Investigating the role of osmotic stress on fungal immune evasion

Candida albicans is a commensal fungus of the urogenital and GI tract. However in immunocompromised hosts and those with microbiome dysbiosis, C. albicans can outcompete the immune system and break through physical barriers causing infections. Adaptations to host environmental stresses are vital for maintaining pathogenicity and survival. During systemic infections, C. albicans targets the kidney, where the pathogen is exposed to osmotic stress. Here, we investigate how adaptations of C. albicans to osmotic stress impacts the host-pathogen interaction. C. albicans underwent osmotic stress induced immune evasion, however this phenotype was not observed in all clinical isolates. Further investigation found that osmotic stress induced immune evasion is dependent on the inactivation of RNA interference. Osmotic stress induced immune evasion was also observed in Candida tropicalis, which has previously been described as RNAi inactive. AP-1 like transcription factor Cap1, known for playing a role in C. albicans oxidative stress and combinatorial stress response, was found to be required for osmotic stress induced immune evasion. Using DESeq2 analysis, differentially regulated Cap1 dependent genes were identified, and AQY1, HWP1 and EBP1 were implicated in the osmotic stress induced immune evasion. Our findings show that osmotic stress induces immune evasion in C. albicans cells that lack RNAi functionality occurs in a Cap1-dependent manner.