title: Quorum sensing in Candida albicans: probing farnesol's mode of action with 40 natural and synthetic farnesol analogs.
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.
authors.affiliation: Department of Chemistry, University of Nebraska, Lincoln, NE 68588, USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Shchepin
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hornby
authors.forename: Erin
authors.initials: E
authors.lastname: Burger
authors.forename: Timothy
authors.initials: T
authors.lastname: Niessen
authors.forename: Patrick
authors.initials: P
authors.lastname: Dussault
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Nickerson
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005204:Farnesol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure
chemical_list: D000935:Antifungal Agents; D005204:Farnesol