A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus.
The genes encoding 14alpha-sterol demethylases (cyp51A and cyp51B) were analyzed in 12 itraconazole (ITC)-resistant and three ITC-susceptible clinical isolates of Aspergillus fumigatus. Six ITC-resistant strains exhibited a substitution of another amino acid for glycine at position 54, which is located at a very conserved region of the Cyp51A protein. The cyp51A gene from the A. fumigatus wild-type strain (CM-237) was replaced with the mutated cyp51A gene copy of an ITC-resistant strain (AF-72). Two transformants exhibited resistance to ITC, both of which had incorporated the mutated copy of the cyp51A gene.
Diaz-Guerra
T M
TM
Unidad de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Mellado
E
E
Cuenca-Estrella
M
M
Rodriguez-Tudela
J L
JL
D019943:Amino Acid Substitution; D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics*; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D025141:Drug Resistance, Fungal; D018274:Electroporation; D005656:Fungal Proteins / Q000235:genetics*; D017964:Itraconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014170:Transformation, Genetic
D000935:Antifungal Agents; D005656:Fungal Proteins; D017964:Itraconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; C465527:cytochrome P-450 CYP51B, Aspergillus