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

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…

• NI
  National Institutes of Health

  Awards: 1R01DK110770-01A1, 1R01DK110770
• HW
  Hansjörg Wyss Institute for Biologically Inspired Engineering, Harvard University
• HD
  Harvard Digestive Diseases Center, Harvard University