Overexpression of the MDR1 gene is sufficient to confer increased resistance to toxic compounds in Candida albicans

Details

Serval ID
serval:BIB_4A06EFAC4C56
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Overexpression of the MDR1 gene is sufficient to confer increased resistance to toxic compounds in Candida albicans
Journal
Antimicrobial Agents and Chemotherapy
Author(s)
Hiller  D., Sanglard  D., Morschhauser  J.
ISSN
0066-4804 (Print)
Publication state
Published
Issued date
04/2006
Volume
50
Number
4
Pages
1365-71
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Abstract
Overexpression of MDR1, which encodes a membrane transport protein of the major facilitator superfamily, is one mechanism by which the human fungal pathogen Candida albicans can develop increased resistance to the antifungal drug fluconazole and other toxic compounds. In clinical C. albicans isolates, constitutive MDR1 overexpression is accompanied by the upregulation of other genes, but it is not known if these additional alterations are required for Mdr1p function and drug resistance. To investigate whether MDR1 overexpression is sufficient to confer a drug-resistant phenotype in C. albicans, we expressed the MDR1 gene from the strong ADH1 promoter in C. albicans laboratory strains that did not express the endogenous MDR1 gene as well as in a fluconazole-resistant clinical C. albicans isolate in which the endogenous MDR1 alleles had been deleted and in a matched fluconazole-susceptible isolate from the same patient. Forced MDR1 overexpression resulted in increased resistance to the putative Mdr1p substrates cerulenin and brefeldin A, and this resistance did not depend on the additional alterations which occurred during drug resistance development in the clinical isolates. In contrast, artificial expression of the MDR1 gene from the ADH1 promoter did not enhance or only slightly enhanced fluconazole resistance, presumably because Mdr1p expression levels in the transformants were considerably lower than those observed in the fluconazole-resistant clinical isolate. These results demonstrate that MDR1 overexpression in C. albicans is sufficient to confer resistance to some toxic compounds that are substrates of this efflux pump but that the degree of resistance depends on the Mdr1p expression level.
Keywords
Candida albicans/*drug effects/genetics Drug Resistance, Fungal Fluconazole/pharmacology *Genes, MDR Humans Promoter Regions (Genetics)
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:40
Last modification date
20/08/2019 13:57
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