Roles and underlying mechanisms of ESAT-6 in the context of Mycobacterium tuberculosis-host interaction from a systems biology perspective.

The 6kDa early secreted antigenic target (ESAT-6), an important and intensively studied virulence factor of Mycobacterium tuberculosis, acts alone or in combination with CFP-10 to influence the outcome of the host-pathogen interaction. Secreted ESAT-6 can disturb the activation of macrophages, induce apoptosis and subvert host immunity. ESAT-6 mediated autophagosome formation and TLR signaling deviation lead to abnormal activation of NF-κB and subsequent erroneous expression of NF-κB-dependent genes. The C-terminal amino acid residues 90-95 in ESAT-6 are essential for the interaction with host. In-depth appreciation of the multiple roles of ESAT-6 upon host can inform improvements for novel vaccines and diagnostic tools for tuberculosis.