Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/8260
Substitutions at methionine 220 in the 14alpha-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs
Mellado, Emilia ISCIII | Garcia-Effron, Guillermo ISCIII | Alcazar-Fuoli, Laura ISCIII | Cuenca-Estrella, Manuel ISCIII | Rodriguez-Tudela, Juan Luis ISCIII
Antimicrob Agents Chemother. 2004 Jul;48(7):2747-50.
Five clinical isolates of Aspergillus fumigatus that exhibited similar patterns of reduced susceptibility to itraconazole and other triazole drugs were analyzed. Sequence analysis of genes (cyp51A and cyp51B) encoding the 14alpha-sterol demethylases revealed that all five strains harbored mutations in cyp51A resulting in the replacement of methionine at residue 220 by valine, lysine, or threonine. When the mutated cyp51A genes were introduced into an A. fumigatus wild-type strain, the transformants exhibited reduced susceptibility to all triazole agents, confirming that the mutations were responsible for the resistance phenotype.
Alleles | Amino Acid Sequence | Amino Acid Substitution | Antifungal Agents | Aspergillus fumigatus | Azoles | Cytochrome P-450 Enzyme System | Drug Resistance, Fungal | Fungal Proteins | Methionine | Microbial Sensitivity Tests | Molecular Sequence Data | Mutation | Reverse Transcriptase Polymerase Chain Reaction