Eukaryotic Cell
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Eukaryotic Cell, January 2008, p. 68-77, Vol. 7, No. 1
1535-9778/08/$08.00+0     doi:10.1128/EC.00256-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Responses of Pathogenic and Nonpathogenic Yeast Species to Steroids Reveal the Functioning and Evolution of Multidrug Resistance Transcriptional Networks{triangledown} ,{dagger}

Dibyendu Banerjee,1,2 Gaelle Lelandais,3,4 Sudhanshu Shukla,1 Gauranga Mukhopadhyay,2 Claude Jacq,3 Frederic Devaux,3*,{ddagger} and Rajendra Prasad1*,{ddagger}

School of Life Sciences, JNU, New Delhi, India,1 Special Centre for Molecular Medicine, JNU, New Delhi, India,2 Laboratoire de Genetique Moleculaire, Ecole Normale Superieure/CNRS UMR 8541,3 Equipe Bioinformatique Génomique et Moléculaire, INSERM U726/Université Paris 7, Paris 75005, France4

Received 16 July 2007/ Accepted 27 October 2007

Steroids are known to induce pleiotropic drug resistance states in hemiascomycetes, with tremendous potential consequences for human fungal infections. Our analysis of gene expression in Saccharomyces cerevisiae and Candida albicans cells subjected 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 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. In particular, 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.

* Corresponding author. Mailing address for Rajendra Prasad: Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Phone: 91-11-26704509. Fax: 91-11-26197338. E-mail: rp47{at}mail.jnu.ac.in. Mailing address for Frederic Devaux: Laboratoire de Genetique Moleculaire, Ecole Normale Superieure/CNRS UMR 8541, Paris 75005, France. Phone: 33 1 44 32 35 72. Fax: 33 1 44 32 39 41. E-mail: devaux{at}biologie.ens.fr

{triangledown} Published ahead of print on 9 November 2007.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

{ddagger} Both authors contributed equally to this work.

Eukaryotic Cell, January 2008, p. 68-77, Vol. 7, No. 1
1535-9778/08/$08.00+0     doi:10.1128/EC.00256-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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