镰刀菌属广泛分布于土壤和植物中。它们可引起人类浅部和深部感染，作为新现、全球流行的真菌感染，发病率逐年增高，且死亡率极高，已严重地威胁人类的健康和生命。它们亦为重要的植物病原菌，可造成巨大的经济损失。目前，镰刀菌对几乎所有的临床抗真菌药物呈现显著的多重耐药性，使得抗真菌治疗变得异常艰难。且其对农用杀真菌剂的耐药状况亦日趋严重。本项目拟以茄病镰刀菌和尖孢镰刀菌的多重耐药株为研究对象，利用反向遗传学技术建立T-DNA插入突变体库，筛选药物敏感性异常突变体，寻找与耐药相关的未知基因、已知基因新功能或非编码序列，验证并注释其功能。结合生命组学数据，解析耐药相关基因的作用方式及调控网络，寻找对不同药物靶点起整体调控作用的关键基因；分析其系统进化关系；探讨固有耐药与获得性耐药的关系；寻找新的、潜在的抗真菌药物及阻断剂作用靶点。本研究亦可为其他真菌的耐药相关研究提供非常有价值的参考资料。

Fusarium is a large genus of fungus widely distributed in soil and in association with plants. They can cause superficial and systemic infections of human. As a new, global epidemic fungal infection, the incidence of fusaridiosis increased over these years, and the mortality rate was extremely high, which had seriously threatened the health and life of human. They are also important plant pathogens caused significant economic impacts. At present, Fusarium has a significant multidrug resistance to almost all clinical antifungal drugs, making treatment extremely difficult. And its resistance to agricultural fungicide is also serious. In this study, T-DNA insertion mutant library will be established by reverse genetics technology. Drug susceptibility changed mutants will be selected to find out the unknown genes, known genes with new function, or non-coding sequences associated with drug resistance. And the function of related genes will be verified and annotated. Based on omics technologies, the regulatory pathways related to drug resistance will be identified, which will help us to discover the critical genes regulated different drug targets, analyze the phylogenesis of these genes, understand the relationship between intrinsic and acquired resistance, and determine potential new targets for antifungal drugs and blockers. The findings may also provide a valuable reference for the study of drug resistance in other fungi.