Superresolution imaging of antibiotic- induced structural disruption of bacteria enabled by photochromic glycomicelles

• 成果类型: Article
• 署名作者: Hu, Xi-Le; Gan, Hui-Qi; Gui, Wen-Zhen; Yan, Kai-Cheng; Sessler, Jonathan L.; Yi, Dong; Tian, He; He, Xiao-Peng
• 署名单位: East China University of Science & Technology; East China University of Science & Technology; Naval Medical University; University of Bath; University of Texas System; University of Texas Austin
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10439
• DOI: 10.1073/pnas.2408716121
• 发表日期: 2024-09-10
• 关键词: resistance; CHALLENGES; protein

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.