Escherichia coli P-fimbriae (Pap)

Escherichia coli P-fimbriae, also known as pyelonephritis-associated pili (Pap), are complex proteinaceous surface appendages primarily expressed by uropathogenic Escherichia coli (UPEC) (Hultgren et al., 1993). These structures are essential virulence factors that facilitate the colonization of the upper urinary tract by mediating specific adherence to the alpha-D-galactopyranosyl-(1-4)-beta-D-galactopyranoside (Gal-Gal) moiety of the P-blood group antigen on host renal epithelial cells (Wullt et al., 2000). The adhesion is specifically executed by the PapG protein, located at the distal tip of the fimbrial structure (UniProt P04127). Because this attachment is a prerequisite for infection, P-fimbriae are significant targets for anti-adhesive therapies designed to prevent pyelonephritis and urosepsis (Roberts et al., 1994). Current pharmacological research focuses on "pilicides," which are small molecules that inhibit the chaperone-usher pathway required for fimbrial assembly (Pinkner et al., 2006). Additionally, glycomimetic compounds are being developed to competitively block the PapG binding site, preventing bacterial docking (Svensson et al., 2001). These interventions aim to provide an alternative to traditional antibiotics, potentially reducing the selection pressure for antibiotic resistance.

Other names

Pyelonephritis-associated piliPap piliP-piliGal-Gal piliP-fimbrial adhesin

Inhibition of the chaperone-usher assembly pathway and competitive antagonism of the PapG adhesin binding to host Gal-Gal receptors.