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

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.

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“…Gao et al [50] synthesized a DNA-mediated Au@Ag@silica nanofluorescent probe for high-performance NIR imaging of probiotics in vivo. Recently, Zhang et al [51] developed a Trojan-bioluminescent probe (Trojan-BLI), which combined luciferase and a substrate using glucose polymer-modified nanocarriers. The bacteria-specific ATP-binding cassette sugar transporter protein was utilized in that study to achieve natural bacterial uptake of the nanocarriers, thus enabling dynamic NIR imaging of bacteria in deep tissues.…”