Atractylodin Enhances the Efficacy of Fluconazole Against Fluconazole-Resistant C. albicans by Promoting ROS

Jinyun Song1, Juan Wang2, Sijia Hu2

  • 1Department of Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China.

Mycopathologia
|April 2, 2026
PubMed

Insights

Atractylodin (ATL) combined with fluconazole (FCZ) shows significant synergy against drug-resistant Candida albicans. This combination restores FCZ sensitivity by increasing reactive oxygen species and inhibiting virulence factors like biofilms.

Area of Science:

  • Mycology
  • Pharmacology
  • Biochemistry

Background:

  • Drug-resistant Candida albicans poses a major threat to fluconazole therapy.
  • Restoring sensitivity to existing antifungal drugs is a critical therapeutic goal.

Purpose of the Study:

  • To investigate the synergistic antifungal efficacy of Atractylodin (ATL) and fluconazole (FCZ) against fluconazole-resistant Candida albicans.
  • To elucidate the underlying mechanisms of this synergistic interaction.

Main Methods:

  • Fractional Inhibitory Concentration Index (FICI) for synergy assessment.
  • Scanning electron microscopy and reactive oxygen species (ROS) assays.
  • Transcriptome sequencing and microbial metabolomics.
  • Evaluation of virulence factors including hyphae and biofilm formation.

Main Results:

  • ATL demonstrated significant synergy with FCZ against resistant C. albicans, reducing FCZ minimum inhibitory concentrations (MICs) by 32-64 times (FICI < 0.5).
  • The combination induced cell damage and significantly increased ROS levels, with upregulation of ROS-related genes (SOD2, HSP90) and downregulation of cell wall genes (CHS7, CWH8).
  • ATL and FCZ synergistically inhibited hyphae and biofilm formation, linked to downregulated key metabolites in glycolysis, TCA cycle, amino acid, lipid, and nucleotide metabolism.

Conclusions:

  • The combination of ATL and FCZ exhibits a potent synergistic antifungal effect against fluconazole-resistant C. albicans, likely via ROS induction.
  • Metabolic alterations contribute to the inhibition of biofilm formation, suggesting a multi-faceted mechanism.
  • Atractylodin shows promise as a sensitizer to enhance clinical antifungal therapy.

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