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Both have evolved practical resistance to transgenic crops producing <jats:italic>Bacillus thuringiensis<\/jats:italic> (<jats:italic>Bt<\/jats:italic>) toxins in the United States. GS\u2010omega\/kappa\u2010Hxtx\u2010Hv1a (\u03c9\/\u03ba\u2010Hv1a) is a novel biopesticide derived from spider venom with activity against lepidopteran pests. The efficacy of \u03c9\/\u03ba\u2010Hv1a is dependent on combining it with a facilitator product such as a <jats:italic>Bt<\/jats:italic>\u2010based insecticide. However, it is unknown if \u03c9\/\u03ba\u2010Hv1a can be an alternative for the management of <jats:italic>Bt<\/jats:italic> resistance. In this study, we tested the effect of \u03c9\/\u03ba\u2010Hv1a alone or in the presence of <jats:italic>Bt<\/jats:italic> toxins against susceptible and resistant <jats:italic>H. zea<\/jats:italic> and <jats:italic>S. frugiperda.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Diet overlays with 5\u2009\u03bcg\u2009cm<jats:sup>\u22122<\/jats:sup> of Vip3Aa39 significantly increased mortality in susceptible <jats:italic>H. zea<\/jats:italic> but did not enhance the activity of \u03c9\/\u03ba\u2010Hv1a against Vip3A\u2010resistant <jats:italic>H. zea<\/jats:italic>. In contrast, the addition of 10\u2009\u03bcg\u2009cm<jats:sup>\u22122<\/jats:sup> of Cry1Ac to the surface of \u03c9\/\u03ba\u2010Hv1a incorporated diet significantly increased the mortality of Cry\u2010resistant <jats:italic>H. zea<\/jats:italic> compared to diets without the Cry1Ac toxin.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The study confirms that \u03c9\/\u03ba\u2010Hv1a activity against <jats:italic>H. zea<\/jats:italic> is significantly enhanced by a facilitator mechanism. Our results suggest Cry1Ac pore formation in the midgut membrane of Cry\u2010resistant <jats:italic>H. zea<\/jats:italic>, enables the activity of \u03c9\/\u03ba\u2010Hv1a. Vip3Aa resistance in <jats:italic>H. zea<\/jats:italic> involves altered toxin\u2010binding, consequently preventing pore formation and activity of \u03c9\/\u03ba\u2010Hv1a. Therefore, insecticides containing \u03c9\/\u03ba\u2010Hv1a may be an alternative for managing Cry\u2010resistant <jats:italic>H. zea<\/jats:italic> in cotton and help delay the evolution of insect resistance. \u00a9 2025 The Author(s). <jats:italic>Pest Management Science<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ps.8725","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T07:25:17Z","timestamp":1739863517000},"page":"3565-3572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of <scp>GS<\/scp>\u2010omega\/kappa\u2010Hxtx\u2010Hv1a and <scp><i>Bt<\/i><\/scp> toxins against <scp><i>Bt<\/i>\u2010resistant<\/scp> and \u2010susceptible strains of <scp><i>Helicoverpa zea<\/i><\/scp> (Boddie) and <scp><i>Spodoptera frugiperda<\/i><\/scp> (J.E. Smith)"],"prefix":"10.1002","volume":"81","author":[{"given":"Simeon","family":"Ross","sequence":"first","affiliation":[{"name":"Department of Entomology Texas A&amp;M University  College Station TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Entomology University of Minnesota  St Paul MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 C.","family":"Santiago\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Entomology, Texas A&amp;M AgriLife Research and Extension at Amarillo  Amarillo USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Abdelgaffar","sequence":"additional","affiliation":[{"name":"Department of Entomology and Plant Pathology University of Tennessee  Knoxville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawson D.","family":"Kerns","sequence":"additional","affiliation":[{"name":"Department of Entomology and Plant Pathology University of Tennessee  Knoxville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8945-1814","authenticated-orcid":false,"given":"Juan Luis","family":"Jurat\u2010Fuentes","sequence":"additional","affiliation":[{"name":"Department of Entomology and Plant Pathology University of Tennessee  Knoxville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocun","family":"Sun","sequence":"additional","affiliation":[{"name":"Research Computing Support, Office of Information Technology University of Tennessee  Knoxville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayna","family":"Collett","sequence":"additional","affiliation":[{"name":"Vestaron Crop Protection  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Kerns","sequence":"additional","affiliation":[{"name":"Department of Entomology Texas A&amp;M University  College Station TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-ento-120220-105502"},{"key":"e_1_2_7_3_1","unstructured":"USDA Economic Research Service (ERS) Adoption of genetically gngineered crops in the U.S(2023). 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