A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance

Détails

ID Serval
serval:BIB_64053B5984C2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance
Périodique
Molecular Microbiology
Auteur(s)
de Micheli  M., Bille  J., Schueller  C., Sanglard  D.
ISSN
0950-382X (Print)
Statut éditorial
Publié
Date de publication
03/2002
Volume
43
Numéro
5
Pages
1197-214
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Résumé
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.
Mots-clé
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
Création de la notice
25/01/2008 15:40
Dernière modification de la notice
20/08/2019 15:20
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