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The lipopeptides (LPs) iturin and fengycin derived from <jats:italic>Bacillus amyloliquefaciens<\/jats:italic> S76\u20103 exhibit highly inhibitory effects against pathogenic fungi, especially <jats:italic>Fusarium graminearum<\/jats:italic> (<jats:italic>Fg<\/jats:italic>), the primary pathogen causing <jats:italic>Fusarium<\/jats:italic> head blight (FHB) in cereals. However, the specific target of iturin and fengycin in <jats:italic>Fg<\/jats:italic> and the underlying mechanism of antagonistic activity remain unclear. Here, global transcriptome sequencing, combined with both genetic and chemical approaches, demonstrates that the LPs exhibit antagonism toward <jats:italic>Fg<\/jats:italic> by binding to multiple components in the cell membrane of <jats:italic>Fg<\/jats:italic> cells, including ergosterol, phospholipids, glycosylphosphatidylinositol, and ankyrin. Lipopeptides result in cell swelling by inducing cell wall remodeling and osmotic substance glycerol synthesis mediated by cell wall integrity and high\u2010osmolarity glycerol signaling pathways. Furthermore, we found that LPs can activate the induced systemic resistance in wheat against FHB and deoxynivalenol accumulation. Additionally, LPs were able to promote wheat growth by regulating auxin, cytokinin, and gibberellin signaling pathways while also delaying seed germination through the stimulation of abscisic acid and ethylene signaling pathways. These findings advance knowledge on the underlying mechanism of iturin and fengycin antagonistic activity and provide a new avenue for developing agricultural and clinical broad\u2010spectrum antifungal agents and identifying plant growth regulators in the future.<\/jats:p>","DOI":"10.1111\/jipb.13933","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T07:29:33Z","timestamp":1747812573000},"page":"2184-2197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Iturin and fengycin lipopeptides inhibit pathogenic <i>Fusarium<\/i> by targeting multiple components of the cell membrane and their regulative effects in wheat"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9713-099X","authenticated-orcid":false,"given":"Qing\u2010Song","family":"Yuan","sequence":"first","affiliation":[{"name":"College of Plant Science and Technology Huazhong Agricultural University Wuhan 430070 China"},{"name":"Resource Institute for Chinese &amp; Ethnic Materia Medica Guizhou University of Traditional Chinese Medicine Guiyang 550025 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3936-8844","authenticated-orcid":false,"given":"Peng","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Plant Science and Technology Huazhong Agricultural University Wuhan 430070 China"},{"name":"Jiangsu Ruihua Agricultural Science and Technology Co. 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