Killing in the name of: T6SS structure and effector diversity

Abstract

The life of bacteria is challenging, to endure bacteria employ a range of mechanisms to optimize their environment, including deploying the type VI secretion system (T6SS). Acting as a bacterial crossbow, this system delivers effectors responsible for subverting host cells, killing competitors and facilitating general secretion to access common goods. Due to its importance, this lethal machine has been evolutionarily maintained, disseminated and specialized to fulfil these vital functions. In fact, T6SS structural clusters are present in over 25 % of Gram-negative bacteria, varying in number from one to six different genetic clusters per organism. Since its discovery in 2006, research on the T6SS has rapidly progressed, yielding remarkable breakthroughs. The identification and characterization of novel components of the T6SS, combined with biochemical and structural studies, have revealed fascinating mechanisms governing its assembly, loading, firing and disassembly processes. Recent findings have also demonstrated the efficacy of this system against fungal and Gram-positive cells, expanding its scope. Ongoing research continues to uncover an extensive and expanding repertoire of T6SS effectors, the genuine mediators of T6SS function. These studies are shedding light on new aspects of the biology of prokaryotic and eukaryotic organisms. This review provides a comprehensive overview of the T6SS, highlighting recent discoveries of its structure and the diversity of its effectors. Additionally, it injects a personal perspective on avenues for future research, aiming to deepen our understanding of this combative system.

T6SS: A Key to Pseudomonas’s Success in Biocontrol?

“…Lastly, we note that although this review primarily delves into various aspects of Pseudomonas T6SSs and places emphasis on the intersection between T6SS and biocontrol applications in this genus, it is also important to note that the versatility of this secretion system extends well beyond this field. Numerous reviews have comprehensively covered these various aspects, containing information from T6SS functioning and regulation to its relevance in various ecological niches [96][97][98][99][100][101][102][103].…”

The Love and Hate Relationship between T5SS and Other Secretion Systems in Bacteria

“…Some are phospholipases that alter the composition of lipid bilayers and cause cell lysis. Contact-independent killing typically involves other secretion systems that secret soluble factors such as bacteriocins and other small antimicrobial molecules that can diffuse through the environment and affect distant cells [ 98 , 99 , 100 ]. Rhs from Dickeya dadantii is an effector secreted by T6SS, which has a conserved central region and variable N- and C-terminal regions [ 101 ].…”

A T6SS in the coral pathogenVibrio coralliilyticussecretes an arsenal of anti-eukaryotic effectors and contributes to virulence

“…The T6SS is a proteinaceous apparatus that is assembled inside the bacterial cell: a sheath structure engulfs an inner tube made of stacked hexameric rings of Hcp proteins, which is capped by a spike comprising a VgrG trimer sharpened by a PAAR repeat-containing protein (hereafter referred to as PAAR) [30]. This tubespike complex is decorated with toxic proteins, called effectors, that mediate the toxic activities of the T6SS [31][32][33]. Contraction of the sheath propels the tube-spike complex out of the cell, providing it with sufficient force to penetrate the membrane of a neighboring cell where effectors are deployed [34].…”

“…Contraction of the sheath propels the tube-spike complex out of the cell, providing it with sufficient force to penetrate the membrane of a neighboring cell where effectors are deployed [34]. Whereas most T6SSs investigated to date mediate interbacterial competitions by delivering antibacterial effectors, a few T6SSs have been shown to target eukaryotes and mediate virulence [33,35,36]. In accordance, although most Vibrio T6SSs play a role in interbacterial competitions [24][25][26][27][28][37][38][39], we and others recently revealed Vibrio T6SSs and effectors that target eukaryotes, and we postulated that they play a role in virulence [22,[40][41][42][43].…”