INHIBITORS OF FIMH AGAINST UROPATHOGENIC ESCHERICHIA COLI: COMBINATION THERAPY, ANTI-VIRULENCE MECHANISMS, AND RESISTANCE BIOLOGY

The majority of urinary tract infections (UTIs) are caused by Uropathogenic Escherichia coli (UPEC), which are difficult to treat due to recurrence and growing antibiotic resistance. FimH, the mannose-binding adhesin at the tip of type 1 pili, is an appealing target for anti-virulence because it promotes bladder colonization, invasion, and the creation of intracellular biofilm-like communities. The structural biology of FimH, the ways in which competitive antagonists block it, and the medicinal chemistry that advanced the field from simple alkyl mannosides to ortho-substituted biphenyl, C-linked, and heterocyclic molecules with nanomolar potency are all included in this study. After that, check how resistance and adaptation could develop in response to an anti-adhesion medication, which in vitro and animal evidence support the anti-virulence effects, and how FimH antagonists could be used with antibiotics or inhibitors of other adhesins like FmlH. Pharmacokinetic and safety factors are explored, with special focus to the trade-off between potency and permeability, and computational and experimental evaluation techniques are described. Lastly, highlight the primary gaps direct resistance data, thorough combination studies, and human efficacy trials and offer recommendations for next-generation design.