ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Antibiotic Resistance and New Antimicrobial drugs
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1664896
This article is part of the Research TopicTargeting Major Human Fungal Pathogens: Novel Insights into Virulence and Antifungal TherapiesView all 6 articles
Cryptococcus neoformans by Agrochemical Azole Uniconazole through Upregulation of Efflux and Chromosomal Disomies
Provisionally accepted
- 1Department of Pharmacy, Jianyang People's Hospital, Chengdu, China
- 2Laboratory Department of Zhoucun District Center for Disease Control and Prevention, Zibo, China
- 3Department of Pharmacy, Zibo Zhoucun People’s Hospital, Zibo, China
- 4Shanghai Tenth People's Hospital, Shanghai, China
- 5Jinan Military General Hospital, Jinan, China
- 6960th Hospital of PLA, Tai'an, China
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Cryptococcus neoformans is a fungus naturally found in the environment, particularly in soil, bird droppings, and trees. Cryptococcosis, caused by Cryptococcus spp., primarily C. neoformans and C. gattii, 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 C. neoformans 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 AFR1 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.
Keywords: Cryptococcus neoformans, agrochemical azoles, medical azoles, cross-resistance, Aneuploidy, efflux, Afr1
Received: 13 Jul 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Zhang, Ma, Wang, Yang, Zhong and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yi Xu, Jinan Military General Hospital, Jinan, China
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