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

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Ward, Kurt, E. | Christensen, Peter | Racklyeft, Annie | Dhingra, Satish, K. | Chua, Adeline, C. Y. | Remmert, Caroline | Suwanarusk, Rossarin | Matheson, Jessica | Blackman, Michael | Kaneko, Osamu | Kyle, Dennis, E. | Lee, Marcus, C. S. | Moon, Robert, W. | Snounou, Georges | Rénia, Laurent | Fidock, David, A. | Russell, Bruce | Bifani, Pablo

Edité par CCSD ; Oxford University Press -

Presented in part: 5th Meeting of the Singapore Malaria Network, SingMalNet2022, 23–25 February 2022, Singapore. International audience. 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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