The Transcription Factor Sfp1 Regulates the Oxidative Stress Response in Candida albicans

Area of Science:

• Microbiology
• Molecular Biology
• Mycology

Background:

• * *Candida albicans* is a common human commensal that can cause opportunistic infections, particularly in immunocompromised individuals.
• * Antifungal drug resistance and increasing immunocompromised populations highlight the need to understand *C. albicans* pathogenesis.
• * Reactive oxygen species (ROS) are crucial in host defense and antifungal drug action, making antioxidative capacity vital for *C. albicans* survival.

Purpose of the Study:

• * To investigate the role of the zinc finger transcription factor Sfp1 in the oxidative stress response of *Candida albicans*.
• * To determine how Sfp1 deletion affects the fungus's resistance to oxidative stress and host immune cells.

Main Methods:

• * Generation and characterization of a *sfp1*-deleted mutant of *C. albicans*.
• * Assessment of oxidative stress response pathways, including MAPK Hog1 phosphorylation and *CAP1* gene expression.
• * Measurement of antioxidant gene expression, total antioxidant capacity, glutathione content, and enzyme activities (glutathione peroxidase, superoxide dismutase).
• * Evaluation of mutant resistance to macrophage killing and ROS-generating antifungal drugs.

Main Results:

• * The *sfp1*-deleted mutant showed increased resistance to oxidants and macrophage killing compared to wild-type *C. albicans*.
• * Deletion of *sfp1* led to an active oxidative stress response, evidenced by Hog1 phosphorylation and high *CAP1* expression.
• * The mutant exhibited elevated expression of antioxidant genes, resulting in higher total antioxidant capacity, glutathione levels, and enzyme activities.
• * The *sfp1*-deleted mutant demonstrated resistance to both macrophage-mediated killing and ROS-inducing antifungal drugs.

Conclusions:

• * Sfp1 plays a significant role in regulating the oxidative stress response in *Candida albicans*.
• * Deletion of Sfp1 enhances *C. albicans*'s ability to cope with oxidative stress, increasing its virulence and resistance to antifungal treatments.
• * Findings provide new insights into the regulatory mechanisms governing *C. albicans* oxidative stress survival and pathogenesis.