Adherent-invasive Escherichia coli surface structures

Adherent-invasive Escherichia coli (AIEC) surface structures, most notably Type 1 pili and flagella, are essential for the pathogenesis of Crohn's disease by enabling bacterial attachment to and invasion of the intestinal epithelium [PMID: 24859503]. The FimH adhesin, located at the tip of Type 1 pili, specifically recognizes and binds to mannosylated residues on the host receptor Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which is overexpressed in the ileal mucosa of affected individuals [PMID: 15542707]. This interaction facilitates the formation of biofilms and the subsequent translocation of bacteria into the lamina propria, where they survive within macrophages and drive chronic inflammation [PMID: 21903790]. Therapeutic targeting of these surface structures, particularly through small-molecule FimH antagonists like Sibofimloc (EB8018/TAK-018), represents a novel anti-adhesive approach designed to clear pathogenic AIEC while sparing the commensal microbiota [PMID: 31513025]. By blocking the initial step of infection, these agents aim to prevent the inflammatory cascade and mucosal damage associated with Crohn's disease [PMID: 28607163].

Other names

AIEC adhesinsAIEC surface proteinsType 1 piliFimH adhesinFlagellar proteinsAIEC invasins

Anti-adhesive mechanism involving the competitive inhibition of the bacterial FimH adhesin, preventing its interaction with host CEACAM6 receptors and subsequent mucosal colonization [PMID: 31513025].