BackgroundCandida albicans is an opportunistic human fungal pathogen that can cause both superficial and systemic infections, especially in immunocompromised individuals. In response to C. albicans infections, innate immune cells of the host produce and accumulate reactive oxygen species (ROS) that can lead to irreversible damage and apoptosis of fungal cells. Prior studies have identified several transcription factors involved in the oxidative stress response of C. albicans. However, a systematic study to identify transcription factors mediating the oxidative response had not been previously conducted. ResultsIn this study, we screened a comprehensive transcription factor mutant library consisting of 211 transcription factor deletion mutant strains in the presence and absence of H2O2, a potent inducer of ROS, and identified five transcription factors (Skn7, Dpb4, Cap1, Dal81 and Stp2) involved in the response to H2O2. Genome-wide transcriptional profiling revealed that H2O2 induced a discreet set of genes differentially regulated in common among the five transcription factor mutant strains identified. Functional enrichment analysis identified KEGG pathways pertaining to glycolysis/gluconeogenesis, amino sugar and nucleotide sugar metabolism, and ribosome synthesis as the most enriched pathways. Furthermore, among the most common differentially expressed genes, hexose catabolism and iron transport were the most enriched GO terms.ConclusionsOur study is the first to systematically identify and characterize transcription factors involved in the response to H2O2. Based on the transcription factors identified, we found that exposure to H2O2 modulates several downstream gene classes 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.
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