1.C.95 The Pore-forming ESAT-6 Protein (ESAT-6) Family
The ESX-1 secretion system (TC# 9.A.25) plays a critical role in virulence of M. tuberculosis and M. marinum. Virulent M marinum is able to escape from the Mycobacterium-containing vacuole (MCV) into the host cell cytosol, polymerize actin, and spread from cell to cell. ESX-1 plays an essential role in M. marinum escape from the MCV.
Smith et al. (2008) provided evidence that M. marinum induces membrane pores approximately 4.5 nm in diameter, and this activity correlates with ESAT-6 secretion. Purified ESTAT-6, but not the other ESX-1-secreted proteins, is able to cause dose-dependent pore formation in host cell membranes.
M. tuberculosis uses protein secretion systems, named 6 kDa early secretory antigenic target (ESAT6) protein family secretion (ESX) systems to export a set of effector proteins that help the pathogen resist or evade the host immune response (Gröschel et al. 2016). Since the discovery of the esx loci during the M. tuberculosis H37Rv genome project, structural biology, cell biology and evolutionary analyses have been conducted. Gröschel et al. 2016 reviewed roles that these studies have revealed for ESX systems in bacterial survival and pathogenicity during infection with M. tuberculosis. They discuss the diversity of ESX systems that has been described among mycobacteria and selected non-mycobacterial species.
The reaction catalyzed for ESAT-6 is:
molecules (vacuoles) ⇌ molecules (cytoplasm)