Integrative Phosphoproteomic and Proteomic Analysis of Candida albicans Exposed to Oxidative Stress.

Abstract

Candida albicans is an opportunistic pathogen, which has recently been included in the high-priority list of pathogenic fungi by the World Health Organization (WHO). The scarce arsenal available to treat such invasive fungal infections makes the discovery of new antifungal targets an important task. This study utilizes DDA-MS technology to investigate both the phosphoproteomics and proteomics of C. albicans during its late-stage response to oxidative stress induced by H₂O₂, aiming to identify key proteins involved. Phosphorylation, as an important post-translational modification, plays a crucial role in the ability of C. albicans to survive oxidative stress. Our study enabled the identification and quantification of important changes in both protein abundance and phosphorylation events across multiple proteins following a 200 min 10 mM H₂O₂ treatment. The use of the DDA-MS approach allowed for the identification of new actors in the response to oxidative stress. Novel phosphorylation sites were identified in kinases and transcription factors. Regarding protein kinases, Cdc5-reduced phosphorylation may mediate a transient G2 cell cycle arrest, while Kis1─the regulatory β-subunit of Snf1 kinase─might play a role in ROS scavenging following oxidative stress. In terms of transcription factors, Gzf3-decreased phosphorylation was essential for cell survival and ROS detoxification after oxidative stress.