Aspergillus fumigatus C-5 Sterol Desaturases Erg3A and Erg3B: Role in Sterol Biosynthesis and Antifungal Drug Susceptibility

Author:

Alcazar-Fuoli Laura1,Mellado Emilia1,Garcia-Effron Guillermo1,Buitrago Maria J.1,Lopez Jordi F.2,Grimalt Joan O.2,Cuenca-Estrella J. Manuel1,Rodriguez-Tudela Juan L.1

Affiliation:

1. Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain

2. Department of Environmental Chemistry, I.C.E.R.-C.S.I.C., Jordi Girona, 18, 08034 Barcelona, Spain

Abstract

ABSTRACT Two erg3 genes encoding C-5 sterol desaturase enzymes (Erg3A and Erg3B) in Aspergillus fumigatus were characterized with respect to their nucleotide sequences and null mutant phenotypes. Targeted disruption of the erg3A and erg3B genes and a double gene knockout, erg3A erg3B , showed that they are not essential for A. fumigatus viability. Mutant phenotypes clearly showed that Erg3B is a C-5 sterol desaturase, but no apparent role for Erg3A in A. fumigatus ergosterol biosynthesis was found. Susceptibility to amphotericin B, itraconazole, fluconazole, voriconazole, and ketoconazole was not altered in isolates in which erg3A and erg3B were knocked out alone and in combination.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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