Zheng Qiushi, Zhang Qiuyu, Bing Jian, Ding Xuefen, Huang Guanghua
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
College of life sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Mol Microbiol. 2017 Dec;106(6):999-1017. doi: 10.1111/mmi.13862. Epub 2017 Nov 9.
Phenotypic switching is a strategy by which microbial organisms adapt to environmental changes. The human fungal pathogens, Candida albicans and Candida tropicalis, are closely related species and capable of undergoing morphological transitions. C. albicans primarily exists in human or warm-blooded animals as a commensal, whereas C. tropicalis not only exists as a commensal but also is widely distributed in the environment. In this study, we describe the environmental and genetic regulatory mechanisms of white-opaque switching in C. tropicalis, which is associated with virulence and sexual mating. A comparative study with C. albicans demonstrated that C. tropicalis responds to environmental stimuli, such as elevated CO levels and pH changes, in opposite manners. An acidic pH and elevated CO levels promote the opaque phenotype in C. albicans but have an opposite effect in C. tropicalis, whereas alkaline pH conditions facilitate white-to-opaque switching and sexual mating in C. tropicalis. The conserved Rim101-mediated pH sensing and Ras1-cAMP/PKA signaling pathways are involved in this regulation. By screening an overexpression library of transcription factors, we identified 26 white-opaque regulators, including WOR1, AHR1, EFG1, CUP9, BCR1 and SFL2. Transcriptional analysis indicated that the pH sensing and Ras1-cAMP/PKA signaling pathways and transcriptional regulators coordinately regulate white-to-opaque switching.
表型转换是微生物适应环境变化的一种策略。人类真菌病原体白色念珠菌和热带念珠菌是密切相关的物种，能够进行形态转变。白色念珠菌主要作为共生菌存在于人类或温血动物体内，而热带念珠菌不仅作为共生菌存在，还广泛分布于环境中。在本研究中，我们描述了热带念珠菌白色-不透明转换的环境和遗传调控机制，该转换与毒力和有性交配有关。与白色念珠菌的比较研究表明，热带念珠菌对环境刺激（如二氧化碳水平升高和pH变化）的反应方式相反。酸性pH和升高的二氧化碳水平促进白色念珠菌的不透明表型，但在热带念珠菌中具有相反的作用，而碱性pH条件促进热带念珠菌的白色-不透明转换和有性交配。保守的Rim101介导的pH感应和Ras1-cAMP/PKA信号通路参与了这一调控。通过筛选转录因子过表达文库，我们鉴定出26种白色-不透明调节因子，包括WOR1、AHR1、EFG1、CUP9、BCR1和SFL2。转录分析表明，pH感应和Ras1-cAMP/PKA信号通路以及转录调节因子协同调节白色-不透明转换。
