Association study of Plasmodium falciparum Acetyl-CoA Synthetase Mutations S868G and V949I with antimalarial drugs

Wei Xia Zhao; Zheng Xiang; Weilin Zeng; Yucheng Qin; Maohua Pan; Yanrui Wu; Mengxi Duan; Ye Mou; Tao Liang; Yanmei Zhang; Cheng Liu; Xiuya Tang; Yaming Huang; Gongchao Yang; Liwang Cui; Zhaoqing Yang

doi:10.1101/2024.07.10.602966

MicrobiologybioRxivJul 10, 2024

Preprint

Association study of Plasmodium falciparum Acetyl-CoA Synthetase Mutations S868G and V949I with antimalarial drugs

Wei Xia Zhao iD, Zheng Xiang iD, Weilin Zeng, Yucheng Qin, Maohua Pan, Yanrui Wu iD, Mengxi Duan, Ye Mou, Tao Liang, Yanmei Zhang iD, Cheng Liu iD, Xiuya Tang, Yaming Huang iD, Gongchao Yang iD, Liwang Cui iD, Zhaoqing Yang iD

Abstract

Plasmodium falciparum acetyl-CoA synthetase (PfACAS) protein is an important source of acetyl-CoA. We detected the mutations S868G and V949I in PfACAS by whole-genome sequencing analysis in some recrudescent parasites after antimalarial treatment with artesunate and dihydroartemisinin-piperaquine, suggesting that they may confer drug resistance. Using CRISPR/Cas9 technology, we engineered parasite lines carrying the PfACAS S868G and V949I mutations in two genetic backgrounds and evaluated their susceptibility to antimalarial drugs in vitro. The results demonstrated that PfACAS S868G and V949I mutations alone or in combination were not enough to provide resistance to antimalarial drugs.

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