Grant: Project Grant

The incidence and severity of tuberculosis (TB) have increased dramatically in recent years posing a major global health challenge. According to the World Health Organization (WHO), TB kills more adults per year than any other single pathogen worldwide and could become a major global epidemic including North America and Europe if is not controlled. There were more cases of TB in 2008 than at any point in history. Close to 5000 people die globally from TB every day. TB is the most common infection among people living with HIV/AIDS and kills one of every three of them. A disturbing fact is that TB is the only opportunistic infection of HIV (and other immune compromised patients), which is a public health threat because it spreads through coughing, laughing and sneezing. Each person with TB infects ~10-14 more individuals/year. Most alarmingly, multi-drug resistant TB (MDR-TB) with a mortality rate of ~89%, and deadly extensively-drug-resistant TB (XDR-TB) and totally-drug-resistant TB (TDR-TB) with 100% mortality, have put this disease on high alert. XDR-TB has been reported in >50 countries including USA, Japan, Canada and Europe. The growing number of cases of MDR, XDR and TDR-TB worldwide and treatment failure, is of utmost concern. Consequently, there is a real unmet need to discover novel anti-TB drugs. We have made an innovative discovery of new classes of agents that exhibit potent activity against various pathogenic mycobacteria, including drug-resistant strains, and work by a novel mechanism distinct from the current drugs. In the proposed work, we will investigate anti-mycobacterial properties of these promising molecules in cell cultures and in animal models. The proposed studies will contribute significantly to the knowledge and understanding of new treatments for TB infections. Promising agents will emerge from these studies as a new generation of drugs for TB and MDR/XDR/TDR-TB that improve the life expectancy and quality of life of people worldwide