Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate

Details

Serval ID
serval:BIB_B85B025DEBD3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate
Journal
Fungal Genetics and Biology
Author(s)
Slaven  J. W., Anderson  M. J., Sanglard  D., Dixon  G. K., Bille  J., Roberts  I. S., Denning  D. W.
ISSN
1087-1845 (Print)
Publication state
Published
Issued date
08/2002
Volume
36
Number
3
Pages
199-206
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
Abstract
Aspergillus fumigatus is the most frequent causative agent of invasive aspergillosis. Itraconazole became available in 1990 to treat invasive aspergillosis, but instances of resistance have now been described. Drug efflux was a proposed mechanism in one itraconazole resistant clinical isolate (AF72) which accumulates low levels of the drug. Drug efflux in fungi can be mediated by ATP-binding cassette transporter (ABCT) genes, such as CDR1 in Candida albicans. Using a probe derived from CDR1, a gene, atrF, was cloned from A. fumigatus. The atrF gene product (AtrF) is 1547 amino acids long and has characteristic multidrug resistance motifs. Dot blot analysis revealed that AF72 has approximately 5-fold higher levels of atrF mRNA than susceptible isolates AF10 and H06-03 in cultures with sub-minimum inhibitory concentration (sub-MIC) levels of itraconazole. atrF is the first ABCT gene cloned from A. fumigatus, whose overexpression is correlated with itraconazole resistance.
Keywords
ATP-Binding Cassette Transporters/chemistry/genetics/*metabolism Amino Acid Sequence Antifungal Agents/pharmacology Aspergillus fumigatus/drug effects/*genetics/metabolism Base Sequence Cloning, Molecular Drug Resistance, Microbial/*physiology Gene Expression Regulation, Fungal/drug effects Immunoblotting Itraconazole/*pharmacology Microbial Sensitivity Tests Molecular Sequence Data
Pubmed
Web of science
Create date
25/01/2008 14:40
Last modification date
20/08/2019 15:26
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