热带假丝酵母菌已成为侵袭性真菌感染的重要病原体，强毒力株更易引起免疫缺陷患者严重的全身感染。本课题组前期研究发现，氧化应激相关基因SOD2的表达上调与热带假丝酵母菌的毒力增强密切相关，但调控SOD2表达的转录因子及其增强菌株毒力的作用机制尚未明了。毒力增强的假丝酵母菌常伴有细胞形态的转变，我们前期发现与假丝酵母菌形态改变相关的调控基因UME6在临床分离的毒力强株中表达升高，而ume6Δ/ume6Δ菌株中SOD2基因的表达相应降低。本课题将构建SOD2和UME6基因缺失株、回复株和过表达株，观察菌株的活性氧、SOD水平及毒力强弱间的关系，明确UME6和SOD2表达对菌株毒力的影响；通过荧光素酶等实验验证UME6对SOD2的调控作用；并进一步观察UME6对SOD2基因表达调控与热带假丝酵母菌抵抗内源性ROS、增强其毒力间的关联性，最终解析热带假丝酵母菌毒力增强的可能机制。

Candida tropicalis has been one of the most important pathogens in invasive fungal infection, and those with strong virulence will cause serious system infection. A close relationship between overexpression of oxidative stress-related gene SOD2 and increased virulence was observed in our previous study, but transcription regulator of SOD2 and its role in the enhancement of virulence were still not clear. Morphological changes were observed in C. tropicalis isolates with strong virulence, and in our previous experiment, overexpression of morphological transcription factor UME6 was detected. The expression level of SOD2 decreased correspondingly in ume6Δ/ume6Δ C. tropicalis. In this project, effects of SOD2 and UME6 genes on virulence of C. tropicalis will be investigated by constructing the gene knock-out, reversed and overexpressed isolates, and analyzing their levels of ROS and SOD expression. Transcriptional regulation of UME6 on SOD2 gene will be detected by pGL3-basic luciferase reporter vector. Finally, the role of the transcriptional regulation in counteracting ROS and enhancing virulence of C. tropicalis will be explored. This project will provide new aspect of investigation on the mechanism of enhanced virulence of C. tropicalis.