Mechanism of ESAT-6 membrane interaction and its roles in pathogenesis of Mycobacterium tuberculosis

•ESAT-6, an essential virulence factor of Mycobacterium tuberculosis, is a pore-forming toxin.•We review the current understanding of ESAT-6 roles in pathogenesis.•We discuss the remaining questions related to ESAT-6 pore-forming activity.

The 6-kDa early secreted antigenic target (ESAT-6; EsxA) of Mycobacterium tuberculosis was first identified as a potent T-cell antigen, and it is now recognized as a pore-forming toxin that is essential for virulence of M. tuberculosis. ESAT-6 is secreted through the ESX-1 secretion system (Type VII) of M. tuberculosis and has been implicated to mediate mycobacterial cytosolic translocation within the host macrophages by rupturing the phagosomal membranes. Recent studies have made significant progresses in understanding of the mechanism of ESAT-6 membrane interaction and its role in M. tuberculosis pathogenesis, but important questions still remain to be answered. Here, we summarize the current progress in study of ESAT-6 membrane interaction and its roles in pathogenesis and discuss some of the key remaining questions for future investigation.