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|Title:||K13-mediated reduced susceptibility to artemisinin in Plasmodium falciparum is overlaid on a trait of enhanced DNA damage repair||Authors:||Xiong, Aoli
Tay, Ian Jun Jie
Woodrow, Charles J.
Engelward, Bevin P.
Preiser, Peter Rainer
|Keywords:||Science::Biological sciences||Issue Date:||2020||Source:||Xiong, A., Prakash, P., Gao, X., Chew, M., Tay, I. J. J., Woodrow, C. J., . . . Preiser, P. R. (2020). K13-mediated reduced susceptibility to artemisinin in Plasmodium falciparum is overlaid on a trait of enhanced DNA damage repair. Cell Reports, 32(5), 107996-. doi:10.1016/j.celrep.2020.107996||Journal:||Cell Reports||Abstract:||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.||URI:||https://hdl.handle.net/10356/146590||ISSN:||2211-1247||DOI:||10.1016/j.celrep.2020.107996||Schools:||School of Biological Sciences||Rights:||© 2020 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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