Targeted Gene Disruption of the 14-α Sterol Demethylase ( cyp51A ) in Aspergillus fumigatus and Its Role in Azole Drug Susceptibility
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چکیده
منابع مشابه
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.
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72 Since the mid-1990s, a steady increase in the occurrence of itraconazole resistant Aspergillus 73 fumigatus isolates has been observed in clinical contexts leading to therapeutic failure in the 74 treatment of aspergillosis. This increase has been predominantly linked to a single allele of 75 the cyp51A gene, termed ‘TR/L98H’ which is thought to have arisen through the use of 76 agricultural...
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The genes encoding 14alpha-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-...
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Aspergillus fumigatus sterol 14α-demethylase isoenzymes CYP51A and CYP51B were heterologously expressed in a Saccharomyces cerevisiae mutant (YUG37-erg11), wherein native ERG11/CYP51 expression is controlled using a doxycycline-regulatable promoter. When cultured in the presence of doxycycline, recombinant YUG37-pcyp51A and YUG37-pcyp51B yeasts were able to synthesize ergosterol and grow; a con...
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ژورنال
عنوان ژورنال: Antimicrobial Agents and Chemotherapy
سال: 2005
ISSN: 0066-4804,1098-6596
DOI: 10.1128/aac.49.6.2536-2538.2005