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Antimicrobial Agents and Chemotherapy, July 2003, p. 2366-2369, Vol. 47, No. 7
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.7.2366-2369.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Jacob M. Hornby, Bessie W. Kebaara, and Kenneth W. Nickerson*

School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588-0666

Received 12 February 2003/ Returned for modification 3 March 2003/ Accepted 14 April 2003

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.

* Corresponding author. Mailing address: School of Biological Sciences, University of Nebraska, Lincoln, NE 68588-0666. Phone: (402) 472-2253. Fax: (402) 472-8722. E-mail: knickerson1{at}unl.edu.

Antimicrobial Agents and Chemotherapy, July 2003, p. 2366-2369, Vol. 47, No. 7
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.7.2366-2369.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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