A Synthetic Biosensor to Find Drugs Targeting TB Persistence

Robert Abramovitch of Michigan State University in the U.S. will use their high-throughput drug discovery platform to identify new drugs for treating chronic tuberculosis and for potentially shortening the current treatment time of six to nine months. Their platform exploits a genetic region known as the DosR regulon thought to underlie the behavior of the causative bacteria in humans under low oxygen conditions, when they become dormant and thereby resistant to current drugs. In Phase I, they screened over 250,000 compounds and identified around 170 candidates that could either stop bacterial persistence under low oxygen conditions or could potently inhibit bacterial growth. In Phase II they will optimize one of the candidate DosR regulon inhibitors and test the ability of this class to block chronic infection, as well as characterizing the compounds that inhibit bacterial growth.