Research Projects

M. tuberculosis has developed a specialized system called the type VII secretion system (T7SS) to transport virulence factors across their complex cell envelopes. T7SS is classified into ESX-1 to ESX-5, which adopts a hexameric assembly of ~1.5-MDa complex. The ESX SS comprises four membrane-associated core components, EccA and EccC, which hydrolyze ATP to transport virulence factors EspC, EspB, ESAT6, and CFP10 across the channel. The study aims to visualize the cross-talks between EccA1 and EccCb1 with virulence factors to decipher the substrate translocation mechanism through SS. The structure and function of virulence factors in the presence of liposomes will be studied to elucidate bacterial pathogenesis. The hypothesis is that T7SS is the essential bacterial machinery directly associated with bacterial pathogenesis, responsible for the translocation of virulence factors from bacteria. The study proposes to characterize the detailed interactions of virulence factors with SS and liposomes at high resolution in a near-native environment. This knowledge will help develop an alternative therapeutic strategy to develop novel inhibitors to prevent bacterial pathogenicity and help overcome multidrug resistance (MDR) Mtb. The study will involve cloning and overexpression of EccA1, EccCb1, and virulence factors, purification using Ni-NTA followed by SEC, and various biochemical and biophysical studies. The structural and functional knowledge will also help in gene editing of Mtb using its CRISPR System and knock out/down mutant strategy to develop null mutants to understand bacterial pathogenesis.