Grant: Project Grant

Mycobacterium tuberculosis (Mtb) causes the devastating lung disease tuberculosis (TB). Nearly two million people die from TB annually. Mtb infects and grows inside macrophages, a type of white blood cells, present in the lungs of patients. Within these human cells, the bacteria are hidden from the host immune response and are protected from drug therapy, thus, creating challenges for anti-TB drug discovery. With the increasing prevalence of multi- and extremely drug-resistant tuberculosis in several countries, there is a pressing need for new approaches to combat TB. TB is a complex disease that relies on both bacterial and host compounds to determine disease progression and infectivity. In this proposal, we offer a unique approach for drug discovery targeting both human host proteins that control Mtb infection as well as host dependent target within the bacilli. We do so by screening natural products from marine sources and known inhibitors of human proteins for their ability to restrict Mtb growth in the macrophage.