Human peroxiredoxin 6 is essential for malaria parasites and provides a host-based drug target
In: Cell Reports, Jg. 39 (2022), Heft 11, S. 110923-
Online
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Zugriff:
Summary: The uptake and digestion of host hemoglobin by malaria parasites during blood-stage growth leads to significant oxidative damage of membrane lipids. Repair of lipid peroxidation damage is crucial for parasite survival. Here, we demonstrate that Plasmodium falciparum imports a host antioxidant enzyme, peroxiredoxin 6 (PRDX6), during hemoglobin uptake from the red blood cell cytosol. PRDX6 is a lipid-peroxidation repair enzyme with phospholipase A2 (PLA2) activity. Inhibition of PRDX6 with a PLA2 inhibitor, Darapladib, increases lipid-peroxidation damage in the parasite and disrupts transport of hemoglobin-containing vesicles to the food vacuole, causing parasite death. Furthermore, inhibition of PRDX6 synergistically reduces the survival of artemisinin-resistant parasites following co-treatment of parasite cultures with artemisinin and Darapladib. Thus, PRDX6 is a host-derived drug target for development of antimalarial drugs that could help overcome artemisinin resistance.
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Human peroxiredoxin 6 is essential for malaria parasites and provides a host-based drug target
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Autor/in / Beteiligte Person: | Matthias Paulus Wagner ; Formaglio, Pauline ; Gorgette, Olivier ; Jerzy Michal Dziekan ; Huon, Christèle ; Berneburg, Isabell ; Rahlfs, Stefan ; Barale, Jean-Christophe ; Feinstein, Sheldon I. ; Fisher, Aron B. ; Ménard, Didier ; Bozdech, Zbynek ; Amino, Rogerio ; Touqui, Lhousseine ; Chitnis, Chetan E. |
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Zeitschrift: | Cell Reports, Jg. 39 (2022), Heft 11, S. 110923- |
Veröffentlichung: | Elsevier, 2022 |
Medientyp: | academicJournal |
ISSN: | 2211-1247 (print) |
DOI: | 10.1016/j.celrep.2022.110923 |
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