Plasmodium falciparum: multifaceted resistance to artemisinins. (December 2016)

• Record Type: Journal Article
• Authors: Paloque, Lucie; Ramadani, Arba; Mercereau-Puijalon, Odile; Augereau, Jean-Michel; Benoit-Vical, Françoise
• Is Part Of: Malaria journal. Volume 15:Number 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: Malaria -- Artemisinin-based combination therapy -- Resistance -- PfK13 -- Quiescence; Malaria -- Periodicals; 616.9362
• DOI: 10.1186/s12936-016-1206-9
• Languages: English
• ISSNs: 1475-2875

Abstract

Abstract Plasmodium 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 enhancedP. 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.