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Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa

Andrew Warrilow, Claire Price Orcid Logo, Josie Parker, Nicola J. Rolley, Christopher J. Smyrniotis, David D. Hughes, Vera Thoss, W. David Nes, Diane Kelly, Theodore R. Holman, Steven Kelly Orcid Logo

Scientific Reports, Volume: 6, Issue: 1

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

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DOI (Published version): 10.1038/srep27690

Abstract

Malassezia species are known to play a role in several human skin diseases including dandruff, seborrheic dermatitis, pityriasis versicolor and malassezia folliculitis and may also exacerbate atopic dermatitis and psoriasis even though they are members of the normal skin microbial flora, being prese...

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Published in: Scientific Reports
ISSN: 2045-2322
Published: 2016
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URI: https://cronfa.swan.ac.uk/Record/cronfa34335
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spelling 2017-07-06T16:59:35.1505901 v2 34335 2017-06-14 Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa f066e233e8d0136c9f547b86fa43747f Andrew Warrilow Andrew Warrilow true false 9a4e4dfa37f4318c6fa67933d4fc9a17 0000-0002-6045-4835 Claire Price Claire Price true false e563ed4e1c7db8d1e131fb78a5f8d0d5 Josie Parker Josie Parker true false 5ccf81e5d5beedf32ef8d7c3d7ac6c8c Diane Kelly Diane Kelly true false b17cebaf09b4d737b9378a3581e3de93 0000-0001-7991-5040 Steven Kelly Steven Kelly true false 2017-06-14 FGMHL Malassezia species are known to play a role in several human skin diseases including dandruff, seborrheic dermatitis, pityriasis versicolor and malassezia folliculitis and may also exacerbate atopic dermatitis and psoriasis even though they are members of the normal skin microbial flora, being present on the skin of 75 to 98% of healthy individuals. There are presently fourteen recognized species of Malassezia, eight of which are associated with humans. Malassezia are unique amongst fungi in requiring exogenous lipids for growth. We have investigated Malassezia globosa cytochromes P450 CYP51 and CYP5218 as sterol 14α-demethylase (the target of azole antifungals) and a putative fatty acid metabolism protein (and a potential azole drug target), respectively. MIC100 studies showed itraconazole should be considered as an alternative to ketoconazole given the potency and safety profiles and the CYP51 assay system can be used in structure-activity studies in drug development. Journal Article Scientific Reports 6 1 2045-2322 31 12 2016 2016-12-31 10.1038/srep27690 COLLEGE NANME Medicine, Health and Life Science - Faculty COLLEGE CODE FGMHL Swansea University 2017-07-06T16:59:35.1505901 2017-06-14T09:28:13.7035457 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Andrew Warrilow 1 Claire Price 0000-0002-6045-4835 2 Josie Parker 3 Nicola J. Rolley 4 Christopher J. Smyrniotis 5 David D. Hughes 6 Vera Thoss 7 W. David Nes 8 Diane Kelly 9 Theodore R. Holman 10 Steven Kelly 0000-0001-7991-5040 11
title Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
spellingShingle Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
Andrew Warrilow
Claire Price
Josie Parker
Diane Kelly
Steven Kelly
title_short Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
title_full Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
title_fullStr Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
title_full_unstemmed Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
title_sort Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa
author_id_str_mv f066e233e8d0136c9f547b86fa43747f
9a4e4dfa37f4318c6fa67933d4fc9a17
e563ed4e1c7db8d1e131fb78a5f8d0d5
5ccf81e5d5beedf32ef8d7c3d7ac6c8c
b17cebaf09b4d737b9378a3581e3de93
author_id_fullname_str_mv f066e233e8d0136c9f547b86fa43747f_***_Andrew Warrilow
9a4e4dfa37f4318c6fa67933d4fc9a17_***_Claire Price
e563ed4e1c7db8d1e131fb78a5f8d0d5_***_Josie Parker
5ccf81e5d5beedf32ef8d7c3d7ac6c8c_***_Diane Kelly
b17cebaf09b4d737b9378a3581e3de93_***_Steven Kelly
author Andrew Warrilow
Claire Price
Josie Parker
Diane Kelly
Steven Kelly
author2 Andrew Warrilow
Claire Price
Josie Parker
Nicola J. Rolley
Christopher J. Smyrniotis
David D. Hughes
Vera Thoss
W. David Nes
Diane Kelly
Theodore R. Holman
Steven Kelly
format Journal article
container_title Scientific Reports
container_volume 6
container_issue 1
publishDate 2016
institution Swansea University
issn 2045-2322
doi_str_mv 10.1038/srep27690
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
document_store_str 0
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description Malassezia species are known to play a role in several human skin diseases including dandruff, seborrheic dermatitis, pityriasis versicolor and malassezia folliculitis and may also exacerbate atopic dermatitis and psoriasis even though they are members of the normal skin microbial flora, being present on the skin of 75 to 98% of healthy individuals. There are presently fourteen recognized species of Malassezia, eight of which are associated with humans. Malassezia are unique amongst fungi in requiring exogenous lipids for growth. We have investigated Malassezia globosa cytochromes P450 CYP51 and CYP5218 as sterol 14α-demethylase (the target of azole antifungals) and a putative fatty acid metabolism protein (and a potential azole drug target), respectively. MIC100 studies showed itraconazole should be considered as an alternative to ketoconazole given the potency and safety profiles and the CYP51 assay system can be used in structure-activity studies in drug development.
published_date 2016-12-31T03:42:35Z
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