文献类型：期刊文献

英文题名：Superresolution imaging of antibiotic- induced structural disruption of bacteria enabled by photochromic glycomicelles

作者：Hu, Xi-Le[1,2];Gan, Hui-Qi[1,2];Gui, Wen-Zhen[1,2];Yan, Kai-Cheng[2,3,4];Sessler, Jonathan L.[5];Yi, Dong[6];Tian, He[1,2];He, Xiao-Peng[1,2,3]

机构：[1]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Sch Chem & Mol Engn, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Sch Chem & Mol Engn, Joint Int Res Lab Precis Chem & Mol Engn, Shanghai 200237, Peoples R China;[3]Eastern Hepatobiliary Surg Hosp, Natl Ctr Liver Canc, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China;[4]Univ Bath, Dept Chem, Bath BA2 7AY, England;[5]Univ Texas Austin, Dept Chem, Austin, TX 78712 USA;[6]China State Inst Pharmaceut Ind, Res Ctr Syst Biosynth, Natl Key Lab Lead Druggabil Res, Shanghai 201203, Peoples R China

年份：2024

卷号：121

期号：37

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001347914100006)】；

基金：This work was financially supported by the National Natural Science Foundation of China (Nos. 92253306 and 82130099) , the Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX03) , the International Cooperation Program of Shanghai Science and Technology (No. 23490711600) , the Fundamental Research Funds for the Central Universities (222201717003) , the Programme of Introducing Talents of Discipline to Universities (B16017) , and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering, the State Key Laboratory of Drug Research (SKLDR-2023-KF-10) and the Ministry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer (Grant. 2023-MEKLLC-MS/ZD-00*) . Support from the Robert A. Welch Foundation (F-0018 to J.L.S.) is also acknowledged. The Research Center of Analysis and Test of East China University of Science and Technology is gratefully acknowledged for assistance in analytical experiments. We thank Ren-Yu Yang for his partial contribution to the synthesis of the probes and Yao Li and other staff members of the Integrated Laser Microscopy System at the National Facility for Prote in Science in Shanghai (NFPS) ,Shanghai Advanced Research Institute, Chinese Academy of Science, China for sample preparation, data collection, and analysis.

语种：英文

外文关键词：superresolution; fluorescence imaging; antibiotics; superbugs; photochromism

摘要：Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic- induced structural disruption of bacteria. Conjugation between a spiropyran (SP) and galactose via click chemistry produces an amphiphilic photochromic glycoprobe, which self- assembles into glycomicelles in water. The hydrophobic inner core of the glycomicelles allows encapsulation of antibiotics. Photoirradiation then serves to convert the SP to the corresponding merocyanine (MR) form. This results in micellar disassembly allowing for release of the antibiotic in an on- demand fashion. The glycomicelles of this study adhere selectively to the surface of a Gram- negative bacterium through multivalent sugar-lectin interaction. Antibiotic release from the glycomicelles then induces membrane collapse. This dynamic process can be imaged in situ by superresolution spectroscopy owing to the "fluorescence blinking" of the SP/MR photochromic pair. This research provides a high- precision imaging tool that may be used to visualize how antibiotics disrupt the structural integrity of bacteria in real time.