In vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter

Qian Zhang, Bin Song, Yanan Xu, Yunmin Yang, Jian Ji, Wenjun Cao, Jianping Lu, Jiali Ding, Haiting Cao, Binbin Chu, Jiaxu Hong (), Houyu Wang () and Yao He ()
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Qian Zhang: Soochow University
Bin Song: Soochow University
Yanan Xu: Soochow University
Yunmin Yang: Soochow University
Jian Ji: Fudan University
Wenjun Cao: Fudan University
Jianping Lu: Soochow University
Jiali Ding: Soochow University
Haiting Cao: Soochow University
Binbin Chu: Soochow University
Jiaxu Hong: Fudan University
Houyu Wang: Soochow University
Yao He: Soochow University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Most existing bioluminescence imaging methods can only visualize the location of engineered bacteria in vivo, generally precluding the imaging of natural bacteria. Herein, we leverage bacteria-specific ATP-binding cassette sugar transporters to internalize luciferase and luciferin by hitchhiking them on the unique carbon source of bacteria. Typically, the synthesized bioluminescent probes are made of glucose polymer (GP), luciferase, Cy5 and ICG-modified silicon nanoparticles and their substrates are made of GP and D-luciferin-modified silicon nanoparticles. Compared with bacteria with mutations in transporters, which hardly internalize the probes in vitro (i.e., ~2% of uptake rate), various bacteria could robustly engulf the probes with a high uptake rate of around 50%. Notably, the developed strategy enables ex vivo bioluminescence imaging of human vitreous containing ten species of pathogens collected from patients with bacterial endophthalmitis. By using this platform, we further differentiate bacterial and non-bacterial nephritis and colitis in mice, while their chemiluminescent counterparts are unable to distinguish them.

Date: 2023
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DOI: 10.1038/s41467-023-37827-9

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