Federal Grant Award Summary

The University of Illinois received a $440,908 Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), effective February 3, 2026, through January 31, 2028. The research aims to identify and develop inhibitors of bacterial peptidyl-transfer RNA (tRNA) hydrolase (PTH), an essential bacterial enzyme critical for protein synthesis. The project delivers a novel high-throughput screening (HTS) assay based on Forster Resonance Energy Transfer (FRET) using an oligonucleotide-based PTH substrate, with preliminary screening having identified compounds with inhibitory activity against PTH from Escherichia coli and Klebsiella pneumoniae.

The award supports synthesis and optimization of lead compound derivatives with sub-micromolar IC50 values to enhance activity against K. pneumoniae PTH and improve cellular uptake, while expanding screening campaigns to identify novel inhibitor scaffolds. Research services include characterization of compound interactions with PTH through Surface Plasmon Resonance (SPR) and X-ray crystallography, mechanisms of action analysis, cellular target identification, protein synthesis effects assessment, and resistance mechanism evaluation. The anticipated deliverable is identification of a lead inhibitor scaffold suitable for preclinical development as a foundation for a novel antibiotic platform, representing advancement toward a new therapeutic approach to combat bacterial infections resistant to existing antibiotics.