Grant: Operating Grant

Incidence of tuberculosis (TB) has been increasing 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. Close to 5000 people die from TB every day. TB is the most common infection among people living with HIV/AIDS, leading to killing of one of every three of them. A disturbing fact is that TB is the only opportunistic infection of HIV (and other immunocompromised patients), which is a public health threat to people they contact as it spreads by aerosol through coughing, laughing and sneezing. Each individual with infectious TB is estimated to infect 10-14 more individuals per year. WHO has spotlighted that TB could become a major epidemic worldwide including North America and Europe if not controlled. Most alarmingly, multi-drug resistant TB (MDR-TB) with a mortality rate of ~89%, continues to rise worldwide. Further, deadly new extensively-drug-resistant TB (XDR-TB) with 100% mortality among HIV/AIDS and non-HIV people, has put this disease at a top priority. XDR-TB has been reported in 45 countries including United States, Japan, Canada and Europe. XDR-TB is virtually incurable. There is a real unmet need to discover novel anti-TB drugs. We have made innovative discovery of new classes of compounds, which exhibit potent activity against various pathogenic mycobacteria and drug-resistant strains, and would 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 cultures and in animal models. The proposed studies will contribute significantly to the knowledge and understanding of new approaches for the treatment of TB infections. Promising agents may emerge from these studies, which could then be developed as a new generation of drugs for TB and MDR/XDR-TB to improve the life expectancy and quality of life of infected people worldwide.