Copsey 2021 Sci Rep

From Bioblast
Publications in the MiPMap
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.

Β» 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.

Β© 2021. The Author(s).

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

Labels: MiParea: Respiration  Pathology: Infectious 

Organism: Fungi 

HRR: Oxygraph-2k, NextGen-O2k 

2021, AOX 

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