Recently, our identification of small-molecule inhibitors of trans-translation has opened new opportunities for translational research and basic science. We identified and characterized inhibitors of trans-translation, and showed they have broad-spectrum antibiotic activity. We have several projects to advance drug development with these compounds.
The inhibitors we identified also provide new tools to understand the role of trans-translation in bacterial physiology and genetics. We are using these inhibitors to examine the physiological response of bacteria to losing trans-translation activity, and for chemical genetic experiments to understand why trans-translation is universally conserved in bacteria.
Our experience with inhibitors of trans-translation led us to explore other pathways that are candidate targets for antibiotic development and chemical biology studies. In collaboration with Sarah Ades (Penn State), we engineered and validated assays for inhibition of two mechanisms that are important for maintenance of the cell envelope in Gram-negative bacteria: αE-directed transcription, and Hfq-sRNA repression of gene expression.