The mammalian microbiome plays a crucial role in maintaining health and preventing disease. Thanks to genetic engineering, non-invasive imaging of microorganisms within the mammalian host has become possible. However, these imaging methods are only applicable to engineered bacteria and cannot be used for natural bacteria. This is because commensal and pathogenic bacteria are difficult to genetically engineer. In order to address this limitation, a simpler approach is to selectively introduce luminescent reporters into bacterial cells for imaging purposes. However, this approach is technically challenging due to the formidable barrier presented by the bacterial cell wall.
In response to this challenge, the team of Prof. Yao He and Houyu Wang from the Institute of Functional Nano & Soft Material of Soochow University (FUNSOM) in collaboration with Prof. Jiaxu Hong, Director of the Dry Eye Center of the Fudan University Affiliated Eye and Ear Infection Hospital, recently published a paper on imaging and treatment of bacterial infections in a previous work (Adv. Mater. 2023, https://doi.org/). 10.1002/adma.20230047; Nat. Commun. 2022, 13, 5127; Nat. Commun. 2022, 13, 1255; Angew. Chem. Int. Ed. 2022, 61, e202208422; Nat. Commun. 2019, 10, 4057). ) basis, further using bacterial-specific ATP-binding cassette (ABC) sugar transporter proteins, luciferase, and luciferin were selectively internalized into various bacteria by coupling glucose polymers, a unique carbon source for bacteria. The constructed BLI probes can be internalized into Gram-positive and Gram-negative bacteria, in contrast to bacteria that cannot enter ABC protein mutations, such as deletion mutants of delta-lamB (ΔlamB) and delta-malE (ΔmalE), demonstrating that the constructed probes do enter bacteria via the ABC sugar transporter pathway. At the same time, the constructed BLI probes were hardly taken up by mammalian cells due to the absence of such transporter proteins in mammalian cells. On this basis, the developed probe was able to perform bioluminescence imaging of ten different bacterial pathogens extracted from the vitreous humor of patients with endophthalmitis. In addition, unlike conventional chemiluminescent probes (e.g., luminol) that cannot distinguish between bacterial and non-bacterial inflammation, the developed probe is capable of selective bioluminescence imaging of bacterial nephritis or colitis. The related results were published in the journal Nature Communication (Nat. Commun. 2023, 14, 2331). MS students Qian Zhang and Yanan Xu and assistant researcher Bin Song are co-first authors of the article.
Link：https://www.nature.com/articles/s41467-023-37827-9
Title：In vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter
Authors：Qian Zhang#, Bin Song#, Yanan Xu#, Yunmin Yang, Jian Ji, Wenjun Cao, Jianping Lu, Jiali Ding, Haiting Cao, Binbin Chu, Jiaxu Hong*, Houyu Wang* & Yao He*
Editor: Guo Jia