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Despite ongoing efforts, currently available approaches remain restricted. Herein, a novel strategy involving the rational construction of an aggregation\u2010induced\u2010emission luminogen (AIEgen) is introduced to significantly enhance Gram\u2010positive bacteria's susceptibility to AGs. The application of this approach involves the simple addition of AIEgens to bacteria followed by a 5 min light irradiation. Under light exposure, AIEgens efficiently generate reactive oxygen species (ROS), elevating intrabacterial ROS levels to a nonlethal threshold. Post treatment, the bacteria swiftly enter a hypersensitive state, resulting in a 21.9\u2010fold, 15.5\u2010fold, or 7.2\u2010fold increase in susceptibility to three AGs: kanamycin, gentamycin, and neomycin, respectively. Remarkably, this approach is specific to AGs, and the induced hypersensitivity displays unparalleled longevity and heritability. Further in vivo studies confirm a 7.0\u2010fold enhanced bactericidal ability of AGs against Gram\u2010positive bacteria through this novel approach. This research not only broadens the potential applications of AIEgens but also introduces a novel avenue to bolster the effectiveness of AGs in combating bacterial infections.<\/jats:p>","DOI":"10.1002\/adhm.202400362","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T13:29:17Z","timestamp":1716211757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exciting Bacteria to a Hypersensitive State for Enhanced Aminoglycoside Therapy by a Rationally Constructed AIE Luminogen"],"prefix":"10.1002","volume":"13","author":[{"given":"Chao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology Key Laboratory for Tumor Precision Medicine of Shaanxi Province The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an 710061 P. R. 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