An Inflammation-Targeting Engineered Probiotic Escherichia coli Nissle 1917 with High Anti-TNF-α Nanobody Secretion Efficacy Alleviates Ulcerative Colitis.

ABSTRACT: The probiotic Escherichia coli Nissle 1917 (EcN), clinically used for ulcerative colitis (UC) due to its safety and genetic tractability, exhibits limited therapeutic efficacy owing to poor targeting and colonization at inflamed sites. Phosphatidylserine (PS) exposure increases on apoptotic colon epithelial cells during UC progression, suggesting PS-targeting could enhance EcN localization. Here, EcN is engineered to surface-display Annexin A5 (ANXA5), a PS-binding protein, to improve inflammation targeting and colonization. Since TNF-α drives UC pathogenesis and anti-TNF-α biologics face cost and safety limitations, the secretion-hindering lpp gene is concurrently knocked out in ANXA5-expressing EcN, creating the inflammation-targeted, secretion-enhanced EcNΔlpp::A5. This base strain is f

SUBMITTER: Hua S 

PROVIDER: S-EPMC12697777 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature