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Antimicrobial Agents and Chemotherapy, June 2005, p. 2536-2538, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2536-2538.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Targeted Gene Disruption of the 14-{alpha} Sterol Demethylase (cyp51A) in Aspergillus fumigatus and Its Role in Azole Drug Susceptibility

E. Mellado,* G. Garcia-Effron, M. J. Buitrago, L. Alcazar-Fuoli, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela

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

Received 1 September 2004/ Returned for modification 8 October 2004/ Accepted 31 January 2005

The role of Aspergillus fumigatus 14{alpha}-sterol demethylase (Cyp51A) in azole drug susceptibility was assessed. Targeted disruption of cyp51A in azole-susceptible and -resistant strains decreased MICs from 2- to 40-fold. The cyp51A mutants were morphologically indistinguishable from the wild-type strain, retaining the ability to cause pulmonary disease in neutropenic mice.

* Corresponding author. Mailing address: Servicio de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km 2, 28220 Madrid, Spain. Phone: 34-91-5097961. Fax: 34-91-5097966. E-mail: emellado{at}isciii.es.

Antimicrobial Agents and Chemotherapy, June 2005, p. 2536-2538, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2536-2538.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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