Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system

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 t...

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Autores principales:	Alice C. Copsey, Mario R. O. Barsottini, Benjamin May, Fei Xu, Mary S. Albury, Luke Young, Anthony L. Moore
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b73a77007db41e9a3dd08b4d3ca64d7
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spelling	oai:doaj.org-article:8b73a77007db41e9a3dd08b4d3ca64d72021-12-02T16:17:21ZKinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system10.1038/s41598-021-94320-32045-2322https://doaj.org/article/8b73a77007db41e9a3dd08b4d3ca64d72021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94320-3https://doaj.org/toc/2045-2322Abstract 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.Alice C. CopseyMario R. O. BarsottiniBenjamin MayFei XuMary S. AlburyLuke YoungAnthony L. MooreNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alice C. Copsey Mario R. O. Barsottini Benjamin May Fei Xu Mary S. Albury Luke Young Anthony L. Moore Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
description	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.
format	article
author	Alice C. Copsey Mario R. O. Barsottini Benjamin May Fei Xu Mary S. Albury Luke Young Anthony L. Moore
author_facet	Alice C. Copsey Mario R. O. Barsottini Benjamin May Fei Xu Mary S. Albury Luke Young Anthony L. Moore
author_sort	Alice C. Copsey
title	Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
title_short	Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
title_full	Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
title_fullStr	Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
title_full_unstemmed	Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
title_sort	kinetic characterisation and inhibitor sensitivity of candida albicans and candida auris recombinant aox expressed in a self-assembled proteoliposome system
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8b73a77007db41e9a3dd08b4d3ca64d7
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Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system

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