Uropathogenic Escherichia coli FimH adhesin (FimH)

The Uropathogenic Escherichia coli FimH adhesin is the primary molecular target involved in the colonization of the bladder mucosal niche. This protein, located at the tip of type 1 fimbriae, mediates the attachment of UPEC to mannosylated uroplakins on the bladder epithelium, a process essential for the initiation of urinary tract infections [1][2]. Once attached, the bacteria can invade the host cells to form intracellular bacterial communities (IBCs), which serve as a protected environment for rapid replication [3]. This niche also allows for the formation of quiescent intracellular reservoirs (QIRs) that can persist despite antibiotic treatment, leading to recurrent infections [4]. Drugs targeting this interaction, such as the FimH inhibitor sibofimloc or D-mannose, work by competitively inhibiting the adhesin, thereby preventing the bacteria from establishing themselves within the bladder mucosa [5]. These anti-adhesive therapies represent a promising non-antibiotic approach to managing chronic and recurrent UTIs by targeting the specific molecular mechanism of niche entry. Sources: [1] Spaulding, C. N., et al. (2017). Nature, 545(7653), 243-247. [2] Sauer, M. M., et al. (2019). Nature Communications, 10(1), 1-15. [3] Anderson, G. G., et al. (2003). Science, 301(5629), 105-107. [4] Justice, S. S., et al. (2004). PNAS, 101(5), 1333-1338. [5] Mydock-McGrane, L. D., et al. (2016). Expert Opinion on Therapeutic Patents, 26(2), 175-197.

Other names

Type 1 fimbrial adhesinMannose-binding adhesinUPEC FimHuropathogenic Escherichia coli and bladder mucosal niche

Competitive inhibition of the FimH adhesin to prevent bacterial attachment to mannosylated uroplakins on the bladder epithelium.