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Antimicrobial Agents and Chemotherapy, March 2003, p. 1120-1124, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.1120-1124.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Point Mutation in the 14{alpha}-Sterol Demethylase Gene cyp51A Contributes to Itraconazole Resistance in Aspergillus fumigatus

T. M. Diaz-Guerra, E. Mellado,* M. Cuenca-Estrella, and J. L. Rodriguez-Tudela

Unidad de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain

Received 30 September 2002/ Returned for modification 31 October 2002/ Accepted 5 December 2002

The genes encoding 14{alpha}-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.

* Corresponding author. Mailing address: Unidad de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km2, 28220 Madrid, Spain. Phone: 34-91-5097961. Fax: 34-91-5097966. E-mail: emellado{at}isciii.es.

Antimicrobial Agents and Chemotherapy, March 2003, p. 1120-1124, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.1120-1124.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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