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Updated: May 20, 2026
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Inhibition of Candida albicans by Fluvastatin Is Dependent on pH
Martin Schmidt1, Seli Dzogbeta, Michael P Boyer
1Department of Biochemistry and Nutrition, Des Moines University, 3200 Grand Avenue, Des Moines, IA 50312, USA.
Abstract:
The cholesterol-lowering drug fluvastatin (FS) has an inhibitory effect on the growth of the pathogenic yeast Candida albicans that is dependent on the pH of the medium. At the low pH value of the vagina, FS is growth inhibitory at low and at high concentrations, while at intermediate concentrations (1-10 mM), it has no inhibitory effect. Examination of the effect of the common antifungal drug fluconazole in combination with FS demonstrates drug interactions in the low concentration range. Determination of intracellular stress and the activity of the FS target enzyme HMG-CoA reductase confirm our hypothesis that in the intermediate dose range adjustments to the sterol biosynthesis pathway can compensate for the action of FS. We conclude that the pH dependent uptake of FS across yeast membranes might make FS combination therapy an attractive possibility for treatment of vaginal C. albicans infections.
Insights
The cholesterol-lowering drug fluvastatin inhibits Candida albicans growth, particularly at vaginal pH. Combination therapy with fluconazole shows promise for treating vaginal yeast infections.
Area of Science:
- Medical Mycology
- Pharmacology
- Biochemistry
Background:
- * *Candida albicans* is a pathogenic yeast causing vaginal infections.
- * Fluvastatin (FS), a cholesterol-lowering drug, exhibits antifungal properties.
- * The efficacy of FS against *C. albicans* is influenced by environmental pH.
Purpose of the Study:
- * To investigate the pH-dependent antifungal activity of fluvastatin against *Candida albicans*.
- * To explore potential drug interactions between fluvastatin and fluconazole.
- * To elucidate the mechanisms underlying fluvastatin's efficacy and resistance.
Main Methods:
- * *In vitro* antifungal assays assessing fluvastatin's effect on *C. albicans* growth at varying pH levels.
- * Evaluation of fluvastatin and fluconazole combination therapy.
- * Measurement of intracellular stress markers and HMG-CoA reductase activity.
Main Results:
- * Fluvastatin demonstrated pH-dependent inhibition of *C. albicans* growth, with efficacy at low and high pH but not intermediate concentrations (1-10 mM).
- * Synergistic drug interactions were observed between fluvastatin and fluconazole at low concentrations.
- * Sterol biosynthesis pathway adjustments compensated for fluvastatin's action at intermediate concentrations, as indicated by HMG-CoA reductase activity and stress levels.
Conclusions:
- * pH-dependent membrane uptake of fluvastatin influences its antifungal activity.
- * Fluvastatin in combination with fluconazole presents a potential therapeutic strategy for vaginal *C. albicans* infections.
- * Understanding the mechanisms of resistance can guide the development of novel antifungal treatments.
