K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates

The emergence of artemisinin resistance in Southeast Asia imperils efforts to reduce the global malaria burden. We genetically modified the Plasmodium falciparum K13 locus using zinc-finger nucleases and measured ring-stage survival rates after drug exposure in vitro; these rates correlate with parasite clearance half-lives in artemisinin-treated patients. With isolates from Cambodia, where resistance first emerged, survival rates decreased from 13 to 49% to 0.3 to 2.4% after the removal of K13 mutations. Conversely, survival rates in wild-type parasites increased from ≤0.6% to 2 to 29% after the insertion of K13 mutations. These mutations conferred elevated resistance to recent Cambodian isolates compared…

• AN
  Agence Nationale de la Recherche

  Award: ANR-13-BSV3-0018-01
• NI
  National Institutes of Health

  Award: R01 AI109023
• NI
  National Institute of Allergy and Infectious Diseases