Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin

TLDR

Type VI secretion systems are widespread in Gram‑negative pathogens and in Vibrio cholerae secrete VgrG‑1, VgrG‑2, and VgrG‑3 proteins that are predicted to assemble into a trimeric complex resembling phage tail spikes. The authors propose that the VgrG components assemble a phage‑tail‑spike‑like puncturing device to deliver effector domains into host cell membranes. They suggest that the VgrG proteins form a membrane‑penetrating complex analogous to phage tail spikes, enabling translocation of effectors across target cell membranes. VgrG‑1 covalently cross‑links actin in vitro, is translocated into macrophages by a T6SS‑dependent mechanism, and interacts with VgrG‑2 and VgrG‑3, supporting the existence of a trimeric complex.

Abstract

Genes encoding type VI secretion systems (T6SS) are widely distributed in pathogenic Gram-negative bacterial species. In Vibrio cholerae , T6SS have been found to secrete three related proteins extracellularly, VgrG-1, VgrG-2, and VgrG-3. VgrG-1 can covalently cross-link actin in vitro , and this activity was used to demonstrate that V. cholerae can translocate VgrG-1 into macrophages by a T6SS-dependent mechanism. Protein structure search algorithms predict that VgrG-related proteins likely assemble into a trimeric complex that is analogous to that formed by the two trimeric proteins gp27 and gp5 that make up the baseplate “tail spike” of Escherichia coli bacteriophage T4. VgrG-1 was shown to interact with itself, VgrG-2, and VgrG-3, suggesting that such a complex does form. Because the phage tail spike protein complex acts as a membrane-penetrating structure as well as a conduit for the passage of DNA into phage-infected cells, we propose that the VgrG components of the T6SS apparatus may assemble a “cell-puncturing device” analogous to phage tail spikes to deliver effector protein domains through membranes of target host cells.