An Improved Model of the Aspergillus fumigatus CYP51A Protein

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cyp51A-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...

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Azole resistance profile of amino acid changes in Aspergillus fumigatus CYP51A based on protein homology modeling.

Molecular studies have shown that the majority of azole resistance in Aspergillus fumigatus is associated with amino acid substitutions in the cyp51A gene. To obtain insight into azole resistance mutations, the cyp51A gene of 130 resistant and 76 susceptible A. fumigatus isolates was sequenced. Out of 130 azole-resistant isolates, 105 contained a tandem repeat of 34 bp in the promoter region an...

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Efficacy of posaconazole against three clinical Aspergillus fumigatus isolates with mutations in the cyp51A gene.

The in vivo efficacy of posaconazole against 4 clinical Aspergillus fumigatus isolates with posaconazole MICs ranging from 0.03 to 16 mg/liter, as determined by CLSI method M38A, was assessed in a nonneutropenic murine model of disseminated aspergillosis. The underlying resistance mechanisms of the isolates included substitutions in the cyp51A gene at codon 220 (M220I), codon 54 (G54W), and cod...

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Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae.

Azole-resistant strains of Aspergillus fumigatus have been detected and the underlying molecular mechanisms of resistance characterized. Point mutations in the cyp51A gene have been proved to be related to azole resistance in A. fumigatus clinical strains and with different resistance profiles depending on the amino acid change (G54E, G54V, G54R, G54W, M220V, M220K, M220T, M220I). The aim of th...

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The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus.

OBJECTIVES Recent increases in triazole resistance in Aspergillus fumigatus have been attributed primarily to target site (cyp51A) mutations. A recent survey of resistant isolates in Manchester showed that >50% of resistant isolates had no mutation in cyp51A or its promoter. We investigated the mechanisms of resistance in clinical azole-resistant isolates without cyp51A mutations. METHODS Twe...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2011

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.01651-10