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Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance

James O’Connor-Moneley, Jessica Fletcher Orcid Logo, Cody Bean, Josie Parker, Steven Kelly, Gary P. Moran, Derek J. Sullivan Orcid Logo

PLOS ONE, Volume: 19, Issue: 8, Start page: e0308665

Swansea University Author: Steven Kelly

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DOI (Published version): 10.1371/journal.pone.0308665

Abstract

Development of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Media...

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Published in: PLOS ONE
ISSN: 1932-6203
Published: Public Library of Science (PLoS) 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa67874
first_indexed 2024-10-01T14:03:45Z
last_indexed 2024-11-25T14:21:00Z
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spelling 2024-11-04T13:53:30.0476294 v2 67874 2024-10-01 Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance b17cebaf09b4d737b9378a3581e3de93 Steven Kelly Steven Kelly true false 2024-10-01 Development of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Mediator complex which is involved in the global control of transcription. This study investigates the acquisition of fluconazole tolerance in a mutant in which the entire TLO gene family has been deleted. This phenotype was reversed to varying degrees upon reintroduction of representative members of the alpha- and beta-TLO clades (i.e. TLO1 and TLO2), but not by TLO11, a gamma-clade representative. Comparative RNA sequencing analysis revealed changes in the expression of genes involved in a range of cellular functions, including ergosterol biosynthesis, mitochondrial function, and redox homeostasis. This was supported by the results of mass spectrometry analysis, which revealed alterations in sterol composition of the mutant cell membrane. Our data suggest that members of the C. albicans TLO gene family are involved in the control of ergosterol biosynthesis and mitochondrial function and may play a role in the responses of C. albicans to azole antifungal agents. Journal Article PLOS ONE 19 8 e0308665 Public Library of Science (PLoS) 1932-6203 9 8 2024 2024-08-09 10.1371/journal.pone.0308665 COLLEGE NANME COLLEGE CODE Swansea University Another institution paid the OA fee DJS - and GPM - Science Foundation Ireland 19/FFP/6422 www.sfi.ie 2024-11-04T13:53:30.0476294 2024-10-01T14:53:16.1064558 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science James O’Connor-Moneley 1 Jessica Fletcher 0000-0002-8737-1538 2 Cody Bean 3 Josie Parker 4 Steven Kelly 5 Gary P. Moran 6 Derek J. Sullivan 0000-0003-0195-9697 7 67874__32834__a51d956261c1460cb97b5635cad9288d.pdf 67874.VoR.pdf 2024-11-04T13:51:57.7026630 Output 2949541 application/pdf Version of Record true © 2024 O’Connor-Moneley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. true eng http://creativecommons.org/licenses/by/4.0/
title Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance
spellingShingle Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance
Steven Kelly
title_short Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance
title_full Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance
title_fullStr Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance
title_full_unstemmed Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance
title_sort Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance
author_id_str_mv b17cebaf09b4d737b9378a3581e3de93
author_id_fullname_str_mv b17cebaf09b4d737b9378a3581e3de93_***_Steven Kelly
author Steven Kelly
author2 James O’Connor-Moneley
Jessica Fletcher
Cody Bean
Josie Parker
Steven Kelly
Gary P. Moran
Derek J. Sullivan
format Journal article
container_title PLOS ONE
container_volume 19
container_issue 8
container_start_page e0308665
publishDate 2024
institution Swansea University
issn 1932-6203
doi_str_mv 10.1371/journal.pone.0308665
publisher Public Library of Science (PLoS)
college_str Faculty of Medicine, Health and Life Sciences
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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 - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 0
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description Development of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Mediator complex which is involved in the global control of transcription. This study investigates the acquisition of fluconazole tolerance in a mutant in which the entire TLO gene family has been deleted. This phenotype was reversed to varying degrees upon reintroduction of representative members of the alpha- and beta-TLO clades (i.e. TLO1 and TLO2), but not by TLO11, a gamma-clade representative. Comparative RNA sequencing analysis revealed changes in the expression of genes involved in a range of cellular functions, including ergosterol biosynthesis, mitochondrial function, and redox homeostasis. This was supported by the results of mass spectrometry analysis, which revealed alterations in sterol composition of the mutant cell membrane. Our data suggest that members of the C. albicans TLO gene family are involved in the control of ergosterol biosynthesis and mitochondrial function and may play a role in the responses of C. albicans to azole antifungal agents.
published_date 2024-08-09T14:44:18Z
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