Journal article
Regulation of the CgPdr1 Transcription Factor from the Pathogen Candida glabrata
Eukaryotic cell, Vol.10(2), pp.187-197
02/2011
DOI: 10.1128/EC.00277-10
PMCID: PMC3067410
PMID: 21131438
Abstract
ABSTRACT
Candida glabrata
is an opportunistic human pathogen that is increasingly associated with candidemia, owing in part to the intrinsic and acquired high tolerance the organism exhibits for the important clinical antifungal drug fluconazole. This elevated fluconazole resistance often develops through gain-of-function mutations in the zinc cluster-containing transcriptional regulator
C. glabrata
Pdr1 (CgPdr1). CgPdr1 induces the expression of an ATP-binding cassette (ABC) transporter-encoding gene, Cg
CDR1
.
Saccharomyces cerevisiae
has two CgPdr1 homologues called ScPdr1 and ScPdr3. These factors control the expression of an ABC transporter-encoding gene called Sc
PDR5
, which encodes a homologue of Cg
CDR1
. Loss of the mitochondrial genome (ρ
0
cell) or overexpression of the mitochondrial enzyme ScPsd1 induces Sc
PDR5
expression in a strictly ScPdr3-dependent fashion. ScPdr3 requires the presence of a transcriptional Mediator subunit called Gal11 (Med15) to fully induce Sc
PDR5
transcription in response to ρ
0
signaling. ScPdr1 does not respond to either ρ
0
signals or ScPsd1 overproduction. In this study, we employed transcriptional fusions between CgPdr1 target promoters, like Cg
CDR1
, to demonstrate that CgPdr1 stimulates gene expression via binding to elements called pleiotropic drug response elements (PDREs). Deletion mapping and electrophoretic mobility shift assays demonstrated that a single PDRE in the Cg
CDR1
promoter was capable of supporting ρ
0
-induced gene expression. Removal of one of the two ScGal11 homologues from
C. glabrata
caused a major defect in drug-induced expression of Cg
CDR1
but had a quantitatively minor effect on ρ
0
-stimulated transcription. These data demonstrate that CgPdr1 appears to combine features of ScPdr1 and ScPdr3 to produce a transcription factor with chimeric regulatory properties.
Details
- Title: Subtitle
- Regulation of the CgPdr1 Transcription Factor from the Pathogen Candida glabrata
- Creators
- Sanjoy Paul - University of IowaJennifer A. Schmidt - University of IowaW. Scott Moye-Rowley - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Eukaryotic cell, Vol.10(2), pp.187-197
- DOI
- 10.1128/EC.00277-10
- PMID
- 21131438
- PMCID
- PMC3067410
- NLM abbreviation
- Eukaryot Cell
- ISSN
- 1535-9778
- eISSN
- 1535-9786
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 02/2011
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297598702771
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