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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Local emergence in amazonia of plasmodium falciparum K13 C580Y mutants associated with in vitro artemisinin resistance
eLife, Volume 9, Article e51015, Year 2020
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Description
Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y. We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016–2017. Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance. In vitro growth competition assays revealed a fitness cost associated with these pfk13 variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America. These data place local malaria control efforts at risk in the Guiana Shield. © Mathieu et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-fig1-data1.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-fig3-data1.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-fig4-data1.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-fig5-data1.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-fig5-figsupp1-data1.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-fig5-figsupp2-data1.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-code1.pl
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-code2.pl
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-code3.txt
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-supp1.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-supp2.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-supp3.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-supp4.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC7217694/bin/elife-51015-transrepform.docx
Authors & Co-Authors
Mathieu, Luana C.
French Guiana, Cayenne
Institut Pasteur de la Guyane
France, Cayenne
Université de Guyane
Cox, Horace
Guyana, Georgetown
Ministry of Health
Early, Angela M.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Harvard T.h. Chan School of Public Health
Mok, Sachel
United States, New York
Columbia University Irving Medical Center
Adé, María Paz
United States, Washington, D.c.
Pan American Health Organization
Lucchi, Naomi W.
United States, Atlanta
Centers for Disease Control and Prevention
Udhayakumar, Venkatachalam
United States, Atlanta
Centers for Disease Control and Prevention
Demar, Magalie Pierre
French Guiana, Cayenne
Centre Hospitalier Andree Rosemon
France, Cayenne
Université de Guyane
Ringwald, Pascal
Switzerland, Geneva
Organisation Mondiale de la Santé
Neafsey, Daniel E.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Harvard T.h. Chan School of Public Health
Fidock, David A.
United States, New York
Columbia University Irving Medical Center
Musset, Lise
French Guiana, Cayenne
Institut Pasteur de la Guyane
Statistics
Citations: 72
Authors: 12
Affiliations: 11
Identifiers
Doi:
10.7554/eLife.51015
ISSN:
2050084X
Research Areas
Genetics And Genomics
Infectious Diseases