Integrative Genetic Manipulation of Plasmodium cynomolgi Reveals Multidrug Resistance-1 Y976F Associated With Increased In Vitro Susceptibility to Mefloquine

The lack of a long-term in vitro culture method has severely restricted the study of Plasmodium vivax, in part because it limits genetic manipulation and reverse genetics. We used the recently optimized Plasmodium cynomolgi Berok in vitro culture model to investigate the putative P. vivax drug resis...

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Detalles Bibliográficos
Autores principales: Ward, Kurt E, Christensen, Peter, Racklyeft, Annie, Dhingra, Satish K, Chua, Adeline C Y, Remmert, Caroline, Suwanarusk, Rossarin, Matheson, Jessica, Blackman, Michael J, Kaneko, Osamu, Kyle, Dennis E, Lee, Marcus C S, Moon, Robert W, Snounou, Georges, Rénia, Laurent, Fidock, David A, Russell, Bruce, Bifani, Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Major Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175063/
https://www.ncbi.nlm.nih.gov/pubmed/36478252
http://dx.doi.org/10.1093/infdis/jiac469
Descripción
Sumario:The lack of a long-term in vitro culture method has severely restricted the study of Plasmodium vivax, in part because it limits genetic manipulation and reverse genetics. We used the recently optimized Plasmodium cynomolgi Berok in vitro culture model to investigate the putative P. vivax drug resistance marker MDR1 Y976F. Introduction of this mutation using clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 9 (CRISPR-Cas9) increased sensitivity to mefloquine, but had no significant effect on sensitivity to chloroquine, amodiaquine, piperaquine, and artesunate. To our knowledge, this is the first reported use of CRISPR-Cas9 in P. cynomolgi, and the first reported integrative genetic manipulation of this species.

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