Bacterial adhesion to urothelial cell surface glycoconjugates

Bacterial adhesion to urothelial cell surface glycoconjugates is a critical initial step in the pathogenesis of urinary tract infections (UTIs), primarily mediated by uropathogenic Escherichia coli (UPEC) (Wu et al., 1996, PNAS). This interaction involves bacterial surface adhesins, such as FimH at the tip of Type 1 pili, which recognize and bind to mannosylated glycoproteins on the host urothelium, most notably Uroplakin Ia (Hung et al., 2002, Molecular Microbiology; Zhou et al., 2001, Journal of Cell Science). This attachment allows bacteria to resist being flushed out by urine flow and facilitates their invasion into the bladder wall, where they can form protective intracellular bacterial communities (IBCs) (Martinez et al., 2000, EMBO Journal; Anderson et al., 2003, Science). Targeting this adhesion process represents a promising non-antibiotic therapeutic strategy, often referred to as anti-adhesion therapy (Ofek et al., 2003, FEMS Immunology & Medical Microbiology). Drugs such as D-mannose and small-molecule FimH antagonists (e.g., Sibofimloc) act as competitive inhibitors, binding to the bacterial adhesin and preventing its attachment to the host cell surface (Klein et al., 2010, Journal of Medicinal Chemistry; Kranjčec et al., 2014, World Journal of Urology). By blocking colonization and invasion, these agents help the body naturally clear the infection and may reduce the recurrence of UTIs without the selective pressure for antibiotic resistance associated with traditional bactericidal drugs (Spaulding et al., 2017, Nature; Hickling & Nitti, 2013, Reviews in Urology).

Other names

Uropathogenic bacterial adhesionFimH-uroplakin interactionBacterial attachment to bladder epitheliumUPEC adhesion to urothelium

Competitive inhibition of bacterial adhesins (e.g., FimH) binding to host cell surface glycoconjugates (e.g., Uroplakin Ia)