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Article Dans Une Revue Cell Reports Année : 2022

Human peroxiredoxin 6 is essential for malaria parasites and provides a host-based drug target

Sheldon I Feinstein
  • Fonction : Auteur

Résumé

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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hal-03790129 , version 1 (28-09-2022)

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Matthias Paulus Wagner, Pauline Formaglio, Olivier Gorgette, Jerzy Michal Dziekan, Christèle Huon, et al.. Human peroxiredoxin 6 is essential for malaria parasites and provides a host-based drug target. Cell Reports, 2022, 39 (11), pp.110923. ⟨10.1016/j.celrep.2022.110923⟩. ⟨hal-03790129⟩
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