Frédéric ArieyBenoit WitkowskiChanaki AmaratungaJohann BeghainAnne Claire LangloisNimol KhimSaorin KimValentine DuruChristiane BouchierLaurence MaPharath LimRithea LeangSocheat DuongSokunthea SrengSeila SuonChar Meng ChuorDenis Mey BoutSandie MénardWilliam O. RogersBlaise GentonThierry FandeurOlivo MiottoPascal RingwaldJacques Le BrasAntoine BerryJean Christophe BaraleRick M. FairhurstFrançoise Benoit-VicalOdile Mercereau-PuijalonDidier MénardInstitut Pasteur, ParisCNRS Centre National de la Recherche ScientifiqueInstitut Pasteur du CambodgeNational Institute of Allergy and Infectious DiseasesNational Center for Parasitology, Entomology and Malaria ControlCHU de ToulouseNaval Medical Research Unit-2Swiss Tropical and Public Health Institute (Swiss TPH)University of OxfordMahidol UniversityWellcome Trust Sanger InstituteOrganisation Mondiale de la SanteHopital Bichat-Claude-Bernard AP-HPUniversite de Toulouse2018-11-092018-11-092014-01-01Nature. Vol.505, No.7481 (2014), 50-5514764687002808362-s2.0-84892372929https://repository.li.mahidol.ac.th/handle/123456789/34983Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7-1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread. © 2014 Macmillan Publishers Limited.Mahidol UniversityMultidisciplinaryArticleSCOPUS10.1038/nature12876