Farnesol biosynthesis in Candida albicans: Cellular response to sterol inhibition by zaragozic acid B

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

Research output: Contribution to journalArticle

86 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2366-2369
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume47
Issue number7
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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