Systematic identification and characterization of five transcription factors mediating the oxidative stress response in Candida albicans

Abstract

Candida albicans is an opportunistic human fungal pathogen that causes superficial and systemic infections, particularly in immunocompromised individuals. In response to C. albicans infection, innate immune cells of the host produce and accumulate reactive oxygen species (ROS), which can lead to irreversible damage and apoptosis of fungal cells. Several transcription factors involved in this oxidative stress response have been identified; however, a systematic study to identify the transcription factors that mediate the oxidative stress response has not yet been conducted. Here, we screened a comprehensive transcription factor mutant library consisting of 211 transcription factor deletion mutant strains in the presence and absence of hydrogen peroxide (H₂O₂), a potent ROS inducer, and identified five transcription factors (Skn7, Dpb4, Cap1, Dal81, and Stp2) that are sensitive to H₂O₂. Genome-wide transcriptional profiling revealed that H₂O₂ induces a discrete set of differentially regulated genes among the five identified transcription factor mutant strains. Functional enrichment analysis identified KEGG pathways pertaining to glycolysis/gluconeogenesis, amino sugar and nucleotide sugar metabolism, and ribosome synthesis as the most enriched pathways. GO term analysis of the top common differentially expressed genes among the transcription factor mutant strains identified hexose catabolism and iron transport as the most enriched GO terms upon exposure to H₂O₂. This study is the first to systematically identify and characterise the transcription factors involved in the response to H₂O₂. Based on our transcriptional profiling results, we found that exposure to H₂O₂ modulates several downstream genes involved in fungal virulence. Overall, this study sheds new light on the metabolism, physiological functions, and cellular processes involved in the H₂O₂-induced oxidative stress response in C. albicans.

Keywords: Candida albicans; Hydrogen peroxide; Oxidative stress response; ROS; Transcription factors; Transcriptional profiling.