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Investigating the Colonisation of Voice Prostheses by Candida albicans Following Total Laryngectomy

Pentland, Daniel (2019) Investigating the Colonisation of Voice Prostheses by Candida albicans Following Total Laryngectomy. Doctor of Philosophy (PhD) thesis, University of Kent,. (KAR id:81199)

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Abstract

A total laryngectomy is a surgical procedure for the treatment of advanced laryngeal cancer. The vocal cords are removed during the procedure, leaving patients with an inability to form speech. The gold standard of speech rehabilitation involves the use of small silicone valves called voice prostheses (VPs) which are inserted into the throat. C. albicans is a major coloniser of VPs, often being found in polymicrobial biofilms, causing loss of device function as well as creating a reservoir for infections. As a result, VPs have to be regularly changed at great patient stress and clinical cost. In this study, we present precision antifungal-focussed treatment guidelines which significantly increase VP in situ lifespan from a mean of 71.9 to 192.0 days, a 2.7-fold increase, in a 20 patient cohort. In addition, we find that the high CO2 environment of the throat (due to the CO2 content of exhaled breath) increases the biofilm-forming capacity of C. albicans. All stages of biofilm growth (attachment, maturation and dispersal) are enhanced in 5% CO2 and this is accompanied by increased antifungal tolerance; providing a possible explanation for the success of C. albicans in the VP niche. Finally, we explore potential treatment options for high CO2 biofilms, identifying the glycolytic inhibitor 2-deoxyglucose as a promising candidate. Overall, our study characterises a clinically relevant CO2-mediated increase in C. albicans biofilm formation which could influence future biofilm studies and therapeutic discovery.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Gourlay, Campbell
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 13 May 2020 09:10 UTC
Last Modified: 20 May 2021 13:25 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/81199 (The current URI for this page, for reference purposes)
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