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Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance

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...

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Autores principales: Mathieu, Luana C, Cox, Horace, Early, Angela M, Mok, Sachel, Lazrek, Yassamine, Paquet, Jeanne-Celeste, Ade, Maria-Paz, Lucchi, Naomi W, Grant, Quacy, Udhayakumar, Venkatachalam, Alexandre, Jean SF, Demar, Magalie, Ringwald, Pascal, Neafsey, Daniel E, Fidock, David A, Musset, Lise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217694/
https://www.ncbi.nlm.nih.gov/pubmed/32394893
http://dx.doi.org/10.7554/eLife.51015
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author Mathieu, Luana C
Cox, Horace
Early, Angela M
Mok, Sachel
Lazrek, Yassamine
Paquet, Jeanne-Celeste
Ade, Maria-Paz
Lucchi, Naomi W
Grant, Quacy
Udhayakumar, Venkatachalam
Alexandre, Jean SF
Demar, Magalie
Ringwald, Pascal
Neafsey, Daniel E
Fidock, David A
Musset, Lise
author_facet Mathieu, Luana C
Cox, Horace
Early, Angela M
Mok, Sachel
Lazrek, Yassamine
Paquet, Jeanne-Celeste
Ade, Maria-Paz
Lucchi, Naomi W
Grant, Quacy
Udhayakumar, Venkatachalam
Alexandre, Jean SF
Demar, Magalie
Ringwald, Pascal
Neafsey, Daniel E
Fidock, David A
Musset, Lise
author_sort Mathieu, Luana C
collection PubMed
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.
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spelling pubmed-72176942020-05-13 Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance Mathieu, Luana C Cox, Horace Early, Angela M Mok, Sachel Lazrek, Yassamine Paquet, Jeanne-Celeste Ade, Maria-Paz Lucchi, Naomi W Grant, Quacy Udhayakumar, Venkatachalam Alexandre, Jean SF Demar, Magalie Ringwald, Pascal Neafsey, Daniel E Fidock, David A Musset, Lise eLife Epidemiology and Global Health 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. eLife Sciences Publications, Ltd 2020-05-12 /pmc/articles/PMC7217694/ /pubmed/32394893 http://dx.doi.org/10.7554/eLife.51015 Text en © 2020, Mathieu et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Epidemiology and Global Health
Mathieu, Luana C
Cox, Horace
Early, Angela M
Mok, Sachel
Lazrek, Yassamine
Paquet, Jeanne-Celeste
Ade, Maria-Paz
Lucchi, Naomi W
Grant, Quacy
Udhayakumar, Venkatachalam
Alexandre, Jean SF
Demar, Magalie
Ringwald, Pascal
Neafsey, Daniel E
Fidock, David A
Musset, Lise
Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance
title Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance
title_full Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance
title_fullStr Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance
title_full_unstemmed Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance
title_short Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance
title_sort local emergence in amazonia of plasmodium falciparum k13 c580y mutants associated with in vitro artemisinin resistance
topic Epidemiology and Global Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217694/
https://www.ncbi.nlm.nih.gov/pubmed/32394893
http://dx.doi.org/10.7554/eLife.51015
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