Farnesol Biosynthesis in Candida albicans: Cellular Response to Sterol Inhibition by Zaragozic Acid B

Authors

Jacob M. Hornby, University of Nebraska-LincolnFollow
Bessie W. Kebaara, University of Nebraska-LincolnFollow
Kenneth W. Nickerson, University of Nebraska-LincolnFollow

Date of this Version

7-1-2003

Comments

Published in ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, July 2003, p. 2366–2369 Vol. 47, No. 7 2003. Copyright © 2003, American Society for Microbiology. Used by permission.

Abstract

The dimorphic fungus Candida albicans produces farnesol as a quorum-sensing molecule that regulates cellular morphology. The biosynthetic origin of farnesol has been resolved by treating these cells with zaragozic acid B, a potent inhibitor of squalene synthase in the sterol biosynthetic pathway. Treatment with zaragozic acid B leads to an eightfold increase in the amount of farnesol produced by C. albicans. Furthermore, C. albicans cell extracts contain enzymatic activity to convert [³H]farnesyl pyrophosphate to [³H]farnesol. Many common antifungal antibiotics (e.g., zaragozic acids, azoles, and allylamines) target steps in sterol biosynthesis. We suggest that the fungicidal activity of zaragozic acid derives in large part from the accumulation of farnesol that accompanies the inhibition of sterol biosynthesis.