Related Experiment Video
Updated: Jul 7, 2025
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Systematic identification and characterization of five transcription factors mediating the oxidative stress response
Yingchao Cui1, Daosheng Wang1, Clarissa J Nobile2
1Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
Insights
This study systematically identified five key transcription factors (Skn7, Dpb4, Cap1, Dal81, Stp2) crucial for Candida albicans's response to oxidative stress from hydrogen peroxide (H2O2). Findings reveal H2O2 impacts fungal metabolism and virulence pathways.
Area of Science:
- Mycology
- Molecular Biology
- Immunology
Background:
- Candida albicans is an opportunistic pathogen causing infections, especially in immunocompromised individuals.
- Host immune cells produce reactive oxygen species (ROS), like hydrogen peroxide (H2O2), to combat C. albicans, inducing fungal cell damage and apoptosis.
- While some transcription factors mediating oxidative stress response are known, a systematic identification was lacking.
Purpose of the Study:
- To systematically screen and identify transcription factors critical for the oxidative stress response in Candida albicans.
- To characterize the transcriptional changes and affected pathways in response to H2O2 exposure mediated by these transcription factors.
Main Methods:
- A comprehensive transcription factor mutant library (211 strains) was screened for H2O2 sensitivity.
- Genome-wide transcriptional profiling was performed on identified sensitive mutant strains.
- Functional enrichment analysis (KEGG pathways, GO terms) was used to interpret gene expression data.
Main Results:
- Five transcription factors (Skn7, Dpb4, Cap1, Dal81, Stp2) were identified as sensitive to H2O2.
- H2O2 induced distinct gene expression patterns in these mutant strains, significantly enriching pathways like glycolysis/gluconeogenesis and metabolism.
- Key enriched GO terms included hexose catabolism and iron transport, indicating significant metabolic and physiological shifts.
Conclusions:
- This study provides the first systematic identification and characterization of transcription factors involved in the H2O2 oxidative stress response in C. albicans.
- The findings highlight the modulation of fungal virulence-associated genes by H2O2, offering new insights into C. albicans's cellular processes and stress adaptation mechanisms.
