The F204S mutation in adrenodoxin oxidoreductase drives salinomycin resistance in Eimeria tenella.

Salinomycin is a polyether ionophore widely used for the treatment of coccidiosis in poultry. However, the emergence of coccidia strains resistant to salinomycin presents challenges for control efforts, and the mechanisms underlying this resistance in Eimeria remain inadequately understood. In this study, 78 stable salinomycin-resistant strains were generated through experimental evolution approaches. Whole-genome sequencing of salinomycin-resistant Eimeria tenella isolates revealed single nucleotide polymorphisms (SNPs), with 12 candidate genes harboring nonsynonymous mutations identified. To confirm the candidate gene responsible for conferring salinomycin resistance, we leveraged reverse genetic strategies and identified a key amino acid substitution (F204S) in adrenodoxin oxidoreductase (EtADR), which markedly reduced susceptibility to salinomycin. Our results elucidate the complex interactions among salinomycin resistance, parasite fitness, point mutations, and the structure of EtADR, laying the foundation for future studies on drug resistance in Eimeria and contributing to the development of targeted control strategies.
Competing Interests: Declarations. Ethics approval and consent to participate: All chickens in our study were subjected to experiments in accordance with the China Agricultural University Institutional Animal Welfare and Animal Experimental Ethical Inspection (Approval number: AW22022202-1-1). Competing interests: The authors declare that they have no competing interests.
(© 2024. The Author(s).)