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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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Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
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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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Journal Article
Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system
2021
Overview
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 (K
m
and V
max
) 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Antifungal Agents - pharmacology
/ Candida albicans - enzymology
/ COVID-19
/ Enzyme Inhibitors - pharmacology
/ Fungal Proteins - antagonists & inhibitors
/ Fungal Proteins - metabolism
/ Humanities and Social Sciences
/ Kinetics
/ Mitochondrial Proteins - antagonists & inhibitors
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - metabolism
/ Oxidoreductases - antagonists & inhibitors
/ Oxidoreductases - metabolism
/ Plant Proteins - antagonists & inhibitors
/ Recombinant Proteins - genetics
/ Recombinant Proteins - metabolism
/ Science
