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Effective management of insecticide resistance requires identification of all toxicity\u2010affecting members from each family of toxicity\u2010related genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Here, we used emamectin benzoate (EB), ABC transporters and <jats:italic>Spodoptera frugiperda<\/jats:italic> as a working case to test whether the strategy of \u2018from the model insect <jats:italic>Drosophila melanogaster<\/jats:italic> to agricultural pests\u2019 can identify all or most ABC transporter members related to EB tolerance in <jats:italic>S. frugiperda<\/jats:italic>. After confirming the involvement of ABC transporters in the toxicity of EB against fruit fly with the ABC inhibitor verapamil, four ABC transporter genes (<jats:italic>DmCG3327<\/jats:italic>, <jats:italic>DmCG11147<\/jats:italic>, <jats:italic>DmCG4822<\/jats:italic>, and <jats:italic>DmCG7627<\/jats:italic>) were found to be involved in EB tolerance using RNA interference\u2010based family\u2010wide functional screening. A combination of phylogenic analysis and a reciprocal TBLASTN search identified five <jats:italic>S. frugiperda<\/jats:italic> ABC transporter members as homologs (<jats:italic>SfABCC4<\/jats:italic>, <jats:italic>SfABCG1<\/jats:italic>, and <jats:italic>SfABCG23<\/jats:italic>) or one\u2010way best hits (<jats:italic>SfABCG4<\/jats:italic> and <jats:italic>SfABCG20<\/jats:italic>) of the four fly ABC genes. Real\u2010time quantitative polymerase chain reaction (qPCR) analysis found that all five <jats:italic>S. frugiperda<\/jats:italic> ABC transporter genes were inducible by EB, and expressed in all the developmental stages and larval tissues, but with significant quantitative differences among stages and tissues. A cytotoxicity assay of ABC\u2010overexpressing <jats:italic>Sf9<\/jats:italic> cell lines showed that all the five <jats:italic>S. frugiperda<\/jats:italic> ABC transporter genes made <jats:italic>Sf9<\/jats:italic> cells tolerant to EB.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>This study not only identifies nine ABC transporter genes related to EB tolerance from <jats:italic>D. melanogaster<\/jats:italic> (four genes) and <jats:italic>S. frugiperda<\/jats:italic> (five genes), but also demonstrates the utility and effectiveness of the \u2018model to pests\u2019 strategy to identify most toxicity\u2010affecting members from a given family of toxicity\u2010related genes. \u00a9 2024 Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ps.8437","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T06:12:01Z","timestamp":1727331121000},"page":"340-350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Characterization of <scp>ATP<\/scp>\u2010binding cassette transporters associated with emamectin benzoate tolerance: from the model insect <i>Drosophila melanogaster<\/i> to the agricultural pest <i>Spodoptera frugiperda<\/i>"],"prefix":"10.1002","volume":"81","author":[{"given":"Lixiang","family":"Wang","sequence":"first","affiliation":[{"name":"Zhengzhou Research Base, State Key Laboratory of Cotton Biology, School of Agricultural Sciences Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyi","family":"Guo","sequence":"additional","affiliation":[{"name":"Zhengzhou Research Base, State Key Laboratory of Cotton 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