Intracellular bacterial pathogens express unique genes following uptake by the host macrophages that facilitate their survival and multiplication. Expression of bacterial factors associated with virulence and pathogenesis can coordinately influence and regulate expression of infection-associated genes in the host cell.
Macrophages are the primary line of defense against invading pathogens, however, in successful infections M. tuberculosis resides in the macrophages and multiplies. Using THP1 macrophage cells as a model system, and proteomic tools such as 2D electrophoresis and MALDI-TOF mass spectrometry, we have identified a hypothetical protein of M. tuberculosis from the macrophage after infection. When expressed in M. smegmatis it enhanced the survival of the bacterium in the macrophages. Employing bioinformatic, genetic and biochemical tools we are analyzing this protein further to gain insights into its function during infection.

Ethyl p-methoxycinnamate (EPMC), isolated from K. galanga, possesses anti-TB activity in vitro. It exhibits a minimum inhibitory concentration (MIC) of 50-100 microgram/mL against susceptible and drug resistant clinical isolates of M. tuberculosis. In this project we aim at improving the antimycobacterial potential of EPMC and cinnamic acid (in collaboration with Dr KN Rajasekharan, Department of Chemistry, University of Kerala). After synthesizing about 27 derivatives of we obtained a molecule with 8-fold better activity on M. tuberculosis H37Rv.