A designed whole-cell biosensor for live diagnosis of gut inflammation through nitrate sensing = 질산염 감지를 통한 장내 염증을 진단할 수 있는 디자인 미생물 개발

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Title
A designed whole-cell biosensor for live diagnosis of gut inflammation through nitrate sensing = 질산염 감지를 통한 장내 염증을 진단할 수 있는 디자인 미생물 개발
Author(s)
Seung Gyun Woo; Sung-Je Moon; Seong Keun Kim; Tae Hyun Kim; Hyun Seung Lim; Gun Hwi Yeon; Bong Hyun SungChul Ho LeeSeung Goo LeeJung Hwan HwangDae-Hee Lee
Bibliographic Citation
Biosensors & Bioelectronics, vol. 168, pp. 112523-112523
Publication Year
2020
Abstract
Microbes reprogrammed using advanced genetic circuits are envisaged as emerging living diagnostics for a wide range of diseases and play key roles in regulating gut microbiota to treat disease-associated symptoms in a non-invasive manner. Here, we developed a designer probiotic Escherichia coli that senses and responds to nitrate, a biomarker of gut inflammation. To this end, we first employed the NarX-NarL two-component regulatory system in E. coli to construct a nitrate-responsive genetic circuit. Next, we optimized the nitrate biosensor for the best performance using measures of sensitivity and specificity. We then introduced this genetic circuit into a probiotic E. coli Nissle 1917. We demonstrated that the designed biosensor can sense elevated nitrate levels during gut inflammation in mice with native gut microbiota. Moreover, using Boolean AND gate, we generated a genetically encoded biosensor for simultaneous sensing of the thiosulfate and nitrate biomarkers, thus increasing the tool's specificity for diagnosing gut inflammation. The nitrate-responsive genetic circuit will enable new approaches for non-invasive diagnostics of inflammation-associated diseases.
Keyword
Whole cell biosensorGut inflammationDesigner probioticNitrate sensingThiosulfate sensingBoolean AND gate
ISSN
0956-5663
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bios.2020.112523
Type
Article
Appears in Collections:
Division of Biomaterials Research > Synthetic Biology and Bioengineering Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
Division of Biomaterials Research > 1. Journal Articles
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