The steroid responses of pathogenic and non-pathogenic yeast species enlighten the functioning and evolution of multidrug resistance transcriptional networks

School of Life Sciences, JNU, New Delhi, India; Special Centre for Molecular Medicine, JNU, New Delhi, India; Laboratoire de genetique moleculaire, Ecole normale superieure/CNRS UMR 8541; Equipe Bioinformatique Génomique et Moléculaire INSERM U726/Université Paris 7, Paris 75005, France

^* To whom correspondence should be addressed. Email: devaux{at}biologie.ens.fr. rp47{at}mail.jnu.ac.in.

	Abstract

Steroids are known to induce pleiotropic drug resistance states in hemiascomycetes, with tremendous potential consequences on human fungal infections. Our analysis of gene expression in Saccharomyces cerevisiae and Candida albicans cells submitted to three different concentrations of progesterone revealed that their Pleiotropic Drug Resistance (PDR) networks were strikingly sensitive to steroids. In S. cerevisiae, 20 of the Pdr1p/Pdr3p target genes, including PDR3 itself, were rapidly induced by progesterone, which mimics the effects of PDR1 gain of function alleles. This unique property allowed us to decipher the respective roles of Pdr1p and Pdr3p in the PDR induction and to define functional modules among their target genes. Although the expression profiles of the major PDR transporters encoding genes ScPDR5 and CaCDR1 were similar, the S. cerevisiae global PDR response to progesterone was only partly conserved in C. albicans. Especially, the role of Tac1p, the main C. albicans PDR regulator, in the progesterone response was apparently restricted to five genes. These results suggest that the C. albicans and S. cerevisiae PDR networks, although sharing a conserved core regarding the regulation of membrane properties, have different structures and properties. Additionally, our data indicate that other as yet undiscovered regulators may second Tac1p in the C. albicans drug response.