title: Plasmodium falciparum: multifaceted resistance to artemisinins.
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 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.
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination) UPR8241, 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France. lucie.paloque@lcc-toulouse.fr.|Université de Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France. lucie.paloque@lcc-toulouse.fr.
authors.forename: Lucie
authors.initials: L
authors.lastname: Paloque
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination) UPR8241, 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France. pramundita_a1@yahoo.com.|Université de Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France. pramundita_a1@yahoo.com.|Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia. pramundita_a1@yahoo.com.
authors.forename: Arba P
authors.initials: AP
authors.lastname: Ramadani
authors.affiliation: Unité d'Immunologie Moléculaire des Parasites, Institut Pasteur, 75015, Paris, France. odile.puijalon@pasteur.fr.
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination) UPR8241, 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France. jean-michel.augereau@lcc-toulouse.fr.|Université de Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France. jean-michel.augereau@lcc-toulouse.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Augereau
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination) UPR8241, 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France. francoise.vical@inserm.fr.|Université de Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France. francoise.vical@inserm.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Benoit-Vical
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics
chemical_list: D000962:Antimalarials; D037621:Artemisinins