Type VI secretion system helps find a niche.

Type VI secretion systems (T6SSs) deliver toxins into target cells and thus play a role in bacterial warfare. In this issue of Cell Host & Microbe, Ma et al. (2014) demonstrate that T6SS-dependent attack during interbacterial competition in the host context enables niche colonization by Agrobacterium tumefaciens.

Structure of the VipA/B type VI secretion complex suggests a contraction-state-specific recycling mechanism.

The bacterial type VI secretion system is a multicomponent molecular machine directed against eukaryotic host cells and competing bacteria. An intracellular contractile tubular structure that bears functional homology with bacteriophage tails is pivotal for ejection of pathogenic effectors. Here, we present the 6 Å cryoelectron microscopy structure of the contracted Vibrio cholerae tubule consisting of the proteins VipA and VipB. We localized VipA and VipB in the protomer and identified structural homology between the C-terminal segment of VipB and the tail-sheath protein of T4 phages. We propose that homologous segments in VipB and T4 phages mediate tubule contraction. We show that in type VI secretion, contraction leads to exposure of the ClpV recognition motif, which is embedded in the type VI-specific four-helix-bundle N-domain of VipB. Disaggregation of the tubules by the AAA+ protein ClpV and recycling of the VipA/B subunits are thereby limited to the contracted state.

ClpV recycles VipA/VipB tubules and prevents non-productive tubule formation to ensure efficient type VI protein secretion.

The multicomponent type VI secretion system (T6SS) mediates the transport of effector proteins by puncturing target membranes. T6SSs are suggested to form a contractile nanomachine, functioning similar to the cell-puncturing device of tailed bacteriophages. The T6SS members VipA/VipB form tubular complexes and are predicted to function in analogy to viral tail sheath proteins by providing the energy for secretion via contraction. The ATPase ClpV disassembles VipA/VipB tubules in vitro, but the physiological relevance of tubule disintegration remained unclear. Here, we show that VipA/VipB tubules localize near-perpendicular to the inner membrane of Vibrio cholerae cells and exhibit repetitive cycles of elongation, contraction and disassembly. VipA/VipB tubules are decorated by ClpV in vivo and become static in ΔclpV cells, indicating that ClpV is required for tubule removal. VipA/VipB tubules mislocalize in ΔclpV cells and exhibit a reduced frequency of tubule elongation, indicating that ClpV also suppresses the spontaneous formation of contracted, non-productive VipA/VipB tubules. ClpV activity is restricted to the contracted state of VipA/VipB, allowing formation of functional elongated tubules at a T6SS assembly. Targeting of an unrelated ATPase to VipA/VipB is sufficient to replace ClpV function in vivo, suggesting that ClpV activity is autonomously regulated by VipA/VipB conformation.

Deadly syringes: type VI secretion system activities in pathogenicity and interbacterial competition.

Among specialized bacterial secretion systems, the most widespread is the type VI secretion system (T6SS). This transports effector molecules into target cells in a single, cell-contact dependent step. T6SSs are structurally related to the cell-puncturing device of tailed bacteriophages and predicted to function as contractile injection machineries that perforate eukaryotic and prokaryotic target membranes for effector delivery. Activities of T6SSs can play important roles in virulence by modifying the eukaryotic host cytoskeleton through actin crosslinking. They are also efficient weaponry in interbacterial warfare and provide a fitness advantage by hydrolyzing cell walls of opponent bacteria. The role of T6SSs in interbacterial competition might enable pathogens to outcompete commensal bacteria and facilitate host colonization.