Type VI secretion system
The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport effectors from the interior (cytoplasm or cytosol) of a bacterial cell across the cellular envelope into an adjacent target cell. While often reported that the T6SS was discovered in 2006 by researchers studying the causative agent of cholera, Vibrio cholerae, the first study demonstrating that T6SS genes encode a protein export apparatus was actually published in 2004, in a study of protein secretion by the fish pathogen Edwardsiella tarda. Since then, it is estimated that at least a quarter of all pathogenic and non-pathogenic proteobacterial genomes encode for a T6SS, including pathogens of animals, plants, and humans, as well as soil, environmental or marine bacteria. Genes encoding for the T6SSs are commonly found chromosomally, but can also be harboured in mobile genetic elements and on plasmids mediating their transfer and increase in genetic diversity. While most of the early studies of Type VI secretion focused on its role in the pathogenesis of higher organisms, it is now known to function primarily in interbacterial antagonism. Structure and mechanism The T6SS is thought to resemble an inverted phage extending outward from the bacterial cell surface. It consists of 14 proteins that assemble into three sub-complexes: a phage tail-like tubule, a phage baseplate-like structure, and cell-envelope spanning membrane complex. These three subcomplexes work together to transport proteins across the bacterial cell envelope and into a target cell through a contractile mechanism Phage tail-like The phage tail-like component of the T6SS is a dynamic tubular structure that undergoes cycles of assembly and disassembly. It can be up to 600 nm long, and has been visualized extending across the bacterial cytoplasm in electron micrographs. The tubules consist of repeating units of the proteins TssA and TssB (VipA/VipB) arranged as a sheath around a tube built from stacked hexameric rings of the haemolysin co-regulated protein (Hcp). At the tip of the Hcp tube sits a trimer of the phage tail spike-like protein VgrG, which is in turn capped by a pointed PAAR domain-containing protein. Contraction of the sheath is thought to propel the Hcp tube, VgrG and associated substrates outside of the bacterial cell, where the VgrG/PAAR spike facilitates penetration of the membrane of a neighboring cell. The tubule structure is dismantled through the action of the ATP-degrading protein ClpV, which sits at the tubule base. Baseplate The phage tail-like tubule of the T6SS assembles on a structure analogous to bacteriophage baseplates. It consists of the proteins TssE, TssF, TssG, and TssK. The baseplate and phage tail-like complex interact in the bacterial cytoplasm, and then are recruited to the cell envelope by the membrane complex. Membrane The T6SS membrane complex is responsible for anchoring the apparatus to the cellular membrane, and provides the channel through which substrates are propelled by the contraction of the phage tail-like tubule. This large (1.7 md) complex is formed from 10 interacting units of a heterotrimer containing TssJ, TssM and TssL.