Countering the effector functions of ESAT-6 protein in Mycobacterium tuberculosis: strategies for developing antimycobacterial therapeutics.

Tuberculosis is an infectious disease primarily caused by the bacterium Mycobacterium tuberculosis. This bacterium infects about 10 million and kills about 1.6 million people annually. M. tuberculosis infects macrophages and manipulates its defense functions to safely replicate inside it. Sequence comparison between an attenuated Mycobacterium bovis bacille Calmette-Guérin (BCG) strain and M. tuberculosis identified a region of difference 1 (RD1) which encodes highly antigenic proteins, such as early secretory antigenic target-6 (ESAT-6) and 10-kDa culture filtrate protein (CFP-10), and proteins that make up the ATP-dependent secretory apparatus. Various studies suggest that the ESAT-6 protein counteracts various innate and adaptive immune functions of the host and is involved in regulating mycobacterial virulence. This review focuses on how ESAT-6 manipulates host immune responses that are critical for the survival and virulence of M. tuberculosis. We also discuss the possible therapeutic management of tuberculosis by targeting ESAT-6.