Related Experiment Video
Updated: Apr 4, 2026

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
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.
Abstract:
The rise of resistant Candida albicans (C. albicans) poses a significant challenge to fluconazole (FCZ) therapy. Restoring FCZ sensitivity offers a therapeutic strategy for resistant isolates. Atractylodin (ATL), a polyacetylene from Atractylodis Rhizoma, possesses antifungal activity. This study aimed to investigate the synergistic efficacy of ATL and FCZ against drug-resistant C. albicans and explore the underlying mechanisms. Fractional inhibitory concentration index (FICI) for synergy evaluation, scanning electron microscopy, and reactive oxygen species (ROS) production were conducted to investigate the antifungal effect on FCZ-resistant C. albicans 04. Transcriptome sequencing was performed to confirm the differentially expressed genes between ATL + FCZ and FCZ treatment. Meanwhile, the effect of ATL and FCZ combination on the virulence factors was explored through hyphae formation and antibiofilm experiment. Microbial metabolomics was used to identify the mechanism of the synergistic biofilm inhibition. ATL had significant synergistic effect with FCZ against FCZ-resistant C. albicans, and reduced the MICs of FCZ by 32 or 64 times, with FICI < 0.5. The ATL and FCZ combination caused damage to C. albicans cells and significantly increased ROS levels. Transcriptome sequencing also revealed that the gene involved in ROS inculding SOD2 and HSP90 were upregulated, while cell wall-related genes CHS7 and CWH8 were downregulated. Meanwhile, ATL strongly synergized with FCZ against hyphae and biofilm formation of FCZ resistant C. albicans. Metabolomics revealed that key metabolites (e.g., glucose 6-phosphate, isocitric acid, most lipid species, leucylproline, 3'-adenylic acid) were significantly downregulated in the ATL + FCZ combination group versus control and monotherapies. In conclusion, we demonstrated for the first time that the combination of ATL and FCZ may produce a synergistic antifungal effect against FCZ-resistant C. albicans, potentially through the induction of ROS accumulation. The alterations of metabolites mainly involved in glycolysis, TCA cycle, amino acids, lipid, and nucleotide metabolism may be responsible for the inhibition of C. albicans biofilm formation. ATL exhibited a strong synergist with FCZ against C. albicans, highlighting the potential of ATL as a sensitizer in clinical antifungal therapy.
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.
Related Concept Videos
Antifungal Agents
Inhibitors of Bacterial DNA Synthesis
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

