Center for AIE Research College of Materials Science and Engineering Shenzhen University Shenzhen 518061 China.
National Center for Veterinary Drug Safety Evaluation College of Veterinary Medicine China Agricultural University No. 2 Yuanmingyuan West Rd Beijing 100193 China.
Adv Sci (Weinh). 2021 Mar 2;8(9):2001750. doi: 10.1002/advs.202001750. eCollection 2021 May.
Bacteria infected cells acting as "Trojan horses" not only protect bacteria from antibiotic therapies and immune clearance, but also increase the dissemination of pathogens from the initial sites of infection. Antibiotics are hard and insufficient to treat such hidden internalized bacteria, especially multidrug-resistant (MDR) bacteria. Herein, aggregation-induced emission luminogens (AIEgens) such as ,-diphenyl-4-(7-(pyridin-4-yl) benzo [] [1,2,5] thiadiazol-4-yl) aniline functionalized with 1-bromoethane (TBP-1) and (3-bromopropyl) trimethylammonium bromide (TBP-2) (TBPs) show potent broad-spectrum bactericidal activity against both extracellular and internalized Gram-positive pathogens. TBPs trigger reactive oxygen species (ROS)-mediated membrane damage to kill bacteria, regardless of light irradiation. TBPs effectively kill bacteria without the development of resistance. Additionally, such AIEgens activate mitochondria dependent autophagy to eliminate internalized bacteria in host cells. Compared to the routinely used vancomycin in clinic, TBPs demonstrate comparable efficacy against methicillin-resistant (MRSA) in vivo. The studies suggest that AIEgens are promising new agents for the treatment of MDR bacteria associated infections.
细菌感染的细胞充当“特洛伊木马”，不仅保护细菌免受抗生素治疗和免疫清除，还增加了病原体从初始感染部位的传播。抗生素很难有效治疗这种隐藏的内化细菌，尤其是多药耐药 (MDR) 细菌。在此，用 1-溴乙烷（TBP-1）和（3-溴丙基）三甲基氯化铵（TBP-2）（TBPs）功能化的聚集诱导发射发光体（AIEgens），如 ，-二苯基-4-（7-（吡啶-4-基）苯并 [] [1,2,5]噻二唑-4-基）苯胺，显示出针对革兰氏阳性病原体的强大的广谱杀菌活性，无论是在细胞外还是内化的。TBPs 触发活性氧 (ROS) 介导的膜损伤来杀死细菌，而无需光照。TBPs 有效地杀死细菌而不会产生耐药性。此外，这种 AIEgens 激活线粒体依赖性自噬来消除宿主细胞中的内化细菌。与临床上常用的万古霉素相比，TBPs 在体内对耐甲氧西林金黄色葡萄球菌 (MRSA) 具有相当的疗效。研究表明，AIEgens 是治疗与 MDR 细菌相关感染的有前途的新型药物。
