Endoplasmic Reticulum Stress-Induced Autophagy Changes Pathogenicity Of Candida Albicans

Inositol-requiring enzyme 1 (IRE1), an endoplasmic reticulum (ER) - resident transmembrane protein, serves as an ER stress sensor. The effects of IRE1-related ER stress on autophagy and pathogenicity of C. albicans were investigated. The expressions of ire1 and the reactive oxygen species (ROS) level in planktonic cells and biofilm of C. albicans were compared respectively. The ire1 mutant strain (ire1Δ/Δ) was constructed and after being treated with different concentrations of ER stress inducer (tunicamycin, TM), the stress levels were examined, the morphological changes were observed, the expressions of the autophagy-related (ATG) genes and proteins were analyzed, and the autophagosomes were detected. The survival rate and drug susceptibility were further evaluated before and after rapamycin (an autophagy activator) treatment. The expression of ire1 was significantly up-regulated in biofilm (P < 0.05), as well as in resistance strain, while the ROS level was lower in biofilm than in planktonic cells (P < 0.01). After treatment with TM, the stress levels of ire1Δ/Δ increased; there were more wrinkles on the cell surface and less hyphae density of ire1Δ/Δ; further, the expressions of the ATG genes and proteins decreased in ire1Δ/Δ, along with only broken ER lack of autophagosomes. The survival rate and drug resistance decreased of ire1Δ/Δ, while autophagy activated by rapamycin rescued its survival and increased the resistance to antifungal agents. IRE1-related ER stress-induced autophagy was involved in the pathogenicity of C. albicans, which was a promising therapeutic target for C. albicans-related infections.