Liu Yingzheng, Ma Congcong, Mao Xiaolong, Zhao Qiang, Yu Dixiong, Yang Li, Li Mingchun
Key Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Nankai University, 94 Weijin Rd., Tianjin 300071, China.
Key Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Nankai University, 94 Weijin Rd., Tianjin 300071, China.
Fungal Genet Biol. 2022 May;160:103674. doi: 10.1016/j.fgb.2022.103674. Epub 2022 Feb 26.
Candida albicans is a common conditional pathogenic fungus in the human body, and its infections have received widespread attention in recent years. Phosphatidylinositol and its derivatives have significant regulatory effects on many physiological processes, such as cell metabolism and growth. In this study, we identified and studied the function of the phosphatidylinositol synthase Pis1 in Candida albicans. The protein has a conserved CAPT motif and multiple transmembrane domains. GFP tagging revealed that Pis1 was located at the endoplasmic reticulum (ER). The PIS1 knockout mutant was constructed using an induction system regulated by the MET3 promoter. Growth assays showed that PIS1 is an essential gene for normal growth of Candida albicans. Overexpression of PIS1 led to high sensitivity to both ER stress and cell wall stress, and down-regulated expression of the genes involved in ER stress response and maintenance of cell wall integrity. Interestingly, PIS1 overexpression enhanced secretion of the extracellular hydrolases. Virulence assays further revealed that PIS1 overexpression increased the fungal virulence, leading to quicker death of the fungus-infected mice and more severe fungal burden in the mouse kidneys. In summary, Pis1 is involved in ER stress response, maintenance of cell wall integrity, and pathogenicity of Candida albicans.
白色念珠菌是人体中一种常见的条件致病真菌，其感染近年来受到广泛关注。磷脂酰肌醇及其衍生物对许多生理过程具有重要的调节作用，如细胞代谢和生长。在本研究中，我们鉴定并研究了白色念珠菌中磷脂酰肌醇合酶Pis1的功能。该蛋白具有保守的CAPT基序和多个跨膜结构域。绿色荧光蛋白标记显示Pis1定位于内质网（ER）。使用由MET3启动子调控的诱导系统构建了PIS1基因敲除突变体。生长试验表明PIS1是白色念珠菌正常生长所必需的基因。PIS1的过表达导致对内质网应激和细胞壁应激均高度敏感，并下调了参与内质网应激反应和维持细胞壁完整性的基因的表达。有趣的是，PIS1的过表达增强了细胞外水解酶的分泌。毒力试验进一步表明，PIS1的过表达增加了真菌的毒力，导致感染真菌的小鼠更快死亡，小鼠肾脏中的真菌负荷更严重。总之，Pis1参与了白色念珠菌的内质网应激反应、细胞壁完整性维持和致病性。
