| First Author | Wagner MP | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 11 | Pages | 110923 |
| PubMed ID | 35705035 | Mgi Jnum | J:332074 |
| Mgi Id | MGI:7311484 | Doi | 10.1016/j.celrep.2022.110923 |
| Citation | Wagner MP, et al. (2022) Human peroxiredoxin 6 is essential for malaria parasites and provides a host-based drug target. Cell Rep 39(11):110923 |
| abstractText | 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. |
