Article
Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum.
Nature communications - 27 May 2023
Kümpornsin Krittikorn, Kochakarn Theerarat, Yeo Tomas, Okombo John, Luth Madeline R, Hoshizaki Johanna, Rawat Mukul, Pearson Richard D, Schindler Kyra A, Mok Sachel, Park Heekuk, Uhlemann Anne-Catrin, Jana Gouranga P, Maity Bikash C, Laleu Benoît, Chenu Elodie, Duffy James, Moliner Cubel Sonia, Franco Virginia, Gomez-Lorenzo Maria G, Gamo Francisco Javier, Winzeler Elizabeth A, Fidock David A, Chookajorn Thanat, Lee Marcus C S
Abstract excerpt
In vitro evolution of drug resistance is a powerful approach for identifying antimalarial targets, however, key obstacles to eliciting resistance are the parasite inoculum size and mutation rate. Here we sought to increase parasite genetic diversity to potentiate resistance selections by editing catalytic residues of Plasmodium falciparum DNA polymerase δ. Mutation accumulation assays reveal a ~5-8 fold elevation...
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