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Engineered E. coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut

Author

Listed:
  • Pichet Praveschotinunt

    (Harvard University
    Harvard University)

  • Anna M. Duraj-Thatte

    (Harvard University
    Harvard University)

  • Ilia Gelfat

    (Harvard University
    Harvard University)

  • Franziska Bahl

    (Harvard University
    Albert Ludwigs University of Freiburg)

  • David B. Chou

    (Harvard University
    Massachusetts General Hospital)

  • Neel S. Joshi

    (Harvard University
    Harvard University)

Abstract

Mucosal healing plays a critical role in combatting the effects of inflammatory bowel disease, fistulae and ulcers. While most treatments for such diseases focus on systemically delivered anti-inflammatory drugs, often leading to detrimental side effects, mucosal healing agents that target the gut epithelium are underexplored. We genetically engineer Escherichia coli Nissle 1917 (EcN) to create fibrous matrices that promote gut epithelial integrity in situ. These matrices consist of curli nanofibers displaying trefoil factors (TFFs), known to promote intestinal barrier function and epithelial restitution. We confirm that engineered EcN can secrete the curli-fused TFFs in vitro and in vivo, and is non-pathogenic. We observe enhanced protective effects of engineered EcN against dextran sodium sulfate-induced colitis in mice, associated with mucosal healing and immunomodulation. This work lays a foundation for the development of a platform in which the in situ production of therapeutic protein matrices from beneficial bacteria can be exploited.

Suggested Citation

  • Pichet Praveschotinunt & Anna M. Duraj-Thatte & Ilia Gelfat & Franziska Bahl & David B. Chou & Neel S. Joshi, 2019. "Engineered E. coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13336-6
    DOI: 10.1038/s41467-019-13336-6
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