The ESX-1 (ESAT-6 system-1) secretion system plays a conserved role in the virulence of diverse mycobacterial pathogens including the human pathogen， and an environmental mycobacterial species. The ESX-1 system promotes the secretion of protein virulence factors to the extra-cytoplasmic environment. The secretion of these proteins triggers the host response by lysing the phagosome during macrophage infection. Using proteomic analyses of the secretome in the presence and absence of a functional ESX-1 system， we and others have hypothesized that MMAR_2894， a PE family protein， is a potential ESX-1 substrate in We used genetic and quantitative proteomic approaches to determine if MMAR_2894 is secreted ... More
The ESX-1 (ESAT-6 system-1) secretion system plays a conserved role in the virulence of diverse mycobacterial pathogens including the human pathogen， and an environmental mycobacterial species. The ESX-1 system promotes the secretion of protein virulence factors to the extra-cytoplasmic environment. The secretion of these proteins triggers the host response by lysing the phagosome during macrophage infection. Using proteomic analyses of the secretome in the presence and absence of a functional ESX-1 system， we and others have hypothesized that MMAR_2894， a PE family protein， is a potential ESX-1 substrate in We used genetic and quantitative proteomic approaches to determine if MMAR_2894 is secreted by the ESX-1 system， and we defined the requirement of in ESX-1 mediated secretion and virulence. We show that MMAR_2894 is secreted by the ESX-1 system in and is itself required for the optimal secretion of the known ESX-1 substrates in Moreover， we found that MMAR_2894 was differentially required for hemolysis and cytolysis of macrophages， two lytic activities ascribed to the ESX-1 system. Both the cause of human TB， and a pathogen of ectotherms， use the ESX-1 secretion system to cause disease. There are many established similarities between the ESX-1 systems in and in Yet， the two bacteria infect different hosts， hinting at species specific functions of the ESX-1 system. Our findings demonstrate that MMAR_2894 is a PE protein secreted by the ESX-1 system of We show that MMAR_2894 is required for the optimal secretion of mycobacterial proteins required for disease. Because the gene is not conserved in our findings demonstrate that MMAR_2894 may contribute to a species specific function of the ESX-1 system in providing new insight into how the and systems differ.
