Federal Grant Award Summary

The University of Wisconsin-Madison received a $414,305 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded February 9, 2026, with completion targeted for January 31, 2028. The grant funds research to characterize the substrate promiscuity and transport mechanism of PACE (Proteobacterial Antiseptic Efflux) family transporters, a class of bacterial transporters discovered approximately a decade ago. The research encompasses biochemical and biophysical analyses to determine the full substrate profile of PACE transporters, identify substrate binding sites, elucidate proton coupling mechanisms, determine H+/substrate stoichiometry, and establish the three-dimensional structure of these transporters through complementary experimental approaches including mutagenesis, in vitro transport assays, and native mass spectrometry.

This investigation addresses significant gaps in understanding PACE transporter function and substrate specificity, with implications for bacterial resistance mechanisms and antimicrobial development. The project builds upon preliminary findings indicating that PACE transporters exhibit variable substrate recognition patterns, including both conferral of and enhanced susceptibility to certain antimicrobial compounds. By systematically characterizing these transporters through structural, biochemical, and functional studies, the research is expected to advance fundamental knowledge of bacterial efflux transporter biology and inform strategies to counter antibiotic resistance in clinically significant pathogens such as Acinetobacter baumannii and Pseudomonas aeruginosa.