Farnesol biosynthesis in Candida albicans

Cellular response to sterol inhibition by zaragozic acid B

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

Research output: Contribution to journalArticle

83 Citations (Scopus)

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

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Farnesol
Sterols
Candida albicans
Farnesyl-Diphosphate Farnesyltransferase
Allylamine
Quorum Sensing
Azoles
Acids
Antifungal Agents
Biosynthetic Pathways
Cell Extracts
Fungi
zaragozic acid B

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Farnesol biosynthesis in Candida albicans : Cellular response to sterol inhibition by zaragozic acid B. / Hornby, Jacob M.; Kebaara, Bessie W.; Nickerson, Kenneth.

In: Antimicrobial Agents and Chemotherapy, Vol. 47, No. 7, 01.07.2003, p. 2366-2369.

Research output: Contribution to journalArticle

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