anti-B. fragilis toxin peptide

Anti-B. fragilis toxin peptides (also known as prodomain interface binders or PIBs) are de novo designed miniproteins developed to inhibit the metzincin family protease Bacteroides fragilis toxin (BFT), the primary virulence factor of enterotoxigenic Bacteroides fragilis (ETBF). These peptides bind to a distal allosteric site at the prodomain interface of BFT rather than the active site. This binding blocks BFT from interacting with its host cell receptor, claudin-4 (CLDN4), thereby preventing toxin-mediated E-cadherin cleavage, epithelial barrier disruption, and downstream proinflammatory signaling. These peptides have been engineered as disulfide-stabilized variants (e.g., MB03-ds, MB15-ds) for oral administration or for in situ secretion by engineered live biotherapeutic products (such as an engineered Bacteroides ovatus strain) to prevent ETBF-associated gut pathology, including acute diarrhea, inflammatory bowel disease, and colorectal tumor formation.

Other names

anti-B. fragilis toxin miniproteinsprodomain interface bindersprodomain interface binding inhibitors