文献类型：期刊文献

英文题名：Highly Sensitive In Vivo Imaging of Bacterial Infections with a Hydrophilicity-Switching, Self-Immobilizing, Near-Infrared Fluorogenic β-Lactamase Probe Enriched within Bacteria

作者：Chen, Fangfang[1];Li, Yuyao[1];Peng, Yan[1];Zhu, Yifan[1];He, Gao[1];Zhang, Zhengwei[2,3];Xie, Hexin[1]

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Pharm, State Key Lab Bioreactor Engn,Shanghai Frontier Sc, Shanghai 200237, Peoples R China;[2]Fudan Univ, Dept Nucl Med, Shanghai 200235, Peoples R China;[3]Fudan Univ, Huashan Hosp, PET Ctr, Shanghai 200235, Peoples R China

年份：2025

卷号：12

期号：5

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20245017527216);WOS:【SCI-EXPANDED(收录号:WOS:001375003000001)】；

基金：The authors greatly appreciate financial support from the NSFC (22077031 and 22207035), Fundamental Research Funds for the Central Universities, Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, grant 2021 Sci & Tech 03-28), and China Postdoctoral Science Foundation (2022M711149).

语种：英文

外文关键词：beta-lactamases; antibiotic resistance; bacterial infections; fluorescence probes; in vivo imaging

摘要：The emergence of antibiotic resistance, particularly bacterial resistance to beta-lactam antibiotics, the most widely prescribed therapeutic agents for infectious diseases, poses a significant threat to public health worldwide. The discovery of effective therapies against antibiotic-resistant pathogens has become an urgent need, necessitating innovative approaches to accelerate the identification and development of novel antibacterial agents. On the other hand, the expression of the beta-lactam-hydrolyzing enzyme (beta-lactamase), the major cause of bacterial resistance to beta-lactam antibiotics, provides a distinctive opportunity to visualize bacterial infection, evaluate the efficacy of existing antibiotics, screen for novel antibacterial agents, and optimize drug dosing regimens in live animals. Herein, a hydrophilicity-switching, self-immobilizing, near-Infrared fluorogenic beta-lactamase probe for the highly sensitive imaging of bacterial infection in live mice is reported. This probe, in addition to a significant increase in fluorescence upon selective hydrolysis by beta-lactamases as conventional beta-lactamase probes, also massively enriches within beta-lactamase-expressing bacteria (over 1500-folds compared to the incubation medium), which renders excellent sensitivity in the imaging of bacterial infections in living animals. This agent has proven to enable the assessment of antibiotic therapeutic efficacy and potency of beta-lactamase inhibitors in living animals in a non-invasive and much more convenient manner.