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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-05-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/51015 |
| _version_ | 1811253272559747072 |
|---|---|
| author | Luana C Mathieu Horace Cox Angela M Early Sachel Mok Yassamine Lazrek Jeanne-Celeste Paquet Maria-Paz Ade Naomi W Lucchi Quacy Grant Venkatachalam Udhayakumar Jean SF Alexandre Magalie Demar Pascal Ringwald Daniel E Neafsey David A Fidock Lise Musset |
| author_facet | Luana C Mathieu Horace Cox Angela M Early Sachel Mok Yassamine Lazrek Jeanne-Celeste Paquet Maria-Paz Ade Naomi W Lucchi Quacy Grant Venkatachalam Udhayakumar Jean SF Alexandre Magalie Demar Pascal Ringwald Daniel E Neafsey David A Fidock Lise Musset |
| author_sort | Luana C Mathieu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T16:48:26Z |
| format | Article |
| id | doaj.art-c827568158c04d0c8f054f163d27f21d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:48:26Z |
| publishDate | 2020-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c827568158c04d0c8f054f163d27f21d2022-12-22T03:24:30ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.51015Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistanceLuana C Mathieu0https://orcid.org/0000-0002-6021-468XHorace Cox1Angela M Early2Sachel Mok3https://orcid.org/0000-0002-9605-0154Yassamine Lazrek4Jeanne-Celeste Paquet5https://orcid.org/0000-0001-6046-0154Maria-Paz Ade6Naomi W Lucchi7Quacy Grant8Venkatachalam Udhayakumar9Jean SF Alexandre10Magalie Demar11Pascal Ringwald12Daniel E Neafsey13https://orcid.org/0000-0002-1665-9323David A Fidock14https://orcid.org/0000-0001-6753-8938Lise Musset15https://orcid.org/0000-0003-0215-4110Laboratoire de parasitologie, Centre Nationale de Référence du Paludisme, World Health Organization Collaborating Center for surveillance of antimalarial drug resistance, Institut Pasteur de la Guyane, Cayenne, French Guiana; Ecole Doctorale n°587, Diversités, Santé, et Développement en Amazonie, Université de Guyane, Cayenne, French GuianaMinistry of Public Health, Georgetown, GuyanaBroad Institute of MIT and Harvard, Cambridge, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United StatesDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, United StatesLaboratoire de parasitologie, Centre Nationale de Référence du Paludisme, World Health Organization Collaborating Center for surveillance of antimalarial drug resistance, Institut Pasteur de la Guyane, Cayenne, French GuianaDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, United StatesDepartment of Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization, Washington, United StatesMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, United StatesMinistry of Public Health, Georgetown, GuyanaMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, United StatesPan American Health Organization, Georgetown, GuyanaService de Maladies Infectieuses et Tropicales, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana; Ecosystèmes Amazoniens et Pathologie Tropicale (EPAT), EA3593, Université de Guyane, Cayenne, French GuianaGlobal Malaria Program, World Health Organization, Geneva, SwitzerlandBroad Institute of MIT and Harvard, Cambridge, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United StatesDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, United States; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, United StatesLaboratoire de parasitologie, Centre Nationale de Référence du Paludisme, World Health Organization Collaborating Center for surveillance of antimalarial drug resistance, Institut Pasteur de la Guyane, Cayenne, French GuianaAntimalarial 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.https://elifesciences.org/articles/51015Guyanaartemisinin resistanceevolutionkelch 13South Americamalaria |
| spellingShingle | Luana C Mathieu Horace Cox Angela M Early Sachel Mok Yassamine Lazrek Jeanne-Celeste Paquet Maria-Paz Ade Naomi W Lucchi Quacy Grant Venkatachalam Udhayakumar Jean SF Alexandre Magalie Demar Pascal Ringwald Daniel E Neafsey David A Fidock Lise Musset Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance eLife Guyana artemisinin resistance evolution kelch 13 South America malaria |
| 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 | Guyana artemisinin resistance evolution kelch 13 South America malaria |
| url | https://elifesciences.org/articles/51015 |
| work_keys_str_mv | AT luanacmathieu localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT horacecox localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT angelamearly localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT sachelmok localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT yassaminelazrek localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT jeannecelestepaquet localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT mariapazade localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT naomiwlucchi localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT quacygrant localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT venkatachalamudhayakumar localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT jeansfalexandre localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT magaliedemar localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT pascalringwald localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT danieleneafsey localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT davidafidock localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance AT lisemusset localemergenceinamazoniaofplasmodiumfalciparumk13c580ymutantsassociatedwithinvitroartemisininresistance |