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Research Letters in Biochemistry
Volume 2009, Article ID 151424, 4 pages
http://dx.doi.org/10.1155/2009/151424
Research Letter

Inhibition of Candida albicans by Fluvastatin Is Dependent on pH

Department of Biochemistry and Nutrition, Des Moines University, 3200 Grand Avenue, Des Moines, IA 50312, USA

Received 1 June 2009; Accepted 13 July 2009

Academic Editor: Edna S. Kaneshiro

Copyright © 2009 Martin Schmidt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.