Differences in Interactions between Azole Drugs Related to Modifications in the 14-α Sterol Demethylase Gene ( cyp51A ) of Aspergillus fumigatus
نویسندگان
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.
متن کاملcyp51A-based mechanisms of Aspergillus fumigatus azole
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...
متن کاملA point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus.
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-...
متن کاملComplementation of a Saccharomyces cerevisiae ERG11/CYP51 (sterol 14α-demethylase) doxycycline-regulated mutant and screening of the azole sensitivity of Aspergillus fumigatus isoenzymes CYP51A and CYP51B.
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...
متن کاملSensitisation of an Azole-Resistant Aspergillus fumigatus Strain containing the Cyp51A-Related Mutation by Deleting the SrbA Gene
Azoles are widely used for controlling fungal growth in both agricultural and medical settings. The target protein of azoles is CYP51, a lanosterol 14-α-demethylase involved in the biosynthesis of ergosterol. Recently, a novel azole resistance mechanism has arisen in pathogenic fungal species Aspergillus fumigatus. Resistant strains contain a 34-bp or 46-bp tandem repeat (TR) in the promoter of...
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ژورنال
عنوان ژورنال: Antimicrobial Agents and Chemotherapy
سال: 2005
ISSN: 0066-4804,1098-6596
DOI: 10.1128/aac.49.5.2119-2121.2005