title: An A643V amino acid substitution in Upc2p contributes to azole resistance in well-characterized clinical isolates of Candida albicans.
abstract: The Candida albicans Upc2p transcription factor regulates ERG11, encoding the target of azole drugs. Gain-of-function mutations that contribute to resistance were recently identified in a series of sequential clinical isolates (N. Dunkel, T. T. Liu, K. S. Barker, R. Homayouni, J. Morschhauser, and P. D. Rogers, Eukaryot. Cell 7:1180-1190, 2008). In the present study, UPC2 was sequenced from a matched set of 17 isolates. An A643V substitution was present in all of the isolates in the series that overexpressed ERG11. Azole susceptibility, ergosterol levels, and expression of ERG genes were elevated in the A643V clinical isolates and in reconstructed strains.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Hoot
authors.forename: Adam R
authors.initials: AR
authors.lastname: Smith
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Brown
authors.forename: Theodore C
authors.initials: TC
authors.lastname: White
mesh_terms: D019943:Amino Acid Substitution; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics*; D004875:Ergosterol / Q000096:biosynthesis / Q000235:genetics; D015725:Fluconazole / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008826:Microbial Sensitivity Tests; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D015534:Trans-Activators; D015725:Fluconazole; D004875:Ergosterol