Targeted gene disruption of the 14-alpha sterol demethylase (cyp51A) in Aspergillus fumigatus and its role in azole drug susceptibility.
The role of Aspergillus fumigatus 14alpha-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.
Mellado
E
E
Servicio de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km 2, 28220 Madrid, Spain. emellado@isciii.es
Garcia-Effron
G
G
Buitrago
M J
MJ
Alcazar-Fuoli
L
L
Cuenca-Estrella
M
M
Rodriguez-Tudela
J L
JL
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D001393:Azoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D025141:Drug Resistance, Fungal; D004875:Ergosterol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D004875:Ergosterol