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. Author manuscript; available in PMC: 2023 Sep 1.
Published in final edited form as: Trends Pharmacol Sci. 2022 Feb 26;43(9):772–786. doi: 10.1016/j.tips.2022.02.002

Figure 2. Engineered EcN variants for the treatment of inflammatory bowel disease.

Figure 2.

(a) PBP8 CsgA-TFF3 is engineered to display TFF3 on its surface. TFF3 is fused to CsgA such that it is assembled and exposed on curli fibers attached to EcN. The expression of the plasmid-encoded CsgA-TFF3, and other components of the curli operon, including the assembly/transport component CsgG, is expressed in an arabinose-dependent manner from a plasmid. (b) EGF-EcN is engineered to constitutively express a lipase ABC transporter. EGF is fused to a C-terminal LARD (Lipase ABC transporter Recognition Domain). The genes encoding the transporter and EGF are integrated into the EcN chromosome. (c) Lresb pDGAT is engineered with a blue-light responsive circuit that controls expression of Ag43, an adhesin (‘bio-glue’) that promotes EcN biofilm formation. Since blue-light does not penetrate the intestines, upconversion molecules (UCMs) that convert the NIR light to blue light are co-administered with the bacteria. Lresb pDGAT secrete TGF-ß1 fused to an OmpA secretion signal peptide. The genes encoding this system are encoded on a plasmid maintained via antibiotic selection.