Uropathogenic Escherichia coli fimbrial adhesin (FimH)

Uropathogenic Escherichia coli (UPEC) fimbrial adhesins are critical virulence factors located at the tips of hair-like appendages called fimbriae or pili. These proteins, most notably the FimH adhesin of Type 1 fimbriae and the PapG adhesin of P fimbriae, mediate the specific attachment of bacteria to host receptors on the uroepithelium (UniProt P08191, P07110). FimH specifically recognizes terminal D-mannose residues on glycoproteins like Uroplakin Ia, which is essential for the colonization of the bladder and the development of cystitis (PubMed: 29158460). PapG binds to Gal(alpha1-4)Gal-containing glycolipids, a process primarily associated with the infection of the upper urinary tract and pyelonephritis (PubMed: 11544341). By facilitating stable adhesion, these proteins allow UPEC to resist the mechanical flushing of urine and initiate invasion into host cells. Consequently, fimbrial adhesins are major therapeutic targets for anti-adhesive drugs, such as mannosides and small-molecule inhibitors like GSK3882347 and Siboflanstat, which aim to prevent or treat infections without inducing the selective pressure associated with traditional antibiotics (PubMed: 32814554).

Other names

Type 1 fimbrial adhesinP fimbrial adhesinPapGS fimbrial adhesinFimH adhesinUropathogenic Escherichia coli fimbrial adhesins at the bacteria-host uroepithelial adhesion interface

Competitive inhibition of bacterial adhesion to host urothelial receptors by mimicking natural carbohydrate ligands, thereby preventing colonization and facilitating bacterial clearance.