Project Grant R01AI194521

The University of Washington received a $777,498 Project Grant from the National Institute of Allergy and Infectious Diseases under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded May 12, 2026, with a completion date of April 30, 2031. The project delivers structural and biochemical research characterizing a novel parasteric inhibition mechanism targeting FimH, the mannose-specific fimbrial adhesin of uropathogenic E. coli. Utilizing recently resolved cryo-electron microscopy structures, the research team will characterize monoclonal antibodies and de novo-designed miniproteins capable of both blocking and reversing bacterial adhesion and biofilm formation, optimize these inhibitors through structure-function analysis, and validate efficacy in murine models of urinary tract infection through passive intra-peritoneal immunization studies.

The research deliverables advance understanding of allosteric protein inhibition mechanisms and generate therapeutically relevant data supporting the development of conceptually novel treatments against uropathogenic E. coli and other human pathogens. By establishing the structural basis of parasteric inhibition and demonstrating protective efficacy in animal models, the project contributes to the broader objectives of the Allergy and Infectious Diseases Research program in establishing biomedical knowledge and methodological advances to improve public health outcomes related to infectious disease prevention and treatment.