Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo

Li, Ying1,2; Liu, Fei2; Zhang, Jiangjiang3; Liu, Xiaoye2; Xiao, Peihong1; Bai, Haotian4; Chen, Shang2; Wang, Dong1; Sung, Simon H. P.4; Kwok, Ryan T. K.4; Shen, Jianzhong2; Zhu, Kui2; Tang, Ben Zhong1,4

2021-03-01

10.1002/advs.202001750

ADVANCED SCIENCE   影响因子和分区

2198-3844

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 luminogen antibiotic autophagy internalized bacteria MRSA

SCI ; EI

英语

其他

National Key Research and Development Program of China[2017YFC1600305] ; Research Grants Council of Hong Kong[C6009-17G] ; Innovation and Technology Commission[ITC-CNERC14SC01] ; National Natural Science Foundation of China[31772796,22005195]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000623922000001

WILEY

20211010025323

Aniline ; Antibiotics ; Cell death

Medicine and Pharmacology:461.6 ; Biology:461.9 ; Organic Compounds:804.1

Web of Science

1.Shenzhen Univ, Coll Mat Sci & Engn, Ctr AIE Res, Shenzhen 518061, Peoples R China
2.China Agr Univ, Coll Vet Med, Natl Ctr Vet Drug Safety Evaluat, 2 Yuanmingyuan West Rd, Beijing 100193, Peoples R China
3.Southern Univ Sci & Technol, Dept Biomed Engn, 1088 Xueyuan Rd, Shenzhen 518055, Peoples R China
4.Hong Kong Univ Sci & Technol, Inst Adv Study, Div Life Sci,Dept Chem,Kowloon, Hong Kong Branch,Chinese Natl Engn Res Ctr Tissue, Clear Water Bay, Hong Kong, Peoples R China

Li, Ying,Liu, Fei,Zhang, Jiangjiang,et al. Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo[J]. ADVANCED SCIENCE,2021,8.

Li, Ying.,Liu, Fei.,Zhang, Jiangjiang.,Liu, Xiaoye.,Xiao, Peihong.,...&Tang, Ben Zhong.(2021).Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo.ADVANCED SCIENCE,8.

Li, Ying,et al."Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo".ADVANCED SCIENCE 8(2021).