Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene
Details
Serval ID
serval:BIB_F7842E8C6D5A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene
Journal
Microbiology
ISSN
1350-0872 (Print)
Publication state
Published
Issued date
02/1997
Volume
143 ( Pt 2)
Pages
405-16
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Abstract
Resistance to azole antifungal agents in Candida albicans can be mediated by multidrug efflux transporters. In a previous study, we identified at least two such transporters, Cdr1p and Benp, which belong to the class of ATP-binding cassette (ABC) transporters and of major facilitators, respectively. To isolate additional factors potentially responsible for resistance to azole antifungal agents in C. albicans, the hypersusceptibility of a Saccharomyces cerevisiae multidrug transporter mutant, delta pdr5, to these agents was complemented with a C. albicans genomic library. Several new genes were isolated, one of which was a new ABC transporter gene called CDR2 (Candida drug resistance). The protein Cdr2p encoded by this gene exhibited 84% identity with Cdr1p and could confer resistance to azole antifungal agents, to other antifungals (terbinafine, amorolfine) and to a variety of metabolic inhibitors. The disruption of CDR2 in the C. albicans strain CAF4-2 did not render cells more susceptible to these substances. When the disruption of CDR2 was performed in the background of a mutant in which CDR1 was deleted, the resulting double delta cdr1 delta cdr2 mutant was more susceptible to these agents than the single delta cdr1 mutant. The absence of hypersusceptibility of the single delta cdr2 mutant could be explained by the absence of CDR2 mRNA in azole-susceptible C. albicans strains. CDR2 was overexpressed, however, in clinical C. albicans isolates resistant to azole antifungal agents as described previously for CDR1, but to levels exceeding or equal to those reached by CDR1. Interestingly, CDR2 expression was restored in delta cdr1 mutants reverting spontaneously to wild-type levels of susceptibility to azole antifungal agents. These data demonstrate that CDR2 plays an important role in mediating the resistance of C. albicans to azole antifungal agents.
Keywords
ATP-Binding Cassette Transporters/*genetics/metabolism
Amino Acid Sequence
Antifungal Agents/*pharmacology
Base Sequence
Biological Transport
Candida albicans/*genetics
Candidiasis, Oral/microbiology
Cloning, Molecular
Drug Resistance, Microbial/*genetics
Fungal Proteins/genetics
*Genes, Fungal
Humans
*Membrane Transport Proteins
Microbial Sensitivity Tests
Molecular Sequence Data
Mutagenesis
Restriction Mapping
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 16:46
Last modification date
20/08/2019 16:23