이대희 (한국생명공학연구원, UST) | 한빛사논문 > 한빛사

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한국생명공학연구원, UST

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Biosens. Bioelectron., Available online 20 August 2020, 112523 | https://doi.org/10.1016/j.bios.2020.112523 A designed whole-cell biosensor for live diagnosis of gut inflammation through nitrate sensing

Seung-Gyun Woo^a,b, Sung-Je Moon^b,c, Seong Keun Kim^a, Tae Hyun Kim^a,b, Hyun Seung Lim^a, Gun-Hwi Yeon^a,b, Bong Hyun Sung^a,b, Chul-Ho Lee^b,c, Seung-Goo Lee^a,b,*, Jung Hwan Hwang^b,c,*, Dae-Hee Lee^a,b,*

^aSynthetic Biology and Bioengineering Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea
^bDepartment of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, Republic of Korea
^cLaboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea

^*Corresponding author

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.

Keywords : Whole cell biosensor; Gut inflammation; Designer probiotic; Nitrate sensing; Thiosulfate sensing; Boolean AND gate

논문정보

형식Research article
게재일2020년 08월 (BRIC 등록일 2020-08-26)
연구진국내 연구진
분야 생명과학 > 생물공학

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