Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo.
Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo.
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AIEgens 在体内有效杀灭多重耐药内化细菌
DOI：
10.1002/advs.202001750
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Tang BZ
中科院分区：
文献类型：
--
作者：
Li Y;Liu F;Zhang J;Liu X;Xiao P;Bai H;Chen S;Wang D;Sung SHP;Kwok RTK;Shen J;Zhu K;Tang BZ
被细菌感染的细胞扮演着“特洛伊木马”的角色，不仅保护细菌免受抗生素治疗和免疫清除的侵袭，还会增加病原体从最初感染部位的传播。抗生素很难治疗这种隐藏的内化细菌，特别是多药耐药(MDR)细菌。其中，用1-溴乙烷(TBP-1)和(3-溴丙基)三甲基溴化铵(TBP-2)官能化的N，N-二苯基-4-(7-(吡啶-4-基)苯并[c][1，2，5]噻二唑-4-基)苯胺(TBP-1和TBP-2)(TBP-2)等聚集型发光材料对细胞外和革兰氏阳性菌均显示出很强的广谱杀菌活性。Tbps触发活性氧物种(ROS)介导的膜损伤以杀死细菌，而不受光照射的影响。Tbps有效地杀灭细菌，而不产生抗药性。此外，这些AIEgen激活线粒体依赖的自噬，以消除宿主细胞中内化的细菌。与临床上常规使用的万古霉素相比，TBP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，AIEgen是治疗耐多药细菌相关性感染的有前途的新药物。聚集诱导发射发光物质(AIEgen)为追踪和剖析其在细菌中的作用模式和在宿主中的药代动力学过程提供了巨大的潜力。AIEgen作为一类新型的抗生素，通过触发活性氧(ROS)介导的膜损伤和激活线粒体依赖的自噬来杀灭细菌，有望促进哺乳动物细胞的细菌清除和治疗MRSA相关性腹膜炎。
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. Aggregation‐induced emission luminogens (AIEgens) offer great potentials to track and dissect their modes of action in bacteria and pharmacokinetics processes in hosts. AIEgens serve as a novel class of antibiotics by triggering reactive oxygen species (ROS)‐mediated membrane damage and by activating mitochondria dependent autophagy to kill bacteria, which are promising adjuvants to boost mammalian cells for bacterial clearance and treatment of MRSA associated peritonitis.
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影响因子：
11.3
作者：
Heeb S;Fletcher MP;Chhabra SR;Diggle SP;Williams P;Cámara M
通讯作者：
Cámara M
影响因子：
64.5
作者：
Kohanski, Michael A.;Dwyer, Daniel J.;Collins, James J.
通讯作者：
Collins, James J.
DOI：
10.1038/nrd.2017.162
发表时间：
2018-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
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通讯作者：
Bartenschlager R
影响因子：
12.4
作者：
Shi, Xiujuan;Sung, Simon H. P.;Tang, Ben Zhong
通讯作者：
Tang, Ben Zhong
影响因子：
3.6
作者：
Garner, WL
通讯作者：
Garner, WL