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

Abstract

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 with that of reference lines, suggesting a contemporary contribution of additional genetic factors. Our data provide a conclusive rationale for worldwide K13-propeller sequencing to identify and eliminate artemisinin-resistant parasites.

DOI: 10.1126/science.1260867

2 Figures and Tables

0100200201520162017
Citations per Year

333 Citations

Semantic Scholar estimates that this publication has 333 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Straimer2015DrugRK, title={Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates.}, author={Judith Straimer and Nina F Gn{\"a}dig and Benoit Witkowski and Chanaki Amaratunga and Valentine Duru and Arba Pramundita Ramadani and M{\'e}lanie Dacheux and Nimol Khim and Lei Zhang and Stephen Lam and Philip D Gregory and Fyodor D Urnov and Odile Mercereau-Puijalon and Françoise Benoit-Vical and Rick M Fairhurst and Didier M{\'e}nard and David A Fidock}, journal={Science}, year={2015}, volume={347 6220}, pages={428-31} }