Identification of Novel Synthetic and Natural Product Semi-Synthetic Derivatives Targeting Mycobacterium smegmatis and M. tuberculosis Spectinomycin and Rifampicin Efflux Pumps
Elizabeth Kigondu of the Kenya Medical Research Institute will identify natural products that block the resistance mechanism developed by tuberculosis-causing bacteria against existing anti-mycobacterial drugs to help more effectively treat tuberculosis. Tuberculosis (TB) is a highly prevalent and severe disease that has been exacerbated by the emergence of multi-drug resistant TB for which only limited treatments are available. Efflux pumps play a critical role in mycobacterial resistance to two drugs, spectinomycin and rifampicin. They will identify natural products and their derivatives that block these efflux pumps by first searching databases for analogs to published efflux pump inhibitors, and then performing virtual docking experiments to identify those that bind. These will then be tested in drug combinations with spectinomycin and rifampicin for synergistic cytotoxicity and anti-mycobacterial activity.