Distinct non-synonymous mutations in cytochrome b highly correlate with decoquinate resistance in apicomplexan parasite Eimeria tenella

文献类型： 外文期刊

第一作者： Hao, Zhenkai

作者： Hao, Zhenkai;Chen, Junmin;Sun, Pei;Chen, Linlin;Chen, Wenxuan;Bi, Feifei;Han, Zhenyan;Suo, Jingxia;Suo, Xun;Liu, Xianyong;Hao, Zhenkai;Chen, Junmin;Sun, Pei;Chen, Linlin;Chen, Wenxuan;Bi, Feifei;Han, Zhenyan;Suo, Jingxia;Suo, Xun;Liu, Xianyong;Zhang, Yuanyuan;Zhang, Yuanyuan;Hu, Dandan;Tang, Xinming

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关键词： Eimeria tenella; Drug resistance; Decoquinate; Whole-genome sequencing; Cytochrome b; Non-synonymous mutation

期刊名称：PARASITES & VECTORS （ 影响因子：3.2； 五年影响因子：3.6 ）

ISSN： 1756-3305

年卷期： 2023 年 16 卷 1 期

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收录情况： SCI

摘要： Background Protozoan parasites of the genus Eimeria are the causative agents of chicken coccidiosis. Parasite resistance to most anticoccidial drugs is one of the major challenges to controlling this disease. There is an urgent need for a molecular marker to monitor the emergence of resistance against anticoccidial drugs, such as decoquinate.Methods We developed decoquinate-resistant strains by successively exposing the Houghton (H) and Xinjiang (XJ) strains of E. tenella to incremental concentrations of this drug in chickens. Additionally, we isolated a decoquinate-resistant strain from the field. The resistance of these three strains was tested using the criteria of weight gain, relative oocyst production and reduction of lesion scores. Whole-genome sequencing was used to identify the non-synonymous mutations in coding genes that were highly associated with the decoquinate-resistant phenotype in the two laboratory-induced strains. Subsequently, we scrutinized the missense mutation in a field-resistant strain for verification. We also employed the AlphaFold and PyMOL systems to model the alterations in the binding affinity of the mutants toward the drug molecule.Results We obtained two decoquinate-resistant (DecR) strains, DecR_H and XJ, originating from the original H and XJ strains, respectively, as well as a decoquinate-resistant E. tenella strain from the field (DecR_SC). These three strains displayed resistance to 120 mg/kg decoquinate administered through feed. Through whole-genome sequencing analysis, we identified the cytochrome b gene (cyt b; ETH2_MIT00100) as the sole mutated gene shared between the DecR_H and XJ strains and also detected this gene in the DecR_SC strain. Distinct non-synonymous mutations, namely Gln131Lys in DecR_H, Phe263Leu in DecR_XJ, and Phe283Leu in DecR_SC were observed in the three resistant strains. Notably, these mutations were located in the extracellular segments of cyt b, in close proximity to the ubiquinol oxidation site Q(o). Drug molecular docking studies revealed that cyt b harboring these mutants exhibited varying degrees of reduced binding ability to decoquinate.Conclusions Our findings emphasize the critical role of cyt b mutations in the development of decoquinate resistance in E. tenella. The strong correlation observed between cyt b mutant alleles and resistance indicates their potential as valuable molecular markers for the rapid detection of decoquinate resistance.

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