Screen for Inhibitors of Mycobacterial RNA Polymerase

Tuberculosis (TB) is the leading cause of death from any single infectious agent for much of the wois estimated that one third of the world's population carries a latent TB infection. Most alarming adrug-resistant TB. Rifampicin is currently a treatment of choice, but there is a growing resistancerifampicin and its analogs and therefore an important need for new therapies. The goal of this reseadiscover novel classes of antibiotics for the treatment of drug-resistant mycobacteria. A high throuestablished for the discovery of new inhibitors of rifampicin-resistant RNA polymerase of M. tubercuUsing purified M. smegmatis as a model system, RNA polymerase resistant to rifampicin and rifabutinpurified and used to develop a robust, reliable assay for screening a library of synthetic organic cproducts for compounds which inhibit RNA polymerase. Once active compounds have been identified, thefor potency, specificity and toxicity, and promising compounds will ultimately be developed into antthrough medicinal chemistry.