Unveiling the transcriptional control of pleiotropic drug resistance in Saccharomyces cerevisiae: Contributions of André Goffeau and his group.

Abstract

Studies in the yeast Saccharomyces cerevisiae have provided much of the basic detail underlying the organization and regulation of multiple or pleiotropic drug resistance gene network in eukaryotic microbes. As with many aspects of yeast biology, the initial observations that drove the eventual molecular characterization of multidrug resistance gene were provided by genetics. This review focuses on contributions from the laboratory of Dr. André Goffeau that uncovered key aspects of the transcriptional regulation of these multidrug resistance genes. André's group made many seminal discoveries that helped lead to the current picture we have of how eukaryotic microbes respond to and deal with a variety of antifungal agents. The importance of the transcriptional contribution to antifungal drugs is illustrated by the large number of drug resistant mutants found in several yeast species that lead to increased activity of transcriptional regulators. The characterization of the Saccharomyces cerevisiae PDR1 gene by the Goffeau group provided the first molecular basis explaining the link between this hyperactive transcription factor and drug resistance.