Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system
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 p...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320720300324 |
| _version_ | 1819203621984665600 |
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| author | Maria Grechnikova Kateřina Ženíšková Ronald Malych Jan Mach Robert Sutak |
| author_facet | Maria Grechnikova Kateřina Ženíšková Ronald Malych Jan Mach Robert Sutak |
| author_sort | Maria Grechnikova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T04:22:50Z |
| format | Article |
| id | doaj.art-6e196d06226d458d88f3a5320622dc9f |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-12-23T04:22:50Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-6e196d06226d458d88f3a5320622dc9f2022-12-21T18:00:12ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072020-12-0114126135Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant systemMaria Grechnikova0Kateřina Ženíšková1Ronald Malych2Jan Mach3Robert Sutak4Department of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech RepublicDepartment of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech RepublicDepartment of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech RepublicDepartment of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech RepublicCorresponding author.; Department of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech RepublicCopper 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.http://www.sciencedirect.com/science/article/pii/S2211320720300324CopperOxidative stressCopper-translocating ATPaseNaegleria fowleriIonophoresHemerythrin |
| spellingShingle | Maria Grechnikova Kateřina Ženíšková Ronald Malych Jan Mach Robert Sutak Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system International Journal for Parasitology: Drugs and Drug Resistance Copper Oxidative stress Copper-translocating ATPase Naegleria fowleri Ionophores Hemerythrin |
| title | Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system |
| title_full | Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system |
| title_fullStr | Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system |
| title_full_unstemmed | Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system |
| title_short | Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system |
| title_sort | copper detoxification machinery of the brain eating amoeba naegleria fowleri involves copper translocating atpase and the antioxidant system |
| topic | Copper Oxidative stress Copper-translocating ATPase Naegleria fowleri Ionophores Hemerythrin |
| url | http://www.sciencedirect.com/science/article/pii/S2211320720300324 |
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