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

Xi Le Hu; Hui Qi Gan; Wen Zhen Gui; Kai Cheng Yan; Jonathan L. Sessler; Dong Yi; He Tian; Xiao Peng He

doi:10.1073/pnas.2408716121

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

Xi Le Hu, Hui Qi Gan, Wen Zhen Gui, Kai Cheng Yan, Jonathan L. Sessler, Dong Yi, He Tian, Xiao Peng He

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e2408716121
Pages (from-to)	e2408716121
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	121
Issue number	37
Early online date	3 Sept 2024
DOIs	https://doi.org/10.1073/pnas.2408716121
Publication status	Published - 10 Sept 2024

Data Availability Statement

All study data are included in the article and/or SI Appendix.

Acknowledgements

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.

Funding

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*).

Funders	Funder number
Shanghai Advanced Research Institute
State Key Laboratory of Bioreactor Engineering
Chinese Academy of Sciences
Science and Technology Commission of Shanghai Municipality	2018SHZDZX03
National Natural Science Foundation of China	82130099, 92253306
State Key Laboratory of Drug Research, Chinese Academy of Sciences	SKLDR-2023-KF-10
Ministry of Education Key Laboratory on signaling Regulation and Targeting Therapy of Liver Cancer	2023-MEKLLC-MS/ZD-00*
Fundamental Research Funds for the Central Universities	222201717003
Project 211	B16017
Welch Foundation	F-0018
International Science and Technology Cooperation Program of Shanxi Province	23490711600

Keywords

antibiotics
fluorescence imaging
photochromism
superbugs
superresolution

ASJC Scopus subject areas

General

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10.1073/pnas.2408716121Licence: CC BY-NC-ND

Cite this

Hu, X. L., Gan, H. Q., Gui, W. Z., Yan, K. C., Sessler, J. L., Yi, D., Tian, H., & He, X. P. (2024). Superresolution imaging of antibiotic-induced structural disruption of bacteria enabled by photochromic glycomicelles. Proceedings of the National Academy of Sciences of the United States of America, 121(37), e2408716121. Article e2408716121. https://doi.org/10.1073/pnas.2408716121

Superresolution imaging of antibiotic-induced structural disruption of bacteria enabled by photochromic glycomicelles. / Hu, Xi Le; Gan, Hui Qi; Gui, Wen Zhen et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 121, No. 37, e2408716121, 10.09.2024, p. e2408716121.

Research output: Contribution to journal › Article › peer-review

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

Abstract

Data Availability Statement

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

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