Oxidative stress responses in human fungal pathogens: a review of molecular mechanisms

Fungal infections represent a major global health challenge due to their high morbidity and mortality and calling for innovative therapeutic approaches. Effective redox regulation is essential for fungal pathogens to maintain viability and virulence within the oxidative environment of the host. Key components of the fungal antioxidant network include superoxide dismutases, catalases, glutathione- and thioredoxin-dependent systems, and enzymes involved in trehalose metabolism. In pathogens such as Candida albicans and Cryptococcus neoformans, disruption of specific antioxidant factors increases susceptibility to oxidative stress and markedly reduces virulence. Moreover, redox-sensing transcription factors such as Yap1, Cap1, and CnYap1 play central roles in modulating antioxidant response during host interaction and antifungal exposure. Cap1 is critical for oxidative stress tolerance and immune evasion in C. albicans, whereas CnYap1 is required for resistance to oxidative stress and fluconazole in C. neoformans. In addition, antifungals such as amphotericin B increase ROS load, demanding efficient antioxidant responses from fungal cells. Collectively, these findings highlight oxidative stress response pathways as a promising therapeutic target for invasive fungal infections. Targeting key elements of redox sensing and detoxification pathways, such as transcriptional regulators and antioxidant enzymes, could increase antifungal activity, compromise fungal resistance mechanisms, and ultimately improve clinical outcomes.