Journal article 58 views
Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance
James O’Connor-Moneley,
Jessica Fletcher 
,
Cody Bean,
Josie Parker,
Steven Kelly,
Gary P. Moran,
Derek J. Sullivan
,
Cody Bean,
Josie Parker,
Steven Kelly,
Gary P. Moran,
Derek J. Sullivan
PLOS ONE, Volume: 19, Issue: 8, Start page: e0308665
Swansea University Author: Steven Kelly
Full text not available from this repository: check for access using links below.
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...
| Published in: | PLOS ONE |
|---|---|
| ISSN: | 1932-6203 |
| Published: |
Public Library of Science (PLoS)
2024
|
| Online Access: |
Check full text
|
| URI: | https://cronfa.swan.ac.uk/Record/cronfa67874 |
| 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 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. |
|---|---|
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
DJS - and GPM - Science Foundation Ireland 19/FFP/6422 www.sfi.ie |
| Issue: |
8 |
| Start Page: |
e0308665 |