Integrative genetic manipulation of $Plasmodium\ cynomolgi$ reveals multidrug resistance-1 Y976Ff associated with increased in vitro susceptibility to mefloquine - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Infectious Diseases Année : 2023

Integrative genetic manipulation of $Plasmodium\ cynomolgi$ reveals multidrug resistance-1 Y976Ff associated with increased in vitro susceptibility to mefloquine

Osamu Kaneko
  • Fonction : Auteur

Résumé

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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Dates et versions

hal-04254735 , version 1 (23-10-2023)

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Kurt E. Ward, Peter Christensen, Annie Racklyeft, Satish K. Dhingra, Adeline C. Y. Chua, et al.. Integrative genetic manipulation of $Plasmodium\ cynomolgi$ reveals multidrug resistance-1 Y976Ff associated with increased in vitro susceptibility to mefloquine. Journal of Infectious Diseases, 2023, 227 (10), pp.1121-1126. ⟨10.1093/infdis/jiac469⟩. ⟨hal-04254735⟩
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