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

Author:

Straimer Judith1,Gnädig Nina F.1,Witkowski Benoit2,Amaratunga Chanaki3,Duru Valentine2,Ramadani Arba Pramundita45,Dacheux Mélanie1,Khim Nimol2,Zhang Lei6,Lam Stephen6,Gregory Philip D.6,Urnov Fyodor D.6,Mercereau-Puijalon Odile7,Benoit-Vical Françoise45,Fairhurst Rick M.3,Ménard Didier2,Fidock David A.18

Affiliation:

1. Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

2. Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.

3. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

4. Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie de Coordination UPR8241, Toulouse, France.

5. Université de Toulouse, UPS, Institut National Polytechnique de Toulouse, Toulouse, France.

6. Sangamo BioSciences, Richmond, CA, USA.

7. Institut Pasteur, Parasite Molecular Immunology Unit, Paris, France.

8. Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.

Abstract

Mechanisms propelling drug resistance If it were to spread, resistance to the drug artemisinin would seriously derail the recent gains of global malaria control programs (see the Perspective by Sibley). Mutations in a region called the K13-propeller are predictive for artemisinin resistance in Southeast Asia. Mok et al. looked at the patterns of gene expression in parasites isolated from more than 1000 patients sampled in Africa, Bangladesh, and the Mekong region. A range of mutations that alter protein repair pathways and the timing of the parasite's developmental cycle were only found in parasites from the Mekong region. Straimer et al. genetically engineered the K13 region of parasites obtained from recent clinical isolates. Mutations in this region were indeed responsible for the resistance phenotypes. Science , this issue p. 431 , p. 428 ; see also p. 373

Funder

NIH

National Institute of Allergy and Infectious Diseases

Agence Nationale de la Recherche

Institut Pasteur, Division International

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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