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Updated: Jul 5, 2026
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Integrative Phosphoproteomic and Proteomic Analysis of Candida albicans Exposed to Oxidative Stress
Víctor Arribas1, Ana Borrajo1, María Luisa Hernáez2
1Department of Microbiology and Parasitology, Faculty of Pharmacy, Complutense University of Madrid (UCM), 28040 Madrid, Spain.
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.
Insights
Candida albicans, a WHO high-priority pathogen, faces limited treatments. This study used DDA-MS to uncover new antifungal targets by analyzing protein and phosphorylation changes during oxidative stress response.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Candida albicans is a WHO-identified high-priority pathogen causing invasive fungal infections.
- Limited antifungal treatments necessitate the discovery of novel therapeutic targets.
- Oxidative stress significantly impacts C. albicans survival and virulence.
Purpose of the Study:
- To investigate the phosphoproteomics and proteomics of C. albicans under oxidative stress.
- To identify key proteins and phosphorylation events involved in the late-stage stress response.
- To discover new potential antifungal targets and understand their mechanisms.
Main Methods:
- Utilized Data-Dependent Acquisition Mass Spectrometry (DDA-MS) technology.
- Analyzed both protein abundance and phosphorylation changes.
- Applied 10 mM H2O2 treatment for 200 minutes to induce oxidative stress.
Main Results:
- Identified and quantified significant changes in protein and phosphoprotein levels.
- Discovered novel phosphorylation sites in kinases and transcription factors.
- Cdc5-reduced phosphorylation linked to G2 cell cycle arrest; Kis1 involved in ROS scavenging; Gzf3-decreased phosphorylation crucial for survival.
Conclusions:
- DDA-MS is effective for identifying novel proteins and phosphorylation sites in C. albicans stress response.
- Specific kinases (Cdc5, Kis1) and transcription factors (Gzf3) play critical roles in oxidative stress adaptation.
- Findings provide potential new targets for antifungal drug development against C. albicans.
