Using knowledge of the cholesterol metabolism pathway and a drug scaffold which has high host in vivo stability, low host toxicity, and excellent host bioavailability, our group has identified lead compounds that have high bactericidal activity in combination with approved TB drugs (e.g., isoniazid and bedaquiline) under both aerobic and anaerobic conditions. The lead compounds target a cholesterol-dependent persistence pathway, and their mechansim is distinct from current TB drugs on the market or in development. Current work is focused on translating the compounds into development and further elucidating the mechanism of action.
The insights gained from fundamental studies are being translated into practical improvements in the TB clinic. Most recently, we have developed an antibody-based assay to detect infection by Mtb in human serum.