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Updated: Jan 18, 2026

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis

Published on: March 19, 2019

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

Yulin Qin1,2,3, Quanzhen Lv3, Hongtao Xu3

  • 1Institute of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Mycology
|September 12, 2025
PubMed

Insights

The transcription factor Hap2p is crucial for azole resistance in Candida albicans. Deleting HAP2 increases susceptibility to antifungals like miconazole by affecting oxidative stress and efflux pumps.

Area of Science:

  • Mycology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Azole antifungal resistance in *Candida albicans* poses a significant clinical challenge.
  • Understanding azole resistance mechanisms is vital for improving therapeutic strategies.
  • Transcription factors are key regulators of fungal gene expression and adaptation.

Purpose of the Study:

  • To identify potential targets involved in fluconazole resistance in *Candida albicans*.
  • To investigate the role of transcription factor Hap2p in azole resistance.

Main Methods:

  • Screening of a *Candida albicans* mutant library with 48 transcription factor deletions.
  • Assessing azole susceptibility, particularly to miconazole (MCZ), in *hap2Δ/Δ* mutants.
  • Measuring intracellular reactive oxygen species (ROS) levels and antioxidant enzyme expression.
  • Evaluating mitochondrial function, cellular energy supply, and efflux pump expression (Cdr1p, Mdr1p).

Main Results:

  • *hap2Δ/Δ* mutants exhibited significantly increased susceptibility to azoles, especially miconazole.
  • Miconazole treatment led to elevated intracellular ROS in *hap2Δ/Δ* mutants, which was reversed by antioxidants.
  • Hap2p deficiency decreased the expression of ROS-scavenging antioxidases, impairing oxidative stress response.
  • Hap2p deficiency also resulted in impaired mitochondrial function and reduced expression of efflux pumps Cdr1p and Mdr1p.

Conclusions:

  • The transcription factor Hap2p is essential for azole resistance in *Candida albicans*.
  • Hap2p regulates oxidative stress responses, mitochondrial function, and efflux-mediated resistance.
  • Targeting Hap2p could offer a novel strategy to overcome clinical azole resistance in *C. albicans*.
Keywords:
Candida albicansHap2panti-oxidative stressazole susceptibilitymitochondrial function

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