Zhang Maoji, Ma Weihua, Wang Jing, Yang Feng, Zhong Jingjing, Xu Yi
Department of Pharmacy, Jianyang People's Hospital, Chengdu, China.
Jinzhou Medical University Graduate Training Base (The 960th Hospital of PLA), Jinan, China.
Front Cell Infect Microbiol. 2025 Sep 8;15:1664896. doi: 10.3389/fcimb.2025.1664896. eCollection 2025.
is a fungus naturally found in the environment, particularly in soil, bird droppings, and trees. Cryptococcosis, caused by spp., primarily and , 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 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 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.
是一种自然存在于环境中的真菌，尤其是在土壤、鸟粪和树木中。由隐球菌属物种引起的隐球菌病主要影响肺部和中枢神经系统，对人类健康构成重大威胁。农用化学品在全球范围内广泛使用，大多数施用的农用化学品会扩散到环境中，这可能对人类健康产生直接和间接影响。本研究使用H99实验室菌株研究植物生长调节剂烯效唑（UCZ）对新型隐球菌抗真菌耐药性的影响。我们发现UCZ具有强大的抗真菌活性，暴露于UCZ会诱导基因组改变，导致对农用和医用唑类药物产生交叉耐药性。适应株在全基因组范围内表现出基因表达改变，包括外排基因，以及外排泵活性增加。删除和过表达特定基因证明了其在介导对唑类药物耐药性中的作用，对两性霉素B敏感性产生了意想不到的影响。这些发现强调了农用化学品对抗真菌耐药性发展的重大影响，以及在耐药性管理策略中考虑环境暴露的重要性。
