Type VI Secretion System

Little is known about the molecular mechanisms of Francisella pathogenesis, but its ability to survive and replicate within macrophages appears intimately linked to its virulence. The Type VI secretion system (T6SS) is the most widely spread bacterial secretion machinery, usually found to be necessary for virulence. In Gram-negative bacteria, there are two categories for the machineries, the first one for those spanning the inner membrane and the outer, the second one for those span the outer membrane only. The secretion system type VI use a one-step mechanism; whish is transported directly from the bacterial cytoplasm into the extracellular space or into a target cell. The type VI secretion system (T6SS) is a complex with the capacity to translocate

These highly conserved substrates share substantial structural resemblance to the tail tube and needle complex of T4 bacteriophages, respectively, which are required to puncture host membrane in the context of phage infection. Structurally, Hcp and VgrG resemble bacteriophage tail and tailspike proteins, respectively. Hcp and VgrGs form a pilus that is displayed on the bacterial surface. Hcp is secreted by all bacteria with a functional T6SS, and has become a reliable indicator of T6SS function even though the gene encoding Hcp is not always found in T6SS clusters. It is conceivable that the Hcp tube forms the conduit of the T6SS through which proteins are transported out of the bacterial cell and into the extracellular space or the cytosol of infected host cells. Thus, it appears that Hcp is a secreted structural T6SS component. VgrG molecules are assigned a dual function, both as membrane-puncturing tips on the end of an Hcp tube and, in the case of evolved VgrGs, as an effector molecule through the activity of C-terminal