Engineering a Functionalized Biofilm-Based Material for Modulating Escherichia Coli’s Effects in the Mammalian Gastrointestinal Tract

Abstract

This study investigates the potential use of engineered bacterial biofilms as programmable platforms to control bacterial-epithelial interactions in the mammalian gut. It is clear that commensal microflora play a critical role in the healthy functioning of the gastrointestinal tract, so this work seeks to use engineered biofilms to enhance and direct the therapeutic effects of such microbes. It is hypothesized that E. coli strains can be engineered to produce biofilm-based materials functionalized with peptides that will enhance colonization and modulate localized adhesion in the gut, while providing direct thera- peutic effects themselves. A library of peptides has been identified, including the trefoil factor family peptides, as strong candidates for biofilm functionalization and E. coli have been successfully engineered to display these peptides on curli fibers that compose the extracellular biofilm. In vitro studies with epithelial cell cultures have demonstrated that E. coli secreting these modified curli fibers have enhanced epithelial adhesion, representing a strong starting point for the development of the desired programmable platform. Such a programmable platform has numerous potential downstream applications, such as producing and immobilizing therapeutic peptides and targeting specific inflammation sites, which could positively affect the treatment of inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, which affect more than 1.4 million Americans.