Related Experiment Video
Updated: Nov 30, 2025
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
SWL-1 Reverses Fluconazole Resistance in Candida albicans by Regulating the Glycolytic Pathway
Xiao-Ning Li1,2, Lu-Mei Zhang1,2, Yuan-Yuan Wang3
1School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming, China.
Abstract:
Candida albicans is a ubiquitous clinical fungal pathogen. Prolonged use of the first-line antifungal agent fluconazole (FLC) has intensified fungal resistance and limited its effectiveness for the treatment of fungal infections. The combined administration of drugs has been extensively studied and applied. SWL-1 is a lignin compound derived from the Traditional Chinese Medicine Schisandra chinensis. In this study, we show that SWL-1 reverses resistance to fluconazole in C. albicans when delivered in combination, with a sharp decrease in the IC50 of fluconazole from >200 to 3.74 ± 0.25 μg/ml, and also reverses the fluconazole resistance of C. albicans in vitro, with IC50 from >200 to 5.3 ± 0.3 μg/ml. Moreover, killing kinetics curves confirmed the synergistic effects of fluconazole and SWL-1. Intriguingly, when SWL-1 was administered in combination with fluconazole in a mouse model of systemic infection, the mortality of mice was markedly decreased and fungal colonization of the kidney and lung was reduced. Further mechanistic studies showed that SWL-1 significantly decreased intracellular adenosine 5'-triphosphate (ATP) levels and inhibited the function of the efflux pump responsible for fluconazole resistance of C. albicans. Proteomic analysis of the effects of SWL-1 on C. albicans showed that several enzymes were downregulated in the glycolytic pathway. We speculate that SWL-1 significantly decreased intracellular ATP levels by hindering the glycolysis, and the function of the efflux pump responsible for fluconazole resistance of C. albicans was inhibited, resulting in restoration of fluconazole sensitivity in FLC-resistant C. albicans. This study clarified the effects and mechanism of SWL-1 on C. albicans in vitro and in vivo, providing a novel approach to overcoming fungal resistance.
Insights
SWL-1, a compound from Schisandra chinensis, effectively restores fluconazole sensitivity in Candida albicans by reducing ATP levels and inhibiting efflux pumps, offering a new strategy against fungal resistance.
Area of Science:
- Mycology
- Pharmacology
- Biochemistry
Background:
- Candida albicans is a major fungal pathogen.
- Fluconazole resistance is a growing clinical challenge.
- Combined drug therapy is a promising strategy.
Purpose of the Study:
- To investigate the efficacy of SWL-1 in combination with fluconazole against Candida albicans.
- To elucidate the mechanism by which SWL-1 overcomes fluconazole resistance.
Main Methods:
- In vitro susceptibility testing (IC50 determination) and killing kinetics.
- In vivo systemic infection mouse model.
- Intracellular ATP level measurement and efflux pump activity assays.
- Proteomic analysis of glycolytic pathways.
Main Results:
- SWL-1 significantly reduced fluconazole's IC50 in resistant C. albicans strains.
- Combination therapy with SWL-1 and fluconazole decreased mortality and fungal burden in mice.
- SWL-1 inhibited efflux pump function and decreased intracellular ATP levels.
- Proteomics revealed downregulation of glycolytic enzymes.
Conclusions:
- SWL-1 resensitizes fluconazole-resistant Candida albicans.
- The mechanism involves reduced ATP production via glycolysis inhibition and impaired efflux pump function.
- SWL-1 represents a potential therapeutic agent to combat antifungal resistance.
