A Point Mutation in the 14α-Sterol Demethylase Gene cyp51A Contributes to Itraconazole Resistance in Aspergillus fumigatus
Author(s) -
Teresa M. Dı́az-Guerra,
Emilia Mellado,
M. Cuenca-Estrella,
J. L. Rodríguez-Tudela
Publication year - 2004
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.48.3.1071.2004
Subject(s) - aspergillus fumigatus , itraconazole , point mutation , demethylase , sterol , microbiology and biotechnology , gene , biology , fungi imperfecti , aspergillus , mutation , genetics , antifungal , biochemistry , cholesterol , epigenetics
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.
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