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Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
journal contribution
posted on 2023-06-10, 00:54 authored by Alice CopseyAlice Copsey, Mario Ramos De Oliveira Barsottini, Benjamin May, Fei Xu, Mary Albury, Luke Young, Anthony MooreCandidemia caused by Candida spp. is a serious threat in hospital settings being a major cause of acquired infection and death and a possible contributor to Covid-19 mortality. Candidemia incidence has been rising worldwide following increases in fungicide-resistant pathogens highlighting the need for more effective antifungal agents with novel modes of action. The membrane-bound enzyme alternative oxidase (AOX) promotes fungicide resistance and is absent in humans making it a desirable therapeutic target. However, the lipophilic nature of the AOX substrate (ubiquinol-10) has hindered its kinetic characterisation in physiologically-relevant conditions. Here, we present the purification and expression of recombinant AOXs from C. albicans and C. auris in a self-assembled proteoliposome (PL) system. Kinetic parameters (Km and Vmax) with respect to ubiquinol-10 have been determined. The PL system has also been employed in dose–response assays with novel AOX inhibitors. Such information is critical for the future development of novel treatments for Candidemia.
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Publication status
- Published
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- Published version
Journal
Scientific ReportsISSN
2045-2322Publisher
Nature ResearchExternal DOI
Volume
11Page range
1-10Article number
a14748Event location
EnglandDepartment affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-09-09First Open Access (FOA) Date
2021-09-09First Compliant Deposit (FCD) Date
2021-09-09Usage metrics
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