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At present, treatment of coccidiosis mainly relies on drugs. Anticoccidial drugs can be divided into two categories: ionophorous compounds and synthetic drugs. However, the emergence of drug\u2010resistant strains has become a challenge for coccidiosis control with anticoccidial drugs. To gain insights into the molecular mechanism governing the drug resistance of <jats:italic>Eimeria tenella<\/jats:italic>, two drug\u2010resistant strains of <jats:italic>E.\u00a0tenella<\/jats:italic>, one maduramicin\u2010resistant (<jats:styled-content style=\"fixed-case\">MRR<\/jats:styled-content>) strain and one diclazuril\u2010resistant (<jats:styled-content style=\"fixed-case\">DZR<\/jats:styled-content>) strain, were generated. We carried out comparative transcriptome analyses of a drug\u2010sensitive strain (<jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>) and two drug\u2010resistant <jats:styled-content style=\"fixed-case\">MRR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DZR<\/jats:styled-content> strains of <jats:italic>E.\u00a0tenella<\/jats:italic> using <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010sequencing. A total of 1,070 differentially expressed genes (<jats:styled-content style=\"fixed-case\">DEG<\/jats:styled-content>s), 672 upregulated and 398 downregulated, were identified in <jats:styled-content style=\"fixed-case\">MRR<\/jats:styled-content> vs. <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>, and 379 <jats:styled-content style=\"fixed-case\">DEG<\/jats:styled-content>s, 330 upregulated and 49 downregulated, were detected in <jats:styled-content style=\"fixed-case\">DZR<\/jats:styled-content> vs. <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to better understand the functions of these <jats:styled-content style=\"fixed-case\">DEG<\/jats:styled-content>s. In the comparison of <jats:styled-content style=\"fixed-case\">DZR<\/jats:styled-content> vs. <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>, some <jats:styled-content style=\"fixed-case\">DEG<\/jats:styled-content>s were involved in peroxisome, biosynthesis of unsaturated fatty acids, and fatty acid metabolism. In the comparison of <jats:styled-content style=\"fixed-case\">MRR<\/jats:styled-content> vs. <jats:styled-content style=\"fixed-case\">DS<\/jats:styled-content>, some <jats:styled-content style=\"fixed-case\">DEG<\/jats:styled-content>s were involved in glycolysis\/gluconeogenesis, regulation of actin cytoskeleton, and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> replication. In addition, some <jats:styled-content style=\"fixed-case\">DEG<\/jats:styled-content>s coded for surface antigens that were downregulated in two drug\u2010resistant strains involved invasion, pathogenesis, and host\u2013parasite interactions. These results provided suggestions for further research toward unraveling the molecular mechanisms of drug resistance in <jats:italic>Eimeria<\/jats:italic> species and contribute to developing rapid molecular methods to detect resistance to these drugs in <jats:italic>Eimeria<\/jats:italic> species in poultry.<\/jats:p>","DOI":"10.1111\/jeu.12790","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T13:57:09Z","timestamp":1580997429000},"page":"406-416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Comparative Transcriptome Analyses of Drug\u2010sensitive and Drug\u2010resistant Strains of <i>Eimeria tenella<\/i> by <scp>RNA<\/scp>\u2010sequencing"],"prefix":"10.1111","volume":"67","author":[{"given":"Yuxiang","family":"Xie","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences Minhang, Shanghai 200241 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences Minhang, Shanghai 200241 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology and Bovine Breeding Institute of Animal Science Chinese Academy of Agricultural Sciences Haidian District, Beijing 100193 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences Minhang, Shanghai 200241 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunhai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences Minhang, Shanghai 200241 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanzhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences Minhang, Shanghai 200241 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences Minhang, Shanghai 200241 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-6705","authenticated-orcid":false,"given":"Hongyu","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences Minhang, Shanghai 200241 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