人类致病丝状真菌DNA条形码筛选及宿主适应性进化

Human mycoses caused by filamentous fungi are relatively severe diseases with limited treatment options and affect human health. The quantity and type of pathogenic filamentous fungi are increasing rapidly. The cases due to new species were found and reported constantly. On the basis of more than 4,000 strains isolated from patients and reserved in our collection, we plan to use multilocus sequence typing and multiple gene genealogical analysis to understand the characteristics of fungal species distribution and community structure; compare the multiple genes conservatism and variability within species to screen DNA barcode; study the phyletic evolution of anti-oxidative stress and drug resistance related genes. The aim of the study is to recognize and classify abundant pathogenic strains appropriate and analyze the evolution mechanism of anti-oxidative stress and drug resistance related genes under host stress. The study will provide new explanation of fungi pathogenesis to human and fungal drug resistance.

丝状真菌导致的各种人类真菌病，危害大，治疗难。人类致病性丝状真菌感染日益增多，感染种类呈多样化，新致病菌被不断发现。本项目拟在前期收集保藏的4000余株致病丝状真菌基础上，利用多基因序列分析与多基因谱系相合性分析方法，解析我国致病性丝状真菌的菌种分布和群体结构；通过比较多个基因或片段种内保守性和变异性，筛选出恰当的核心片段作为DNA条形码；对重要丝状真菌的氧化压力抵抗以及耐药相关的宿主适应性基因进行系统进化考察，准确识别和合理分类我国丰富的致病丝状真菌，并从系统发育层面，分析致病丝状真菌氧化压力抵抗和耐药性相关基因在宿主压力下的进化机制，为真菌人类致病和耐药发生提供新的解释。

人类致病性丝状真菌感染日益增多，感染种类呈多样化，新致病菌被不断发现。本研究采用多基因序列分析和多基因谱系相合性分析方法，完成了我国帚霉、赛多孢霉、枝顶孢霉、暗色真菌、皮肤癣菌的菌种分布和群体结构的研究，筛选出适合上述致病丝状真菌鉴定的DNA条形码，发现并命名两种新的帚霉。完成对少见致病丝状真菌的体外药敏谱的描绘。对两种重要致病丝状真菌：毛霉目真菌和皮肤癣菌进行了蛋白质谱种系发生分析，将菌种分类进化的研究角度从基因层面拓展到蛋白水平。研究成果已推广应用于临床致病丝状真菌确认和鉴定，新菌种的发现和报告中。