Engineering bacterial thiosulfate and tetrathionate sensors for detecting gut inflammation

设计细菌硫代硫酸盐和四硫酸盐传感器用于检测肠道炎症

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作者:Kristina N-M Daeffler, Jeffrey D Galley, Ravi U Sheth, Laura C Ortiz-Velez, Christopher O Bibb, Noah F Shroyer, Robert A Britton, Jeffrey J Tabor

Abstract

There is a groundswell of interest in using genetically engineered sensor bacteria to study gut microbiota pathways, and diagnose or treat associated diseases. Here, we computationally identify the first biological thiosulfate sensor and an improved tetrathionate sensor, both two-component systems from marine Shewanella species, and validate them in laboratory Escherichia coli Then, we port these sensors into a gut-adapted probiotic E. coli strain, and develop a method based upon oral gavage and flow cytometry of colon and fecal samples to demonstrate that colon inflammation (colitis) activates the thiosulfate sensor in mice harboring native gut microbiota. Our thiosulfate sensor may have applications in bacterial diagnostics or therapeutics. Finally, our approach can be replicated for a wide range of bacterial sensors and should thus enable a new class of minimally invasive studies of gut microbiota pathways.

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