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

Cell Reports, ISSN: 2211-1247, Vol: 39, Issue: 11, Page: 110923
2022
  • 12
    Citations
  • 0
    Usage
  • 48
    Captures
  • 1
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    12
  • Captures
    48
  • Mentions
    1
    • References
      1
      • Wikipedia
        1

Article Description

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 A 2 (PLA 2 ) activity. Inhibition of PRDX6 with a PLA 2 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.

Bibliographic Details

Wagner, Matthias Paulus; Formaglio, Pauline; Gorgette, Olivier; Dziekan, Jerzy Michal; 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

Elsevier BV

Biochemistry, Genetics and Molecular Biology

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