期刊
CELL REPORTS
卷 32, 期 5, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.107996
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资金
- National Research Foundation, Prime Minister's Office, Singapore, through the Singapore-MIT Alliance for Research and Technology (SMART) BioSystems and Micromechanics (BioSym) Interdisciplinary Research Group (IRG)
- National Research Foundation, Prime Minister's Office, Singapore, through Antimicrobial Resistance IRG
- Bill and Melinda Gates Foundation (Global Health grant) [OPP1040463]
- Bill and Melinda Gates Foundation [OPP1040463] Funding Source: Bill and Melinda Gates Foundation
Southeast Asia has been the hotbed for the development of drug-resistant malaria parasites, including those with resistance to artemisinin combination therapy. While mutations in the kelch propeller domain (K13 mutations) are associated with artemisinin resistance, a range of evidence suggests that other factors are critical for the establishment and subsequent transmission of resistance in the field. Here, we perform a quantitative analysis of DNA damage and repair in the malaria parasite Plasmodium falciparum and find a strong link between enhanced DNA damage repair and artemisinin resistance. This experimental observation is further supported when variations in seven known DNA repair genes are found in resistant parasites, with six of these mutations being associated with K13 mutations. Our data provide important insights on confounding factors that are important for the establishment and spread of artemisinin resistance and may explain why resistance has not yet arisen in Africa.
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