Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system. (December 2020)

• Record Type: Journal Article
• Authors: Grechnikova, Maria; Ženíšková, Kateřina; Malych, Ronald; Mach, Jan; Sutak, Robert
• Is Part Of: International journal for parasitology. Volume 14(2020)
• Page Start: 126
• Page End: 135
• Publication Date: 2020-12
• Subjects: Copper -- Oxidative stress -- Copper-translocating ATPase -- Naegleria fowleri -- Ionophores -- Hemerythrin; Parasitic diseases -- Chemotherapy -- Periodicals; Drug resistance -- Periodicals; 616.96061
• DOI: 10.1016/j.ijpddr.2020.10.001
• Languages: English
• ISSNs: 2211-3207

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: N. fowleri employs the combination of copper efflux and antioxidant system to ensure a high copper tolerance. Copper efflux in N. fowleri is mediated by a copper-translocating P-type ATPase. Copper ionophores have amoebicidal effect against N. fowleri and thus may be potentially used as antiamoebic agents. Iron-binding proteins hemerythrin and protoglobin are highly upregulated in N. fowleri under copper overload.