Journal of Analytical & Bioanalytical Techniques
Open Access

Abstract

Tuberculosis is a chronic infectious disease caused by M. tuberculosis. M. tuberculosis contains 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 structure and interaction of multiple ESX-1 substrates and other component proteins prior to their secretion. We are involved in purification and X-ray crystallographic studies on key proteins involved M. tuberculosis ESX-1 secretion pathway. We have purified, crystallized and working for X-ray structures of two key proteins, EspR and EspC. EspR is a transcriptional activator that promotes ESX-1 secretion by activating transcription of the espACD operon immediately upon macrophage infection. When the ESX-1 is active, EspR is secreted and result in reduced expression of espACD. Conversely when the ESX-1 pathway is inactive, the cytosolic level of EspR increases, that results in increased expression of espACD. EspC is small protein that strongly recognized by T cells isolated from patients with M. tuberculosis. EspC is immunodominant in active and latent tuberculosis infection. The protein contains broadly recognized CD4+ and CD8+ epitopes and induces a predominantly CD4+ T-cell response. The high immunodominance characteristics of EspC, makes it an attractive vaccine candidate for M. tuberculosis . The EspC has the high specificity and confers strong potential for T-cell?based immunodiagnosis. The structure-function analysis of EspR and EspC proteins will contribute significantly in understanding the ESX-1 pathway mechanism and drug development against tuberculosis disease.

Biography

Ajay K. Saxena has completed his Ph.D. degree from AIIMS, Delhi in 1995. He completed his Postdoctoral studies from Austrian Academy of Sciences, Europe in 1996-98 and NIAID, National Institutes of Health, USA in 1998-2005. Since 2005, he has been working as Associate Professor at Structural Biology Section of School of Life Sciences, Jawaharlal Nehru University at Delhi, a premier university of India. He has published several papers in reputed national and international journals and reviewer of several national and international journals. He has obtained several national and international funding and awards for his excellent research performance.