Pdr5 is a major ATP-binding cassette (ABC) multidrug transporter regarded as the founding member of a fungal subfamily of clinically significant efflux pumps. When these proteins are overexpressed, they confer broad-spectrum ultraresistance. To better understand the evolution of these proteins under selective pressure, we exposed a Saccharomyces cerevisiae yeast strain already overexpressing Pd...

Multiple or pleiotropic drug resistance in the yeast Saccharomyces cerevisiae requires the expression of several ATP binding cassette transporter-encoding genes under the control of the zinc finger-containing transcription factor Pdrlp. The ATP binding cassette transporter-encoding genes regulated by Pdrlp include PDR5 and YOR1, which are required for normal cycloheximide and oligomycin toleran...

Saccharomyces cerevisiae has long been used as a model organism in the study of the ergosterol pathway and its inhibitors. The Pdr5 protein (Pdr5p), an ATP binding cassette transporter, plays an important role in active efflux of azole antifungals and therefore in azole sensitivity and resistance in S. cerevisiae. We have identified the Fluconazole Dominant Resistance-1 (FDR-1) mutant, which ha...

Citrinin (CIT) and ochratoxin A (OTA) are important mycotoxins, which frequently co-contaminate foodstuff. In order to assess the toxicologic threat posed by the two mycotoxins separately or in combination, their biological effects were studied here using genomic transcription profiling and specific live cell gene expression reporters in yeast cells. Both CIT and OTA cause highly transient tran...

Capsaicin is a pungent element in a variety of red peppers that are widely used as food additives and considered to be an antimicrobial factor. For our tests, we used yeast DNA micro-array methods to understand the mechanisms of inhibitory effects of capsaicin. The capsaicin treatment significantly induced 39 genes from approximately 6,000 genes. These induced genes were classified as multi-dru...

We show that mode of selection, degree of dominance of mutations, and ploidy are determining factors in the evolution of resistance to the antifungal drug fluconazole in yeast. In experiment 1, yeast populations were subjected to a stepwise increase in fluconazole concentration over 400 generations. Under this regimen, two mutations in the same two chromosomal regions rose to high frequency in ...

The lysosome and 26S proteasome represent the two major proteolytic machines in eukaryotic cells (1). While the lysosome deals mainly with nonselective proteolysis, the 26S proteasome handles the majority of regulated proteolysis. The 26S proteasome is a multisubunit protease that degrades the substrate into small peptides in an ATPdependent manner (2,3). The proteasome has three peptidase acti...