源于农用三唑类化合物使用的农田土壤中烟曲霉抗药性相关cyp51A基因突变

项目名称： 源于农用三唑类化合物使用的农田土壤中烟曲霉抗药性相关cyp51A基因突变

项目编号： No.21477112

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 虞云龙

作者单位： 浙江大学

项目金额： 88万元

中文摘要： 烟曲霉引起的侵袭性曲霉病是免疫抑制人群主要致死因子，其治疗主要依赖于三唑类药物。然而，烟曲霉普遍对三唑类药物存在耐药性和抗药性，成为侵袭性曲霉病治疗的巨大挑战。揭示烟曲霉抗药性的来源有助于科学预防抗性形成并保障侵袭性曲霉病的控制。三唑类药物靶标酶基因cyp51A突变是烟曲霉抗药性主要成因。本项目针对三唑类药物结构类似的农用三唑类化合物使用诱导农田土壤中烟曲霉cyp51A突变并产生抗药性问题，研究：1）农田土壤中烟曲霉抗药性相关cyp51A突变及其普遍性；2）三唑类农药诱导烟曲霉产生的抗药性相关cyp51A突变；3）分析抗性烟曲霉在土壤中的适合度，明确抗性烟曲霉在土壤中生存、繁殖的持续性。项目研究将回答农用三唑类化合物使用导致农田土壤中烟曲霉产生突变并形成抗药性这一科学问题，从而从农药使用角度提出预防烟曲霉抗药性的途径，为烟曲霉抗药性的认识和预防提供新思路。

中文关键词： 农药；生态毒理；基因突变；抗药性；病原菌

英文摘要： Invasive aspergillosis caused by infection of Aspergillus fumigatus is a main lethal factor for the immunocompromised patients. Triazoles are the mainstay of therapy in infections with Aspergillus fumigatus. However, azole resistance is emerging in Aspergillus fumigatus isolates and becomes a new challenge in the management of invasive aspergillosis. The main resistance mechanism is a point mutation of cyp51A, the gene encoding the target enzyme of triazole antifungal drugs. To find the relationship between the emergency of resistant A. fumigates with mutation of cyp51A and the applications of triazoles in agriculture, the possible mutations of cyp51A in isolates of A. fumigates from agricultural fields and in soil samples successively received triazoles will be investigated in this study. The fitness of resistant A. fumigates in soil will also be studied to explore its persistence in soil. The results of this study will be helpful for the understanding the sources of the resistance in A. fumigates and finding the ways for the management of the resistance.

英文关键词： Pesticide;Ecotoxicology;Genetic mutation;Resistance;Pathogen