Ajay K Saxena is a professor in Jawaharlal Nehru University


Tuberculosis is a chronic infectious disease caused by M. tuberculosis. M. tuberculosis contains an ESX protein secretion system for the transport of intracellular proteins across their highly impermeable cell wall. Out of five ESX pathways, ESX-1 and ESX-3 are essential for virulence and growth of M. tuberculosis. ESX-1 pathway contains at least 10 genes that encode T-cell antigens as well as AAA-ATPases. Proper functioning of the ESX-1 pathway requires the knowledge of the structure and interaction of multiple ESX-1 substrates and other component proteins prior to their secretion. We have expressed, purified and determined the X-ray structure of M. tuberculosis EspR protein. EspR is a transcriptional activator that promotes ESX-1 secretion by activating transcription of espACD operon immediately upon macrophage infection. Currently, we are involved in structural analysis of complexes of EspR with promoter DNA sequences and specifically designed molecular inhibitors. The EspC is a small protein that strongly recognized by T cells isolated from patients with M. tuberculosis. The EspC is immunodominant in active and latent tuberculosis infection. The high immunodominance characteristics of EspC, makes it an attractive vaccine candidate for M. tuberculosis. We have expressed, purified and performed the binding studies on M. tuberculosis EspC and EccA1 protein. The structure analyis of native and complexed EspC proteins are currently in progress. The structure-function analysis of EspR and EspC proteins will contribute significantly to understanding the mechanism of ESX-1 secretion pathway and drug development against M. tuberculosis. All new results will be presented in the current meeting.