Escherichia coli type 1 fimbriae adhesin FimH (FimH)

Escherichia coli type 1 fimbriae are hair-like surface organelles that mediate the attachment of bacteria to host tissues, a crucial first step in infection. The functional unit responsible for this adhesion is the FimH protein, a mannose-specific lectin located at the distal tip of the fimbrial shaft (UniProt: P08191). In the urinary tract, FimH binds to mannosylated uroplakins on the surface of bladder epithelial cells, allowing uropathogenic E. coli (UPEC) to resist being washed away by urine flow and to invade host cells (PubMed: 28841135). Beyond UTIs, type 1 fimbriae are implicated in Crohn's disease, where adherent-invasive E. coli (AIEC) utilize FimH to colonize the intestinal mucosa by binding to CEACAM6 (PubMed: 21115623). Because of its pivotal role in colonization, FimH is a major target for "anti-adhesive" therapies, including small-molecule mannosides like GSK3882347 and sibofimloc (EB8018) (ClinicalTrials.gov: NCT03943446). These inhibitors competitively occupy the mannose-binding pocket of FimH, effectively "disarming" the bacteria and preventing the establishment of infection without killing the bacteria directly, which may reduce the risk of antibiotic resistance.

Other names

Type 1 piliMannose-binding adhesinFimH proteinMannose-sensitive fimbriae

Competitive inhibition of the FimH lectin domain to prevent bacterial adhesion to host mannosylated glycoproteins