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["P30CA021765"],"award-info":[{"award-number":["P30CA021765"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007737","name":"St. Jude Children's Research Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012524","name":"ALSAC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the frequency of cyp51A variants among a contemporary collection of triazole-resistant Aspergillus fumigatus clinical isolates from the USA and compare their specific contribution to reduced triazole susceptibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The genomes of 87 isolates with decreased susceptibility to at least one mould-active triazole antifungal collected between 2007 and 2020 were sequenced. The cyp51A variants were identified and genetically introduced into a cyp51A-null strain. Antifungal susceptibilities for the mould-active triazole antifungals were determined following CLSI guidelines, and variant positions were mapped after protein homology modelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Most clinical isolates (60%) carried one of 15 variants that reduced susceptibilities to short-chain (G448S, Y121F, TR46\/Y121F\/T289A and TR46\/Y121F\/T289A\/N512), long-chain (P216L, F219S and substitutions in the G54 and M220 residues) or multiple (TR34\/L98H and TR34\/L98H\/S297T\/F495I) triazoles. While TR34\/L98H and TR46\/Y121F\/T289A were among the most common variants affecting susceptibility, occurring in 13 and 9 isolates, respectively, variants exclusively affecting the coding region and influencing susceptibility were most common, occurring in 31 isolates. A total of 14 isolates (16%) exhibited reduced susceptibility that could not be explained by variants in any known resistance determinants (cyp51A, hmg1 or hapE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate the range of mutations affecting triazole resistance among US isolates and provide a much-needed side-by-side comparison of the impact of these variants on the most currently used mould-active triazole antifungals. Moreover, they underscore the extent to which triazole resistance remains unexplained by known genetic determinants and the need for further discovery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag124","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:45:55Z","timestamp":1774615555000},"source":"Crossref","is-referenced-by-count":1,"title":["Prevalence of\n                    <i>cyp51A<\/i>\n                    variants in a US collection of\n                    <i>Aspergillus fumigatus<\/i>\n                    clinical isolates and comparative analysis of their contribution to triazole antifungal resistance"],"prefix":"10.1093","volume":"81","author":[{"given":"Luisa Fernanda","family":"G\u00f3mez Londo\u00f1o","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, St Jude Children\u2019s Research Hospital , Memphis, TN 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Children\u2019s Research Hospital , Memphis, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6828-5618","authenticated-orcid":false,"given":"Vanessa","family":"Meza-Perez","sequence":"additional","affiliation":[{"name":"Department of Host-Microbe Interactions, St Jude Children\u2019s Research Hospital , Memphis, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2225-5122","authenticated-orcid":false,"given":"Nathan P","family":"Wiederhold","sequence":"additional","affiliation":[{"name":"Fungus Testing Laboratory, Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio , San Antonio, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anang A","family":"Shelat","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Therapeutics, St Jude 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