Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.
Angew Chem Int Ed Engl. 2020 Jun 8;59(24):9288-9292. doi: 10.1002/anie.201910187. Epub 2019 Sep 18.
Protected by the host cells, the hidden intracellular bacteria are typically difficult to kill by common antibiotics and cannot be visualized without complex cellular pretreatments. Herein, we successfully developed a bacteria-metabolizable dual-functional probe TPEPy-d-Ala, which is based on d-alanine and a photosensitizer with aggregation-induced emission for fluorescence turn-on imaging of intracellular bacteria in living host cells and photodynamic ablation in situ. Once metabolically incorporated into bacterial peptidoglycan, the intramolecular motions of TPEPy-d-Ala are inhibited, leading to an enhanced fluorescent signal, which allows the clear visualization of the intracellular bacteria. Moreover, TPEPy-d-Ala can effectively ablate the labeled intracellular bacteria in situ owing to covalent ligation to peptidoglycan, yielding a low intracellular minimum inhibitory concentration (MIC) of 20±0.5 μg mL , much more efficient than that of a commonly used antibiotic, vancomycin.
受宿主细胞的保护，隐藏在细胞内的细菌通常很难被普通抗生素杀死，并且如果没有复杂的细胞预处理，就无法观察到。在此，我们成功开发了一种细菌可代谢的双重功能探针 TPEPy-d-Ala，它基于 d-丙氨酸和一种具有聚集诱导发射的光致剂，用于活宿主细胞内的细胞内细菌的荧光开启成像和原位光动力消融。一旦被代谢纳入细菌肽聚糖中，TPEPy-d-Ala 的分子内运动就会受到抑制，导致荧光信号增强，从而可以清晰地观察到细胞内的细菌。此外，由于与肽聚糖的共价连接，TPEPy-d-Ala 可以有效地原位消融标记的细胞内细菌，其细胞内最低抑菌浓度 (MIC) 低至 20±0.5μg/mL，比常用抗生素万古霉素的效率高得多。
