Open AccessAn A643V Amino Acid Substitution in Upc2p Contributes to Azole Resistance in Well-Characterized Clinical Isolates of Candida albicans
Author(s) -
Samantha J. Hoot,
Adam R. Smith,
Ryan P. Brown,
Theodore C. White
Publication year - 2011
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00995-10
Subject(s) - azole , candida albicans , biology , gene , corpus albicans , ergosterol , microbiology and biotechnology , drug resistance , genetics , antifungal , biochemistry
TheCandida albicans Upc2p transcription factor regulatesERG11 , 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 overexpressedERG11 . Azole susceptibility, ergosterol levels, and expression ofERG genes were elevated in the A643V clinical isolates and in reconstructed strains.