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

Tytuł:: Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system.
Autorzy:: Copsey AC; Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.
Barsottini MRO; Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.
May B; Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.; Theradex (Europe) Ltd, 2nd Floor, The Pinnacle, Station Way, Crawley, RH10 1JH, UK.
Xu F; Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.; Applied Biotechnology Center, Wuhan University of Bioengineering, Wuhan, China.
Albury MS; Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.
Young L; Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.
Moore AL; Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK. .
Źródło:: Scientific reports [Sci Rep] 2021 Jul 20; Vol. 11 (1), pp. 14748. Date of Electronic Publication: 2021 Jul 20.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:: Drug Resistance, Fungal*
Candida albicans/*enzymology
Fungal Proteins/*metabolism
Liposomes/*metabolism
Mitochondrial Proteins/*metabolism
Oxidoreductases/*metabolism
Plant Proteins/*metabolism
Antifungal Agents/pharmacology ; Enzyme Inhibitors/pharmacology ; Fungal Proteins/antagonists & inhibitors ; Fungal Proteins/genetics ; Kinetics ; Mitochondrial Proteins/antagonists & inhibitors ; Mitochondrial Proteins/genetics ; Oxidoreductases/antagonists & inhibitors ; Oxidoreductases/genetics ; Plant Proteins/antagonists & inhibitors ; Plant Proteins/genetics ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism
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Grant Information:: BB/L022915/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council
Substance Nomenclature:: 0 (Antifungal Agents)
0 (Enzyme Inhibitors)
0 (Fungal Proteins)
0 (Liposomes)
0 (Mitochondrial Proteins)
0 (Plant Proteins)
0 (Recombinant Proteins)
EC 1.- (Oxidoreductases)
EC 1.- (alternative oxidase)
Entry Date(s):: Date Created: 20210721 Date Completed: 20210729 Latest Revision: 20240402
Update Code:: 20240402
PubMed Central ID:: PMC8292455
DOI:: 10.1038/s41598-021-94320-3
PMID:: 34285303
: Czasopismo naukowe

Pełny tekst

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.
(© 2021. The Author(s).)

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