iScience (Apr 2023)

EtcPRSMut as a molecular marker of halofuginone resistance in Eimeria tenella and Toxoplasma gondii

  • Pei Sun,
  • Yuanyuan Zhang,
  • Chaoyue Wang,
  • Dandan Hu,
  • Jie Liu,
  • Linlin Chen,
  • Fangyun Shi,
  • Xinming Tang,
  • Zhenkai Hao,
  • Jingxia Suo,
  • Yonglan Yu,
  • Xun Suo,
  • Xianyong Liu

Journal volume & issue
Vol. 26, no. 4
p. 106334

Abstract

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Summary: The control of coccidiosis, causing huge economic losses in the poultry industry, is facing the stagnation of the development of new drugs and the emergence of drug resistance. Thus, the priority for coccidiosis control is to decipher the effect mechanisms and resistance mechanisms of anticoccidial drugs. In this study, we mined and validated a molecular marker for halofuginone resistance in Eimeria tenella through forward and reverse genetic approaches. We screened whole-genome sequencing data and detected point mutations in the ETH2_1020900 gene (encoding prolyl-tRNA synthetase, PRS). Then, we introduced this mutated gene into E. tenella and Toxoplasma gondii and validated that overexpression of this mutated gene confers resistance to halofuginone in vivo and in vitro. These results together show that mutations A1852G and A1854G on the ETH2_1020900 gene are pivotal to halofuginone resistance in E. tenella, encouraging the exploration of mechanisms of drug resistance against other anticoccidial drugs in eimerian parasites.

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