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Nat Commun ; 10(1): 5580, 2019 12 06.
Article in English | MEDLINE | ID: mdl-31811125

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.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Drug Delivery Systems/methods , Escherichia coli/genetics , Escherichia coli/metabolism , Genetic Engineering/methods , Probiotics/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Bacterial Proteins/genetics , Caco-2 Cells , Colitis/chemically induced , Colitis/drug therapy , Colitis/immunology , Colitis/pathology , Dextran Sulfate/adverse effects , Disease Models, Animal , Epithelium , Female , Humans , Immunomodulation , Inflammatory Bowel Diseases/drug therapy , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Mice , Mice, Inbred C57BL , Probiotics/pharmacology , Trefoil Factors/genetics
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