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EUKARYOTIC CELL, Aug. 2006, p. 12431251 Vol. 5, No. 8 1535-9778/06/$08.00 0 doi:10.1128/EC.00048-06

Summary: EUKARYOTIC CELL, Aug. 2006, p. 12431251 Vol. 5, No. 8
1535-9778/06/$08.00 0 doi:10.1128/EC.00048-06
Copyright 2006, American Society for Microbiology. All Rights Reserved.
Antagonism between Two Mechanisms of Antifungal Drug Resistance
James B. Anderson, Nicole Ricker, and Caroline Sirjusingh
Department of Biology, University of Toronto, 3359 Mississauga Road North, Mississauga, Ontario L5L 1C6, Canada
Received 16 February 2006/Accepted 18 May 2006
This study tested for interaction between two independently evolved mechanisms of fluconazole resistance in
Saccharomyces cerevisiae. One set of strains was from a 400-generation evolution experiment, during which the
concentration of fluconazole was increased from 16 to 256 g/ml in four increments. At 100 generations,
populations became fixed for resistance mutations in either of two transcriptional regulators, PDR1 or PDR3.
At 400 generations, replicate populations became fixed for another resistance mutation in UNK1, an unmapped
gene further increasing resistance. Another genotype used in this study came from a population placed initially
in 128 g/ml of fluconazole; this environment selects for resistance through loss of function at ERG3, resulting
in altered sterol metabolism. Mutant strains carrying PDR1r
or PDR3r
were crossed with the erg3r
strain, and the doubly mutant, haploid offspring were identified. The double-mutant strains grew less well than
the parent strains at all concentrations of fluconazole tested. In genome-wide assays of gene expression, several


Source: Anderson, James B. - Department of Ecology and Evolutionary Biology, University of Toronto


Collections: Environmental Sciences and Ecology