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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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first_indexed 2015-10-07T18:49:18Z
last_indexed 2021-10-30T02:37:28Z
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spelling 2021-10-29T10:06:45.8509928 v2 23614 2015-10-07 In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus e563ed4e1c7db8d1e131fb78a5f8d0d5 Josie Parker Josie Parker true false 9a4e4dfa37f4318c6fa67933d4fc9a17 0000-0002-6045-4835 Claire Price Claire Price true false b17cebaf09b4d737b9378a3581e3de93 0000-0001-7991-5040 Steven Kelly Steven Kelly true false 5ccf81e5d5beedf32ef8d7c3d7ac6c8c Diane Kelly Diane Kelly true false 2015-10-07 FGMHL 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. Journal Article Antimicrobial Agents and Chemotherapy 59 12 7771 7778 American Society for Microbiology 0066-4804 1098-6596 antifungal; Aspergillus fumigatus; CYP 51; CPR; POINT MUTATIONS 1 12 2015 2015-12-01 10.1128/aac.01806-15 http://dx.doi.org/10.1128/aac.01806-15 COLLEGE NANME Medicine, Health and Life Science - Faculty COLLEGE CODE FGMHL Swansea University 2021-10-29T10:06:45.8509928 2015-10-07T12:32:07.0954056 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Andrew G. S. Warrilow 1 Josie Parker 2 Claire Price 0000-0002-6045-4835 3 W. David Nes 4 Steven Kelly 0000-0001-7991-5040 5 Diane Kelly 6
title In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus
spellingShingle In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus
Josie Parker
Claire Price
Steven Kelly
Diane Kelly
title_short In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus
title_full In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus
title_fullStr In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus
title_full_unstemmed In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus
title_sort In Vitro Biochemical Study of CYP51-Mediated Azole Resistance in Aspergillus fumigatus
author_id_str_mv e563ed4e1c7db8d1e131fb78a5f8d0d5
9a4e4dfa37f4318c6fa67933d4fc9a17
b17cebaf09b4d737b9378a3581e3de93
5ccf81e5d5beedf32ef8d7c3d7ac6c8c
author_id_fullname_str_mv e563ed4e1c7db8d1e131fb78a5f8d0d5_***_Josie Parker
9a4e4dfa37f4318c6fa67933d4fc9a17_***_Claire Price
b17cebaf09b4d737b9378a3581e3de93_***_Steven Kelly
5ccf81e5d5beedf32ef8d7c3d7ac6c8c_***_Diane Kelly
author Josie Parker
Claire Price
Steven Kelly
Diane Kelly
author2 Andrew G. S. Warrilow
Josie Parker
Claire Price
W. David Nes
Steven Kelly
Diane Kelly
format Journal article
container_title Antimicrobial Agents and Chemotherapy
container_volume 59
container_issue 12
container_start_page 7771
publishDate 2015
institution Swansea University
issn 0066-4804
1098-6596
doi_str_mv 10.1128/aac.01806-15
publisher American Society for Microbiology
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url http://dx.doi.org/10.1128/aac.01806-15
document_store_str 0
active_str 0
description 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.
published_date 2015-12-01T03:27:53Z
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score 11.013194

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