Transcription factor Hap2p regulates antioxidant stress responses to maintain miconazole resistance in .

Acquired resistance in brings about a serious challenge to the clinical application of azoles, so it is urgent to elucidate the mechanisms of azole resistance to improve the therapeutic efficiency. In the aim of searching for the potential targets mediating fluconazole resistance, we screened a mutant library of 48 transcription factor deletion strains. The screening results showed that mutants were significantly more susceptible to azoles, especially to miconazole (MCZ). Under MCZ treatment, the intracellular reactive oxygen species (ROS) were significantly higher in mutants compared to the control strain SN250. The addition of antioxidants reversed the MCZ-sensitive phenotype caused by the deletion of . Consistently, the expression of antioxidases responsible for scavenging ROS was shown to decrease in mutants, suggesting that the transcription factor Hap2p is involved in the regulation of oxidative stress responses in . In addition, deficiency also resulted in impaired mitochondrial function and affected cellular energy supply, which may be related to the iron deficiency regulated by HAP complex. disruption also decreased efflux-mediated resistance of , as demonstrated by a significant decrease in Cdr1p expression and a slight decrease in Mdr1p expression in strains under the action of MCZ. The above results indicate that the transcription factor Hap2p was required for the resistance of to azoles, which could provide a new strategy to solve the clinical azoles resistance.