Search for new anti -TB molecules.

Despite the availability of antitubercular therapy for over 50 years, the incidence of TB has increased at an alarming rate since the last part of the 20th century. Currently BCG is the only approved vaccine against tuberculosis. However, it is found to be less effective in preventing the disease in adults and the efficacy is relatively low in tropical third world countries. Long duration of treatment, and emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis render the current mode of treatment of TB very difficult, prohibitively expensive and often completely ineffective. The situation is made worse by the lethal combination of drug-resistant TB and HIV infection. This scenario calls for development of novel and more effective anti-TB drugs at least until better vaccines or other forms of treatment are available.

We take a multi-pronged approach to discover new anti-TB principles: i) Taking cue from traditional systems of medicine we select plants to find out if they possess any anti-TB molecules. Using bioactivity-guided assays the plants are extracted with organic solvents and potential anti-TB molecules are purified. ii) Most of the anti-infectious agents, especially antibacterials, have their origin in soil bacteria and fungi. We are currently working on a few actinomycetes which showed promising antimycobacterial activity in vitro.

Mycobacterium-macrophage interactions

M. tuberculosis is a clever facultative intracellular pathogen, and resides within the host macrophages. In intracellular pathogenic bacteria a number of virulence genes are known to be induced at different stages following uptake by the host. Similarly gene expression in the host cell is also altered during infection. The interactions between mycobacterial and macrophage factors during infection and disease are of great interest and importance. Identification and functional characterization of proteins of the host and the pathogen involved in signaling mechanisms, transcriptional regulations, subcellular processes etc. that follow infection will greatly help understand the disease mechanism and thereby give clues as to how to device intervention strategies. Our laboratory aims to identify and study mycobacterial and host proteins involved in these processes.