Genetically engineered probiotics as<unk> s to treat intestinal inflammation. a Genetically engineered E. coli Nissle 1917 (EcN) with csg (curli) operon deletion (PBP8 strain) containing plasmids encoding a synthetic curli operon capable of producing chimeric CsgA proteins (yellow chevrons with appended bright green domains), which are secreted and self-assembled extracellularly into therapeutic curli hybrid fibers. b CsgA (yellow), the main proteinaceous component of the E. coli biofilm matrix, was genetically fused to a therapeutic domain—in this case, TFF3 (PDB ID: 19ET, bright green), which is a cytokine secreted by mucus-producing cells. The flexible linker (black) includes a 6xHis tag for detection purposes. c Engineered bacteria are produced in bulk before delivery to the GI tract. A site of colonic inflammation is highlighted in red. d Interaction of E. coli and the colonic mucosa. Inflammatory lesions in IBD result in loss of colonic crypt structure, damage to epithelial tissue, and compromised barrier integrity (left panel, (−) E. coli). The resulting invasion of luminal contents and recruitment of immune cells to the site exacerbates the local inflammation. The application of E. coli (right panel, (+) E. coli) reinforces barrier function, promotes epithelial restitution, and dampens inflammatory signaling to ameliorate IBD activity. A<unk>  is a type of biologic that consists of a<unk>  organism that is used to treat a disease. This usually takes the form of a cell (animal, bacterial, or fungal) or a virus that has been genetically engineered to possess therapeutic properties that is injected into a patient. Perhaps the oldest use of a<unk>  is the use of leeches for bloodletting, though<unk> s have advanced tremendously since this time. Examples of<unk> s include cellular therapeutics (including immunotherapeutics), phage therapeutics, and bacterial therapeutics, a subset of the latter being probiotics.
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