Function of the phosphatidylinositol synthase Pis1 in maintenance of endoplasmic reticulum function and pathogenicity in Candida albicans.

ABSTRACT

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.