A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance
Details
Serval ID
serval:BIB_64053B5984C2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance
Journal
Molecular Microbiology
ISSN
0950-382X (Print)
Publication state
Published
Issued date
03/2002
Volume
43
Number
5
Pages
1197-214
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Research Support, Non-U.S. Gov't --- Old month value: Mar
Abstract
Upregulation of the ATP-binding cassette (ABC) transporter genes CDR1 and CDR2 (Candida drug resistance 1 and 2) is a common mechanism observed in Candida albicans clinical isolates developing resistance to the class of azole antifungals. In this work, the regulatory elements of both genes were delimited using a reporter system in an azole-susceptible strain exposed to oestradiol, which allows transient induction of these genes. We found two regulatory elements in the CDR1 promoter: one responsible for basal expression (basal expression element; BEE) and the other required for oestradiol responsiveness (drug-responsive element I; DREI). In the CDR2 promoter, a single regulatory element responsible for oestradiol responsiveness (DREII) was detected. Both DREs shared a consensus of 21 bp with the sequence 5'-CGGA(A/T)ATCGGATATTTTTTTT-3' having no equivalent to known eukaryotic regulatory sequence. Consistent with this finding, two other C. albicans genes identified by a search for the presence of DRE in the C. albicans genome sequence database were responsive to oestradiol. Finally, the regulatory elements found in CDR1 and CDR2 were also functional in an azole-resistant strain with constitutive high expression of both transporters. These results suggest that, although CDR1 and CDR2 upregulation can be obtained by transient drug-induced and constitutive upregulation, these two processes converge to the same regulatory elements and probably mobilize the same trans-acting factors.
Keywords
ATP-Binding Cassette Transporters/genetics/*metabolism
Antifungal Agents/pharmacology
Base Sequence
Candida albicans/*drug effects
Drug Resistance, Fungal
Estradiol/pharmacology
Fungal Proteins/genetics/*metabolism
*Gene Expression Regulation, Fungal
Humans
Membrane Transport Proteins/genetics/*metabolism
Molecular Sequence Data
Promoter Regions (Genetics)/genetics
Sequence Analysis, DNA
Pubmed
Web of science
Create date
25/01/2008 15:40
Last modification date
20/08/2019 15:20