(A) Baseplate complex forms consisting of TssE, TssJ, TssK, TssL and TssM. Other components not pictured include TssA, TssF, and TssG. In some T6SSs, Fha is an essential part of this complex. TssJ, TssK, TssL and TssM are placed in this drawing based on protein localization and interaction studies (; ), while TssE position is inferred from phage homolog () (B) VgrG, PAAR, and effector proteins are recruited to this complex and assemble into the structure. VgrG interaction with PAAR or effectors likely contributes to the overall stability of the apparatus assembly. Although these components are pictured here as being cytosolic, it is unclear whether there is an opening into the periplasm. (C) Hcp tube polymerizes from VgrG while the VipA/VipB sheath polymerizes around it. (D) Analogous to phage, a conformation change in the sheath structure results in a contraction event that launches the Hcp tube out of the cell and across a target membrane. This contraction event delivers the loaded VgrG-effector “warhead” through the layers of the cell envelope, however it is not known how often penetration into the cytosol occurs, if at all. It is also unknown how much Hcp is lost outside the cell and how much is retained within the cytosol. (E) ClpV uses ATP to remodel the contracted sheath, restoring the pool of available sheath subunits. The now unsheathed Hcp tube disassembles; parts of the tube that not expelled from the cell are recycled within the cytosol. (F) The naked baseplate complex is then ready to be recycled or disassembled, depending on the T6SS and its activation state.