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In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus

Andrew G. S. Warrilow, Josie Parker, Claire Price Orcid Logo, W. David Nes, Steven Kelly Orcid Logo, Diane Kelly

Antimicrobial Agents and Chemotherapy, Volume: 59, Issue: 12, Pages: 7771 - 7778

Swansea University Authors: Josie Parker, Claire Price Orcid Logo, Steven Kelly Orcid Logo, Diane Kelly

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DOI (Published version): 10.1128/aac.01806-15

Abstract

New classes of azole-based drugs are required to combat the increasing resistance to existing triazole therapeutics. In this study, a CYP51 reconstitution assay is described consisting of eburicol, purified recombinant Aspergillus fumigatus CPR1 (AfCPR1), and Escherichia coli membrane suspensions co...

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Published in: Antimicrobial Agents and Chemotherapy
ISSN: 0066-4804 1098-6596
Published: American Society for Microbiology 2015
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URI: https://cronfa.swan.ac.uk/Record/cronfa23614
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Abstract: New classes of azole-based drugs are required to combat the increasing resistance to existing triazole therapeutics. In this study, a CYP51 reconstitution assay is described consisting of eburicol, purified recombinant Aspergillus fumigatus CPR1 (AfCPR1), and Escherichia coli membrane suspensions containing recombinant A. fumigatus CYP51 proteins, allowing in vitro screening of azole antifungals. Our AfCPR1/Af51 assay system demonstrated the biochemical basis for the increased azole resistance of A. fumigatus strains harboring G54W, L98H, and M220K Af51A point mutations.
Keywords: antifungal; Aspergillus fumigatus; CYP 51; CPR; POINT MUTATIONS
College: Faculty of Medicine, Health and Life Sciences
Issue: 12
Start Page: 7771
End Page: 7778