{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:47:59Z","timestamp":1790214479624,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Cryptococcus neoformans<\/jats:italic> is a fungus naturally found in the environment, particularly in soil, bird droppings, and trees. Cryptococcosis, caused by <jats:italic>Cryptococcus<\/jats:italic> spp., primarily <jats:italic>C. neoformans<\/jats:italic> and <jats:italic>C. gattii<\/jats:italic>, poses a significant threat to human health. Agrochemicals are widely used worldwide, and most applied agrochemicals are dispersed into the environment, which can have direct and indirect effects on human health. This study investigates the impact of the plant growth regulator uniconazole (UCZ) on antifungal resistance in <jats:italic>C. neoformans<\/jats:italic> using the H99 laboratory strain. We found UCZ to have potent antifungal activity, and exposure to UCZ induced genomic alterations, resulting in cross-resistance to both agricultural and medical azoles. The adaptors showed altered gene expressions across the genome, including efflux genes, as well as increased efflux pump activity. Deletion and overexpression of <jats:italic>AFR1<\/jats:italic> demonstrated its role in mediating resistance to azoles, with unexpected effects on amphotericin B sensitivity. These findings underscore the significant impact of agricultural agrochemicals on antifungal resistance development and the importance of considering environmental exposures in resistance management strategies.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1664896","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T06:16:33Z","timestamp":1757312193000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Induction of pan-azole resistance in Cryptococcus neoformans by agrochemical azole uniconazole through upregulation of efflux and chromosomal disomies"],"prefix":"10.3389","volume":"15","author":[{"given":"Maoji","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-014-0100-8","article-title":"YMAP: a pipeline for visualization of copy number variation and loss of heterozygosity in eukaryotic pathogens","volume":"6","author":"Abbey","year":"2014","journal-title":"Genome Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1093\/jac\/dku554","article-title":"Identification and properties of plasma membrane azole efflux pumps from the pathogenic fungi Cryptococcus gattii and Cryptococcus neoformans","volume":"70","author":"Basso","year":"2015","journal-title":"J. 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