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Efficient Killing of Multidrug‐Resistant Internalized Bacteria by AIEgens In Vivo
Advanced Science ( IF 14.3 ) Pub Date : 2021-03-02 , DOI: 10.1002/advs.202001750 Ying Li 1, 2 , Fei Liu 2 , Jiangjiang Zhang 3 , Xiaoye Liu 2 , Peihong Xiao 1 , Haotian Bai 4 , Shang Chen 2 , Dong Wang 1 , Simon H P Sung 4 , Ryan T K Kwok 4 , Jianzhong Shen 2 , Kui Zhu 2 , Ben Zhong Tang 1, 4
Advanced Science ( IF 14.3 ) Pub Date : 2021-03-02 , DOI: 10.1002/advs.202001750 Ying Li 1, 2 , Fei Liu 2 , Jiangjiang Zhang 3 , Xiaoye Liu 2 , Peihong Xiao 1 , Haotian Bai 4 , Shang Chen 2 , Dong Wang 1 , Simon H P Sung 4 , Ryan T K Kwok 4 , Jianzhong Shen 2 , Kui Zhu 2 , Ben Zhong Tang 1, 4
Affiliation
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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 N,N‐diphenyl‐4‐(7‐(pyridin‐4‐yl) benzo [c] [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 Staphylococcus aureus (MRSA) in vivo. The studies suggest that AIEgens are promising new agents for the treatment of MDR bacteria associated infections.
中文翻译：
AIEgens 在体内有效杀死多重耐药内化细菌
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，而且还增加了病原体从最初感染部位的传播。抗生素很难且不足以治疗这些隐藏的内化细菌，尤其是多重耐药（MDR）细菌。在此，聚集诱导发射发光体（AIEgens），例如N，N-二苯基-4-（7-（吡啶-4-基）苯并[ c ][1,2,5]噻二唑-4-基）苯胺，用1-溴乙烷 (TBP-1) 和 (3-溴丙基) 三甲基溴化铵 (TBP-2) (TBP) 对细胞外和内化的革兰氏阳性病原体均表现出有效的广谱杀菌活性。无论光照射如何，TBP 都会触发活性氧 (ROS) 介导的膜损伤来杀死细菌。TBP 可有效杀死细菌而不产生耐药性。此外，此类 AIEgen 会激活线粒体依赖性自噬，以消除宿主细胞中内化的细菌。与临床常规使用的万古霉素相比，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 MDR 细菌相关感染的有前途的新药。
更新日期：2021-05-05
中文翻译：
AIEgens 在体内有效杀死多重耐药内化细菌
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，而且还增加了病原体从最初感染部位的传播。抗生素很难且不足以治疗这些隐藏的内化细菌，尤其是多重耐药（MDR）细菌。在此，聚集诱导发射发光体（AIEgens），例如N，N-二苯基-4-（7-（吡啶-4-基）苯并[ c ][1,2,5]噻二唑-4-基）苯胺，用1-溴乙烷 (TBP-1) 和 (3-溴丙基) 三甲基溴化铵 (TBP-2) (TBP) 对细胞外和内化的革兰氏阳性病原体均表现出有效的广谱杀菌活性。无论光照射如何，TBP 都会触发活性氧 (ROS) 介导的膜损伤来杀死细菌。TBP 可有效杀死细菌而不产生耐药性。此外，此类 AIEgen 会激活线粒体依赖性自噬，以消除宿主细胞中内化的细菌。与临床常规使用的万古霉素相比，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 MDR 细菌相关感染的有前途的新药。
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