Inhibitors of Bacterial Efflux Pumps
We used SAFIRE to screen a drug-diversity library and identified three small molecules that are efflux pump modulators (EPMs). These EPMs kill bacteria in macrophages and in epithelial cells. In broth culture, the EPMs prevent export of efflux pump substrates by Salmonella, Klebsiella and Enterobacter clinical isolates that are antimicrobial resistant. In collaboration with Dr. Ed Yu’s laboratory, we found that the compounds bind a subunit of a clinically relevant efflux pump. We are currently optimizing analogs of these small molecules.