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Antibiotics Targeted to Bacterial Stress Pathways

ID# 2010-3727
Overview of Invention

Technology Summary

An assay to identify inhibitors of a conserved bacterial stress response pathway, sigma factor sE, has been developed. The anti-bacterial agents identified will be able to combat highly resistant bacteria. In Escherichia coli, sE is essential to maintain the homeostasis of the cell envelope during stress and growth. This novel system finds inhibitors of the sigma factor sE pathway in order to render these pathogens harmless. In this reporter system when sE activity is high, RybB will be produced, and there will be low fluorescence. The opposite is also true; if sE activity is low, ompC-yfp transcription will be undisturbed and high fluorescence will be observed. The purpose is to identify inhibitors that block the sE pathway and study the mechanism by which these inhibitors act.

Application & Market Utility

No inhibitors are currently avaibale for this sE pathway and as assays can currently identify such inhibitors. The assay described here provides a positive read-out of inhibition of the sE system and can be adapted for high-throughput screening (HTS). Experimental results from a leading pharmaceutical company have demonstrated the feasibility of this assay. The innovative primary screen and secondary assays can be readily adapted to identify inhibitors of other sRNA regulators and sigma factors or other transcriptional regulators.

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