Responses of pathogenic and nonpathogenic yeast species to steroids reveal the functioning and evolution of multidrug resistance transcriptional networks.
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.
Banerjee
Dibyendu
D
Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Lelandais
Gaelle
G
Shukla
Sudhanshu
S
Mukhopadhyay
Gauranga
G
Jacq
Claude
C
Devaux
Frederic
F
Prasad
Rajendra
R
D005075:Biological Evolution; D015152:Blotting, Northern; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D004875:Ergosterol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C085480:PDR1 protein, S cerevisiae; C089261:PDR3 protein, S cerevisiae; D011372:Progestins; D029701:Saccharomyces cerevisiae Proteins; D013256:Steroids; D015534:Trans-Activators; D014157:Transcription Factors; D011374:Progesterone; D004875:Ergosterol