title: Triclosan antagonizes fluconazole activity against Candida albicans.
abstract: Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg/L. However, at subinhibitory concentrations (0.5-2 mg/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Δ strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes.
authors.affiliation: Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: Higgins
authors.forename: E
authors.initials: E
authors.lastname: Pinjon
authors.forename: H N
authors.initials: HN
authors.lastname: Oltean
authors.forename: T C
authors.initials: TC
authors.lastname: White
authors.forename: S L
authors.initials: SL
authors.lastname: Kelly
authors.forename: C M
authors.initials: CM
authors.lastname: Martel
authors.forename: D J
authors.initials: DJ
authors.lastname: Sullivan
authors.forename: D C
authors.initials: DC
authors.lastname: Coleman
authors.forename: G P
authors.initials: GP
authors.lastname: Moran
mesh_terms: D000935:Antifungal Agents / Q000037:antagonists & inhibitors*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D004336:Drug Antagonism; D005227:Fatty Acids / Q000096:biosynthesis; D015725:Fluconazole / Q000037:antagonists & inhibitors*; D005656:Fungal Proteins / Q000096:biosynthesis; D025301:Hyphae / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D013045:Species Specificity; D014260:Triclosan / Q000009:adverse effects*
chemical_list: D000935:Antifungal Agents; C094693:CDR1 protein, Candida albicans; D005227:Fatty Acids; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D014260:Triclosan; D015725:Fluconazole