Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
Sci Rep. 2022 May 9;12(1):7574. doi: 10.1038/s41598-022-11682-y.
Candida albicans, a commensal and opportunistic pathogen, undergoes apoptosis in response to various stimuli, including hydrogen peroxide, acetic acid, and antifungal agents. Apoptotic processes are highly conserved among mammals, plants, and fungi, but little is known about the apoptosis-regulating factors in C. albicans. In this study, C. albicans homologs of the putative apoptosis factors were identified by database screening followed by overexpression analysis. CaNma111, a homolog of the pro-apoptotic mammalian HtrA2/Omi, and CaYbh3, a homolog of BH3-only protein, yielded increased apoptotic phenotypes upon overexpression. We showed that CaNma111 and CaYbh3 functions as pro-apoptotic regulators by examining intracellular ROS accumulation, DNA end breaks (TUNEL assay), and cell survival in Canma111/Canma111 and Caybh3/Caybh3 deletion strains. We found that the protein level of CaBir1, an inhibitor-of-apoptosis (IAP) protein, was down-regulated by CaNma111. Interestingly, the Canma111/Canma111 and Caybh3/Caybh3 deletion strains showed hyperfilamentation phenotypes and increased virulence in a mouse infection model. Together, our results suggest that CaNma111 and CaYbh3 play key regulatory roles in the apoptosis and virulence of C. albicans.
白色念珠菌是一种共生和机会性病原体，它会对各种刺激物（包括过氧化氢、乙酸和抗真菌剂）作出凋亡反应。凋亡过程在哺乳动物、植物和真菌中高度保守，但关于白色念珠菌中凋亡调节因子知之甚少。在这项研究中，通过数据库筛选和过表达分析，鉴定出了白色念珠菌中假定凋亡因子的同源物。CaNma111 是促凋亡哺乳动物 HtrA2/Omi 的同源物，CaYbh3 是 BH3 仅蛋白的同源物，过表达时表现出增加的凋亡表型。通过检测细胞内 ROS 积累、DNA 末端断裂（TUNEL 检测）和 Canma111/Canma111 和 Caybh3/Caybh3 缺失菌株中的细胞存活，我们表明 CaNma111 和 CaYbh3 作为促凋亡调节剂发挥作用。我们发现，凋亡抑制剂（IAP）蛋白 CaBir1 的蛋白水平被 CaNma111 下调。有趣的是，Canma111/Canma111 和 Caybh3/Caybh3 缺失菌株表现出过度丝状化表型，并在小鼠感染模型中增加了毒力。总之，我们的结果表明，CaNma111 和 CaYbh3 在白色念珠菌的凋亡和毒力中发挥关键调节作用。
