Quorum sensing in Candida albicans: Probing farnesol's mode of action with 40 natural and synthetic farnesol analogs

Roman Shchepin, Jacob M. Hornby, Erin Burger, Timothy Niessen, Patrick Dussault, Kenneth W. Nickerson

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Abstract

The dimorphic fungus Candida albicans produces extracellular farnesol (3,7,11-trimethyl-2,6,10-dodecatriene-1-ol) which acts as a quorum-sensing molecule (QSM) to suppress filamentation. Of four possible geometric isomers of farnesol, only the E,E isomer possesses QSM activity. We tested 40 natural and synthetic analogs of farnesol for their activity in an N-acetylglucosamine-induced differentiation assay for germ tube formation (GTF). Modified structural features include the head group, chain length, presence or absence of the three double bonds, substitution of a backbone carbon by S, O, N, and Se heteroatoms, presence or absence of a 3-methyl branch, and the bulkiness of the hydrophobic tail. Of the 40 compounds, 22 showed QSM activity by their ability to reduce GTF by 50%. However, even the most active of the analogs tested had only 7.3% of the activity of E,E-farnesol. Structure-activity relationships were examined in terms of the likely presence in C. albicans of a farnesol binding receptor protein.

Original languageEnglish (US)
Pages (from-to)743-750
Number of pages8
JournalChemistry and Biology
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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