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 loca...

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Detalles Bibliográficos
Autores: Diaz-Guerra, Teresa M., Mellado, Emilia, Cuenca-Estrella, Manuel, Rodriguez-Tudela, Juan Luis
Tipo de recurso: artículo
Fecha de publicación:2003
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/8234
Acceso en línea:http://hdl.handle.net/20.500.12105/8234
Access Level:acceso abierto
Palabra clave:Amino Acid Substitution
Antifungal Agents
Aspergillus fumigatus
Base Sequence
Cytochrome P-450 Enzyme System
Drug Resistance, Fungal
Electroporation
Fungal Proteins
Itraconazole
Microbial Sensitivity Tests
Molecular Sequence Data
Point Mutation
Reverse Transcriptase Polymerase Chain Reaction
Transformation, Genetic
Descripción
Sumario: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.