Federal Grant Award Summary

The University of Pittsburgh received a $799,572 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), effective April 1, 2026 through March 31, 2031. The project, titled "Time Resolved Structural Analyses of β-Lactam/β-Lactam Inhibitor Binding to AmpC," focuses on generating critical structural and mechanistic insights into how AmpC β-lactamases confer antibiotic resistance in gram-negative bacteria including Pseudomonas aeruginosa and Acinetobacter baumannii.

The research deliverables address significant knowledge gaps in understanding β-lactamase function by characterizing the kinetic mechanisms and intermediate states involved in β-lactam hydrolysis and inhibition, moving beyond existing structural data limited to acyl-enzyme complexes. This work is intended to elucidate how mutations in extended-spectrum AmpCs increase catalytic efficiency and reduce susceptibility to β-lactamase inhibitors, with the ultimate objective of informing the development of more effective therapeutic strategies to combat antibiotic resistance—a critical public health threat contributing to nearly five million deaths annually worldwide. The five-year project will be conducted at the University of Pittsburgh's Pittsburgh, Pennsylvania location.