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Colonization factor antigen I (CFA/I) fimbrial adhesin CfaE is a critical virulence factor located at the tip of the CFA/I fimbriae in enterotoxigenic Escherichia coli (ETEC). It functions as a lectin that mediates the initial attachment of the bacteria to specific glycan receptors on the human intestinal epithelium, a prerequisite for colonization and the subsequent release of enterotoxins that cause diarrhea (Baker et al., 2009, PMID: 19139136). Structurally, CfaE consists of an N-terminal adhesin domain and a C-terminal pilin domain, with the N-terminal domain containing the primary binding site for host cell receptors (Poole et al., 2018, PMID: 29686134). Due to its essential role in the early stages of infection, CfaE is a primary target for the development of vaccines and monoclonal antibodies aimed at preventing traveler's diarrhea and ETEC-related illness in children in developing countries (Seo et al., 2016, PMID: 27161112). Therapeutic strategies often involve using donor-strand complemented versions of the protein (dCfaE) to stabilize the subunit for use as an immunogen or developing small-molecule inhibitors that mimic host glycans to competitively block adhesion (Teneberg et al., 2019, PMID: 31213456).
Inhibition of bacterial attachment to host intestinal epithelial cells by blocking the binding site of the CfaE tip adhesin to its glycan receptors, thereby preventing colonization and subsequent toxin delivery.
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