An Efficient Probe for Bacterial Nitroreductase Imaging and Detection Based on NanoLuc‐Furimazine Bioluminescent Pair

Author:

Shi Ximeng1,Wang Yumeng2,Yu Jiaoyang34,Yang Yating5,Jin Zecheng1,Wang Hanghang1,Wu Dalei5,Chen Wei3,Guo Jianming2,Zhang Yinan1

Affiliation:

1. Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine Nanjing Jiangsu 210023 China

2. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Pharmacy, Nanjing University of Chinese Medicine Nanjing Jiangsu 210023 China

3. Clinical Research Center, the Second Hospital of Nanjing, Affiliated Hospital to Nanjing University of Chinese Medicine Nanjing Jiangsu 210003 China

4. Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University Xi’an Shaanxi 710069 China

5. Helmholtz International Lab, State Key Laboratory of Microbial Technology, Shandong University Qingdao Shandong 266237 China

Abstract

Comprehensive SummaryThe detection of critical endogenous species, such as bacteria in microenvironments in the body, requires better imaging tools for visualization and monitoring of biological events. Bioluminescence imaging is the most popular strategy for obtaining real‐time in living cells and organisms. Herein, we introduced a nitroaryl group on the C‐3 position and a hydroxy group at the C‐6 phenyl ring on furimazine to report the first bioluminescent probe (7) based on NanoLuc‐furimazine bioluminescent pair for the detection of nitroreductase in bacteria. The probe, which possessed up to 560‐fold intensity increase with a low detection limit of 16 ng/mL of nitroreductase, has the most efficient uncage efficiency in comparison with other bioluminescent congeners, thus enabling highly selective and sensitive visualization of NTR activity in a panel of clinical priority pathogens. Additionally, imaging of the recombinant strain as well as the NTR from mouse feces indicated the potential of this probe in the application of different mouse disease models.

Publisher

Wiley

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