Production and secretion of heterologous immunomodulators in bacteroides thetaiotaomicron

Abstract

Chronic and acute inflammation in the colon significantly impact human and animal health, and productivity in agriculture. Unfortunately, current treatments are not very effective for long-term management and treatment is costly. This research project has helped address these limitations by engineering a colonic bacterium, Bacteroides thetaiotaomicron, to produce tumor necrosis factor receptor 2 (TNFR2), α-1-antitrypsin (A1AT) and elafin. These anti-inflammatory proteins were stitched to BtAnchor and BvSecrete signal peptides that facilitate their trafficking to the outer surface and external environment of the cell, respectively. Protein targets were initially produced and localized within the Gram-negative, model organism, Escherichia coli, and elafin demonstrated statistically significant inhibition of elastase. Protein targets: A1AT, TNFR2, and elafin were successfully produced in a dual-glycan responsive B. theta strain previously developed in the Abbott lab. The strains developed as part of this project represent novel tools for reducing of inflammation in agricultural livestock and human medicine.