Copsey 2021 Sci Rep

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Copsey AC, Barsottini MRO, May B, Xu F, Albury MS, Young L, Moore AL (2021) Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system. Sci Rep 11:14748.

» PMID: 34285303 Open Access

Copsey Alice C, Barsottini Mario R O, May Benjamin, Xu Fei, Albury Mary S, Young Luke, Moore Anthony L (2021) Sci Rep

Abstract: Candidemia 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.

© 2021. The Author(s).

Bioblast editor: Plangger M O2k-Network Lab: UK Brighton Moore AL


Labels: MiParea: Respiration  Pathology: Infectious 

Organism: Fungi 




HRR: Oxygraph-2k, NextGen-O2k 

2021, AOX