Targeting Force-Regulated FimH Adhesin: Assays, Mannosides, and Biologics for Anti-Virulence Therapy of UPEC Infection
Year: 2026
Type: article
Abstract: Urinary tract infections (UTIs) are among the most common bacterial infections, and recurrent UTIs caused by uropathogenic Escherichia coli (UPEC) drive antibiotic use and antimicrobial resistance. FimH, the mannose-binding adhesin at the tip of type 1 pili, is a central UPEC virulence factor. Under shear force, FimH switches from a low-affinity, tense state to a high-affinity, relaxed state, strengthening adhesion during urine flow. This catch-bond behavior makes FimH a promising anti-virulence target, though a difficult one to drug. Here, we review strategies to target FimH, including monovalent and multivalent mannosides, vaccines, conformation-selective monoclonal antibodies, and de novo engineered miniproteins, together with the assays used to quantify FimH-ligand binding and UPEC adhesion. Clinical translation has been limited by assay-dependent potency, urinary pharmacokinetics, and intracellular reservoirs. We posit that effective FimH-targeted therapy requires alignment among inhibitor mechanism, FimH conformational state, bladder lumen exposure, and infection stage, which in turn defines realistic roles in prevention, early intervention, and combination therapy.
Source: ACS Infectious Diseases
Authors: Mohor Mitra, Zhilei Chen
Institution: Texas A&M University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W7222802201