Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Institute of Infectious Disease and Biosecurity and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
Nat Commun. 2023 Apr 12;14(1):2067. doi: 10.1038/s41467-023-37755-8.
The human fungal pathogen Candida albicans can switch stochastically and heritably between a "white" phase and an "opaque" phase. Opaque cells are the mating-competent form of the species, whereas white cells are thought to be essentially "sterile". Here, we report that glucose depletion, a common nutrient stress, enables C. albicans white cells to undergo efficient sexual mating. The relative expression levels of pheromone-sensing and mating-associated genes (including STE2/3, MFA1, MFα1, FIG1, FUS1, and CEK1/2) are increased under glucose depletion conditions, while expression of mating repressors TEC1 and DIG1 is decreased. Cph1 and Tec1, factors that act downstream of the pheromone MAPK pathway, play opposite roles in regulating white cell mating as TEC1 deletion or CPH1 overexpression promotes white cell mating. Moreover, inactivation of the Cph1 repressor Dig1 increases white cell mating ~4000 fold in glucose-depleted medium relative to that in the presence of glucose. Our findings reveal that the white-to-opaque epigenetic switch may not be a prerequisite for sexual mating in C. albicans in nature.
人类真菌病原体白色念珠菌可以随机且遗传地在“白色”相和“不透明”相之间切换。不透明细胞是该物种的有性交配形式，而白色细胞被认为基本上是“无菌的”。在这里，我们报告说葡萄糖耗竭，一种常见的营养压力，使白色念珠菌白色细胞能够进行有效的性交配。在葡萄糖耗竭条件下，与交配相关的基因（包括 STE2/3、MFA1、MFα1、FIG1、FUS1 和 CEK1/2）的感受态和交配相关基因的相对表达水平增加，而交配抑制剂 TEC1 和 DIG1 的表达减少。Cph1 和 Tec1 是 MAPK 途径下游的因子，它们在调节白色细胞交配方面起着相反的作用，因为 TEC1 缺失或 CPH1 过表达促进了白色细胞交配。此外，在葡萄糖耗尽的培养基中，失活的 Cph1 抑制剂 Dig1 使白色细胞交配增加了约 4000 倍，而在存在葡萄糖的情况下则没有。我们的发现表明，白色到不透明的表观遗传开关在自然界中可能不是白色念珠菌有性交配的先决条件。
