Induction of necrotic death in macrophages is a primary virulence determinant of Mycobacterium tuberculosis. The ESX-1 secretion system and its substrate ESAT-6 are required for M. tuberculosis to induce necrosis, but host factors that mediate the ESAT-6-promoted necrosis remain unknown. Here we report that ESAT-6-promoted necrotic death in THP-1 human macrophages is dependent on the NLRP3 infl...

The early secreted antigenic target 6 kDa protein (ESAT-6) is a potent T-cell protein antigen synthesized by Mycobacterium tuberculosis. Its corresponding gene (esat-6) is located in RD1, a 10 kb DNA region deleted in the attenuated tuberculosis vaccine strain Mycobacterium bovis BCG. The promoter region of M. tuberculosis esat-6 was cloned and characterized. A new gene, designated lhp and cotr...

Can IGRA assays, used in the highly specific and sensitive quantiFERON and T-spot tests, predict the development of disease in individuals who are infected but currently display no symptoms? High ESAT-6 reactivity may predict disease because ESAT-6 is a marker for bacterial burden. We found that vaccinated cattle for which the vaccine did not offer protection displayed high reactivity to ESAT-6...

The early secretory antigenic target (ESAT)-6 purified protein and peptides from Mycobacterium tuberculosis were evaluated as antigens for the immunodiagnosis of tuberculosis (TB). Because the control of TB requires improved diagnostic procedures, efforts have increased to identify Mycobacterium tuberculosis-specific epitopes for the immunodiagnosis of active TB and to discriminate between acti...

We have examined the intranasal administration of a vaccine against Mycobacterium tuberculosis (M.tb) consisting of the mucosal adjuvant LTK63 and the Ag Ag85B-ESAT-6. Vaccination with LTK63/Ag85B-ESAT-6 gave a strong and sustained Th1 response mediated by IFN-gamma-secreting CD4 cells, which led to long-lasting protection against tuberculosis, equivalent to that observed with bacillus Calmette...

The tuberculin skin test (TST) using purified protein derivative (PPD) of Mycobacterium tuberculosis is traditionally used to diagnose latent tuberculosis (TB) infection (LTBI). However, LTBI diagnosis by peripheral blood mononuclear cell (PBMC) interferon (IFN)-gamma responses to M. tuberculosis-specific antigens, early secreted antigenic target 6 kDa (ESAT-6) and culture filtrate protein (CFP...

Objective(s): Tuberculosis (TB) is still one of the problematic infectious diseases in developing countries, especially in Iran. In the present study, we applied ribosome display technique to select single chain variable fragments (scFvs) specific for the 6-kDa early secretory antigenic target (ESAT-6) antigen of Mycobacterium tuberculosis from a mouse scFv library. Materials and Methods: The g...

Culture filtrate from Mycobacterium tuberculosis contains protective antigens of relevance for the generation of a new antituberculosis vaccine. We have identified two previously uncharacterized M. tuberculosis proteins (TB7.3 and TB10.4) from the highly active low-mass fraction of culture filtrate. The molecules were characterized, mapped in a two-dimensional electrophoresis reference map of s...

Previous work in our laboratory showed that the ESAT-6 protein of Mycobacterium tuberculosis and Mycobacterium bovis induces strong antibody responses in a large proportion ( approximately 90%) of experimentally or naturally infected nonhuman primates. Here, the antibody response to ESAT-6 in tuberculous monkeys was characterized at the epitope level by measuring antibodies to overlapping, synt...