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

iScience · 13 authors, 6 centres

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TL;DR

A strong selective sweep at the EtcPRS (ETH2_1020900) locus was detected, narrowing resistance-associated changes to two mutations including an amino acid substitution T618A.

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A strong selective sweep at the EtcPRS (ETH2_1020900) locus was detected, narrowing resistance-associated changes to two mutations including an amino acid substitution T618A. Reverse genetic engineering of these mutations into wild-type E. tenella confirmed they confer halofuginone resistance. Limitations include reliance on laboratory-induced rather than field-resistant strains, absence of conditional knockout approaches in E. tenella, and lack of a successive in vitro culture system for coccidia.

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other

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preclinical research

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ORIGINAL PAPER

PMC10031133

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

iScience

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ABSTRACT

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. Subject areas: Molecular biology, Parasitology, Medical microbiology

CITATION EXPORT

Pei Sun, Yuanyuan Zhang, Chaoyue Wang et al.. EtcPRSMut as a molecular marker of halofuginone resistance in Eimeria tenella and Toxoplasma gondii. iScience. (2023). https://doi.org/10.1016/j.isci.2023.106334

AUTHORS

13 · 6 CENTRES

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

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