Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system.
Copper
Copper-translocating ATPase
Hemerythrin
Ionophores
Naegleria fowleri
Oxidative stress
Journal
International journal for parasitology. Drugs and drug resistance
ISSN: 2211-3207
Titre abrégé: Int J Parasitol Drugs Drug Resist
Pays: Netherlands
ID NLM: 101576715
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
05
06
2020
revised:
29
09
2020
accepted:
02
10
2020
pubmed:
24
10
2020
medline:
21
8
2021
entrez:
23
10
2020
Statut:
ppublish
Résumé
Copper is a trace metal that is necessary for all organisms but toxic when present in excess. Different mechanisms to avoid copper toxicity have been reported to date in pathogenic organisms such as Cryptococcus neoformans and Candida albicans. However, little if anything is known about pathogenic protozoans despite their importance in human and veterinary medicine. Naegleria fowleri is a free-living amoeba that occurs naturally in warm fresh water and can cause a rapid and deadly brain infection called primary amoebic meningoencephalitis (PAM). Here, we describe the mechanisms employed by N. fowleri to tolerate high copper concentrations, which include various strategies such as copper efflux mediated by a copper-translocating ATPase and upregulation of the expression of antioxidant enzymes and obscure hemerythrin-like and protoglobin-like proteins. The combination of different mechanisms efficiently protects the cell and ensures its high copper tolerance, which can be advantageous both in the natural environment and in the host. Nevertheless, we demonstrate that copper ionophores are potent antiamoebic agents; thus, copper metabolism may be considered a therapeutic target.
Identifiants
pubmed: 33096396
pii: S2211-3207(20)30032-4
doi: 10.1016/j.ijpddr.2020.10.001
pmc: PMC7578549
pii:
doi:
Substances chimiques
Antioxidants
0
Copper
789U1901C5
Adenosine Triphosphatases
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
126-135Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
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