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

ABSTRACTTwo erg3genes encoding C-5 sterol desaturase enzymes (Erg3A and Erg3B) in Aspergillus fumigatuswere characterized with respect to their nucleotide sequences and null mutant phenotypes. Targeted disruption of the erg3Aand erg3Bgenes and a double gene knockout, erg3A−erg3B−, showed that they are not essential for A. fumigatusviability. Mutant phenotypes clearly showed that Erg3B is a C-5 sterol desaturase, but no apparent role for Erg3A in A. fumigatusergosterol biosynthesis was found. Susceptibility to amphotericin B, itraconazole, fluconazole, voriconazole, and ketoconazole was not altered in isolates in which erg3Aand erg3Bwere knocked out alone and in combination.