From <i>De Novo</i> ‐Engineered Amphiphilic Molecules to Multifunctional Supramolecular Micelles: Enhanced Foliar Affinity, Potent Biofilm Disruption, and Effective Control of Bacterial Plant Diseases

Abstract Bacterial pathogens pose a serious threat to global agriculture, driven largely by the resilience of biofilms and the poor foliar affinity of conventional pesticides. Herein, a pharmacophore‐guided approach is presented for engineering amphiphilic molecules that integrate hydrophobic α ‐aminophosphonate and hydrophilic isopropanolamine moieties. Several amphiphiles self‐assemble into micelles whose stability and dispersibility are strengthened by 0.1% polyoxyethylene (20) sorbitan monolaurate (Tween 20), obviating the need for additional adjuvants. These supramolecular micelles, stabilized with 0.1% Tween 20, exhibit enhanced deposition and retention on plant leaves. At 200 µ g mL −1 , they conferred protective efficacy against bacterial leaf blight, streak, kiwifruit canker, or citrus canker, with rates of 41.61%–58.39%, consistently outperforming conventional agent thiodiazole‐copper (TC). Among them, F 35 @Tween 20 stands out for its superior foliar affinity, potency, environmental compatibility, stability, and rainfastness. Further investigations revealed its dual capacity to inhibit biofilm formation and eradicate mature biofilms. Mechanistic studies revealed that biofilm disruption coincides with reduced extracellular polysaccharide production and downregulation of biofilm‐associated virulence genes. With its defined mode of action, potent bioactivity, and favorable physicochemical and safety profiles, F 35 @Tween 20 emerges as a promising candidate for sustainable management of recalcitrant bacterial infections in agriculture.