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Long-term monitoring of inflammation in the mammalian gut using programmable commensal bacteria

David T Riglar, Michael Baym, S Jordan Kerns, Matthew J Niederhuber, Roderick T Bronson, Jonathan W Kotula, Georg K Gerber, Jeffrey C Way, Pamela A Silver
doi: https://doi.org/10.1101/075051
David T Riglar
1Department of Systems Biology, Harvard Medical School, Boston MA 02115
2Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston MA 02115
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Michael Baym
1Department of Systems Biology, Harvard Medical School, Boston MA 02115
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S Jordan Kerns
1Department of Systems Biology, Harvard Medical School, Boston MA 02115
2Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston MA 02115
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Matthew J Niederhuber
1Department of Systems Biology, Harvard Medical School, Boston MA 02115
2Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston MA 02115
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Roderick T Bronson
3Department of Microbiology and Immunology, Harvard Medical School, Boston MA 02115
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Jonathan W Kotula
1Department of Systems Biology, Harvard Medical School, Boston MA 02115
2Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston MA 02115
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Georg K Gerber
4Massachusetts Host-Microbiome Center, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
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Jeffrey C Way
2Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston MA 02115
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Pamela A Silver
1Department of Systems Biology, Harvard Medical School, Boston MA 02115
2Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston MA 02115
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  • For correspondence: Pamela_Silver@hms.harvard.edu
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Abstract

Inflammation in the gut, caused by infection and autoimmunity, remains challenging to effectively detect, monitor, and treat. Here, we engineer a commensal mouse E. coli strain to record exposure to tetrathionate, a downstream product of reactive oxygen species generated during inflammation. Using these programmed bacteria to sense in situ levels we show that tetrathionate accompanies inflammation during Salmonella-induced colitis in mice and is elevated in an inflammatory bowel disease mouse model. We demonstrate long-term genetic stability and associated robust function of synthetic genetic circuits in bacteria colonizing the mammalian gut. These results demonstrate the potential for engineered bacteria to stably and reliably probe pathophysiological processes for which traditional diagnostics may not be feasible or cost-effective.

One sentence summary Engineered bacteria record an inflammatory response in an IBD mouse model and are genetically stable during long-term growth in the mouse gut.

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Posted September 14, 2016.
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Long-term monitoring of inflammation in the mammalian gut using programmable commensal bacteria
David T Riglar, Michael Baym, S Jordan Kerns, Matthew J Niederhuber, Roderick T Bronson, Jonathan W Kotula, Georg K Gerber, Jeffrey C Way, Pamela A Silver
bioRxiv 075051; doi: https://doi.org/10.1101/075051
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Long-term monitoring of inflammation in the mammalian gut using programmable commensal bacteria
David T Riglar, Michael Baym, S Jordan Kerns, Matthew J Niederhuber, Roderick T Bronson, Jonathan W Kotula, Georg K Gerber, Jeffrey C Way, Pamela A Silver
bioRxiv 075051; doi: https://doi.org/10.1101/075051

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