Assembly and Subcellular Localization of Bacterial Type VI Secretion Systems

Abstract

Bacteria need to deliver large molecules out of the cytosol to the extracellular space or even across membranes of neighboring cells to influence their environment, prevent predation, defeat competitors, or communicate. A variety of protein-secretion systems have evolved to make this process highly regulated and efficient. The type VI secretion system (T6SS) is one of the largest dynamic assemblies in gram-negative bacteria and allows for delivery of toxins into both bacterial and eukaryotic cells. The recent progress in structural biology and live-cell imaging shows the T6SS as a long contractile sheath assembled around a rigid tube with associated toxins anchored to a cell envelope by a baseplate and membrane complex. Rapid sheath contraction releases a large amount of energy used to push the tube and toxins through the membranes of neighboring target cells. Because reach of the T6SS is limited, some bacteria dynamically regulate its subcellular localization to precisely aim at their targets and thus increase efficiency of toxin translocation.

Intramolecular chaperone-mediated secretion of an Rhs effector toxin by a type VI secretion system

“…The T6SS plays a critical role in interspecies interaction and during infection by translocating toxic effectors to bacterial and eukaryotic host cells [20][21][22][23] . The needle-like T6SS resembles a contractile bacteriophage-like tail, consisting of a VipA/B outer sheath, an Hcp inner tube, and a transmembrane-baseplate complex 24,25 . The tip of the tube is "sharpened" by a spike complex made of a VgrG trimer and a PAAR protein 26 .…”

Diverse roles of TssA‐like proteins in the assembly of bacterial type VI secretion systems

“…The nanomachine structurally and functionally resembles the contractile tail of bacteriophages and R‐type pyocins (Brackmann et al , ). T6SS biogenesis proceeds in a strictly hierarchical order (Wang et al , ). First, a protein complex spanning both membranes forms (Aschtgen et al , ; Felisberto‐Rodrigues et al , ; Durand et al , ).…”

Integrating signals to drive type VI secretion system killing

“…Indeed, unless resources are limited or cell density is high, it makes little sense to expend resources being highly aggressive (Gonzalez and Mavridou, 2019). Thus, expression of the T6SS is highly regulated in many organisms, presumably to enable expression in defined conditions (Silverman et al ., 2012; Allsopp et al ., 2017; Wang et al ., 2019).…”

“…1) (Silverman et al ., 2012; Allsopp et al ., 2017; Wang et al ., 2019). Many T6SS genes are not expressed well in laboratory conditions; however, a common theme is enhanced expression in the later stages of growth, nutrient availability and upon surface contact (Silverman et al ., 2012; Wang et al ., 2019). Moreover, different bacteria have integrated T6SS genes into a variety of existing regulatory networks enabling expression under beneficial conditions.…”

“…Moreover, different bacteria have integrated T6SS genes into a variety of existing regulatory networks enabling expression under beneficial conditions. Major drivers of the T6SS are: quorum sensing, salinity, osmolality, metal iron availability and stress (Silverman et al ., 2012; Wang et al ., 2019; Crisan and Hammer, 2020). Some of these conditions are sensed by bacteria via two‐component systems and relayed into transcriptional regulators for direct control of T6SS genes.…”