title: Transcriptional response to fluconazole and amphotericin B in Candida albicans biofilms.
abstract: Biofilm formation is often associated with persistent Candida albicans infections. Treatment of these infections is difficult, since sessile C. albicans cells show increased resistance towards antifungal agents. The molecular mechanisms behind biofilm resistance in C. albicans are not yet understood. In the present study, we investigated the transcriptional response in young and mature in vitro-grown biofilms after a short and longer exposure time to high doses of fluconazole or amphotericin B. Treatment of biofilms with high doses of antifungal agents resulted in a drug-specific transcriptional response. Exposure of biofilms to fluconazole induced upregulation of genes encoding enzymes involved in ergosterol biosynthesis (ERG1, ERG3, ERG11 and ERG25). Treatment of biofilms with amphotericin B resulted in an overexpression of KRE1 and SKN1, two genes encoding proteins involved in beta-1,6-glucan biosynthesis. Our data indicate that sessile C. albicans cells show controlled regulation of gene expression, as they quickly mount a drug-specific transcriptional response in the presence of high doses of antifungal agents. These transcriptional changes suggest upregulation of ergosterol biosynthesis (fluconazole) and upregulation of beta-1,6-glucan biosynthesis (amphotericin B) in sessile C. albicans cells that might contribute to a resistant biofilm phenotype.
authors.affiliation: Laboratory of Pharmaceutical Microbiology, Ghent University, Harelbekestraat 72, B-9000, Ghent, Belgium. heleen.nailis@ugent.be
authors.forename: Heleen
authors.initials: H
authors.lastname: Nailis
authors.forename: Davy
authors.initials: D
authors.lastname: Vandenbosch
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nelis
authors.forename: Tom
authors.initials: T
authors.lastname: Coenye
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D000666:Amphotericin B; D015725:Fluconazole