EtcPRS Mut 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

doi:10.1016/j.isci.2023.106334

EtcPRS ^Mut as a molecular marker of halofuginone resistance in Eimeria tenella and Toxoplasma gondii

iScience. 2023 Mar 4;26(4):106334. doi: 10.1016/j.isci.2023.106334. eCollection 2023 Apr 21.

Authors

Pei Sun¹, Yuanyuan Zhang², Chaoyue Wang³, Dandan Hu⁴, Jie Liu¹, Linlin Chen¹, Fangyun Shi¹, Xinming Tang⁵, Zhenkai Hao¹, Jingxia Suo¹, Yonglan Yu⁶, Xun Suo¹, Xianyong Liu¹

Affiliations

¹ National Key Laboratory of Veterinary Public Health Security, Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, National Animal Protozoa Laboratory & College of Veterinary Medicine, China Agricultural University, Beijing, China.
² Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture & Beijing Key Laboratory of Animal Genetic Improvement, China Agricultural University, Beijing, China.
³ Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
⁴ School of Animal Science and Technology, Guangxi University, Nanning, China.
⁵ Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
⁶ Department of Clinic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Abstract

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.

Keywords: Medical microbiology; Molecular biology; Parasitology.