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Investigating the potential of Succinate dehydrogenase as an anti-fungal drug target in Candida glabrata

Currie, Andrew (2021) Investigating the potential of Succinate dehydrogenase as an anti-fungal drug target in Candida glabrata. Master of Research (MRes) thesis, University of Kent,. (doi:10.22024/UniKent/01.02.86837) (KAR id:86837)

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Official URL
https://doi.org/10.22024/UniKent/01.02.86837

Abstract

Candida glabrata is an opportunist human fungal pathogen which causes disease in immuno-compromised patients and is highly drug resistant to commonly prescribed anti-fungal drugs such as Fluconazole. This project tested whether Lonidamine (LND) has potential as a new antifungal agent. LND has shown to be safe in the mouse model so suggests it can be used in humans and has also recently been shown to inhibit Succinate dehydrogenase (complex II of the mitochondrial respiratory chain). LND caused a reduction in the C. glabrata biofilm and its ability to form colonies. Flocculation during growth assays suggested that LND causes disruptions of the cell wall. Respirometry analysis suggested LND does not utilise the ETC when SDH is inhibited and relies on the compensatory metabolic pathway known as the glyoxylate cycle. Through S. cerevisiae mutant studies, weak points within metabolic pathways were found to be ICL1 (within the glyoxylate cycle) and LSC2 (within the TCA cycle). Future research on combinational drug therapy of using LND alongside inhibitors of ICL1 or LSC2 would be crucial.

Item Type: Thesis (Master of Research (MRes))
Thesis advisor: Gourlay, Campbell
DOI/Identification number: 10.22024/UniKent/01.02.86837
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 03 Mar 2021 11:29 UTC
Last Modified: 19 May 2021 15:22 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/86837 (The current URI for this page, for reference purposes)
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