Bringing mycobacterial secretion inhibitors to maturation

Tuberculosis caused by Mycobacterium tuberculosis is one of the deadliest infectious diseases worldwide. With the increasing rate of drug-resistant Mycobacterium tuberculosis isolates, there is an urgent need for development of novel effective drugs to combat against this disease. In this thesis, we initially introduced about the type VII ESX-5 system of Mycobacterium tuberculosis and explained why this system is a good candidate for development of new anti-tubercular drugs. We established an assay to screen for potential compounds targeting this ESX-5 system. In the end, two hits were selected and further characterized. Moreover, special properties of anti-tubercular drugs including whether these drugs are prodrugs or their in vivo activities were further investigated and emphasized. In the end, we identified potential anti-tubercular compounds with promising activities that can progress into further pre-clinical studies, clinical phases and possible treatment of human tuberculosis in the future.