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Plasmodium falciparum: multifaceted resistance to artemisinins

Abstract : AbstractPlasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is due to mutation of the PfK13 propeller domain and involves an unconventional mechanism based on a quiescence state leading to parasite recrudescence as soon as drug pressure is removed. The enhanced P. falciparum quiescence capacity of artemisinin-resistant parasites results from an increased ability to manage oxidative damage and an altered cell cycle gene regulation within a complex network involving the unfolded protein response, the PI3K/PI3P/AKT pathway, the PfPK4/eIF2α cascade and yet unidentified transcription factor(s), with minimal energetic requirements and fatty acid metabolism maintained in the mitochondrion and apicoplast. The detailed study of these mechanisms offers a way forward for identifying future intervention targets to fend off established artemisinin resistance.
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Lucie Paloque, Arba Ramadani, Odile Mercereau-Puijalon, Jean-Michel Augereau, Françoise Benoit-Vical. Plasmodium falciparum: multifaceted resistance to artemisinins. Malaria Journal, BioMed Central, 2016, 15 (1), pp.149/1-12. ⟨10.1186/s12936-016-1206-9⟩. ⟨inserm-01322524⟩

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