Structural biology of Type VI secretion systems

CNRS, Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UMR 7255, Institut de Microbiologie de la Méditerranée, Aix-Marseille Université, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
Philosophical Transactions of The Royal Society B Biological Sciences (Impact Factor: 7.06). 04/2012; 367(1592):1102-11. DOI: 10.1098/rstb.2011.0209
Source: PubMed


Type VI secretion systems (T6SSs) are transenvelope complexes specialized in the transport of proteins or domains directly into target cells. These systems are versatile as they can target either eukaryotic host cells and therefore modulate the bacteria-host interaction and pathogenesis or bacterial cells and therefore facilitate access to a specific niche. These molecular machines comprise at least 13 proteins. Although recent years have witnessed advances in the role and function of these secretion systems, little is known about how these complexes assemble in the cell envelope. Interestingly, the current information converges to the idea that T6SSs are composed of two subassemblies, one resembling the contractile bacteriophage tail, whereas the other subunits are embedded in the inner and outer membranes and anchor the bacteriophage-like structure to the cell envelope. In this review, we summarize recent structural information on individual T6SS components emphasizing the fact that T6SSs are composite systems, adapting subunits from various origins.

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    • "The C. jejuni T6SS was found to have pleiotropic effects ranging from virulence, influencing cell adhesion, cytotoxicity towards erythrocytes and colonisation of mice (Lertpiriyapong et al., 2012; Bleumink-Pluym et al., 2013; Harrison et al., 2014). Current structural models of T6SS consist of a bacteriophage-like structure and a cell envelope-spanning membrane-associated assembly that translocates protein effectors into different cell types (Cascales and Cambillau, 2012; Silverman et al., 2012). A loci containing 13 ORFs can be subdivided into three groups; group one genes tssJ, tssL and tssM encode for membrane-associated proteins; group two genes tssB, tssC, tssD (hcp), tssE and tssI (vgrG) encode for proteins with function related to tailed bacteriophage components; group three genes tssA, tssF, tssG, tssH (tagH) and tssK encode for proteins with unknown function (Silverman et al., 2012; Fritsch et al., 2013). "
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    ABSTRACT: Infections from Campylobacter jejuni pose a serious public health problem and are now considered the leading cause of foodborne bacterial gastroenteritis throughout the world. Sequencing of C. jejuni genomes has previously allowed a number of loci to be identified, which encode virulence factors that aid survival and pathogenicity. Recently, a Type VI secretion system (T6SS) consisting of 13 conserved genes was described in C. jejuni strains and recognised to promote pathogenicity and adaptation to the environment. In this study, we determined the presence of this T6SS in 63 Spanish C. jejuni isolates from the food chain and urban effluents using whole-genome sequencing. Our findings demonstrated that nine (14%) strains harboured the 13 ORFs found in prototype strain C. jejuni 108. Further studies will be necessary to determine the prevalence and importance of T6SS-positive C. jejuni strains.
    Zoonoses and Public Health 12/2014; 62(7). DOI:10.1111/zph.12176 · 2.37 Impact Factor
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    • "Bacteroidetes T6SS in Interbacterial Antagonism membrane for function, and so far a T6SS iii -conserved predicted outer membrane-localized protein has not been identified. It is worth noting that TssJ, TssL, and TssM interact stably to form a trans-envelope complex (Cascales and Cambillau, 2012). While it has been postulated that this complex facilitates the passage of bacteriophage-like proteins and effectors out of the recipient cell, there are little experimental data to support this notion. "
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    ABSTRACT: Bacteroidetes are a phylum of Gram-negative bacteria abundant in mammalian-associated polymicrobial communities, where they impact digestion, immunity, and resistance to infection. Despite the extensive competition at high cell density that occurs in these settings, cell contact-dependent mechanisms of interbacterial antagonism, such as the type VI secretion system (T6SS), have not been defined in this group of organisms. Herein we report the bioinformatic and functional characterization of a T6SS-like pathway in diverse Bacteroidetes. Using prominent human gut commensal and soil-associated species, we demonstrate that these systems localize dynamically within the cell, export antibacterial proteins, and target competitor bacteria. The Bacteroidetes system is a distinct pathway with marked differences in gene content and high evolutionary divergence from the canonical T6S pathway. Our findings offer a potential molecular explanation for the abundance of Bacteroidetes in polymicrobial environments, the observed stability of Bacteroidetes in healthy humans, and the barrier presented by the microbiota against pathogens.
    Cell host & microbe 08/2014; 16(2). DOI:10.1016/j.chom.2014.07.007 · 12.33 Impact Factor
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    • "Upon bacteriophage landing onto host cells, the attachment of the fibers induces a switch in the baseplate conformation that will ultimately trigger sheath contraction [67] [74]. One may therefore hypothesize that a signal should be transmitted to the putative T6SS baseplate to initiate TssBC contraction [63]. Several T6SS have been shown to be activated by the TagQRST–PppA–PpkA–FHA phosphorylation-dependent pathway and therefore it is conceivable that this post-translational activating pathway leads to a structural modification of the T6SS baseplate or to membrane component(s) that are linked to it. "
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    ABSTRACT: The Type VI secretion system (T6SS) delivers protein effectors to diverse cell types including prokaryotic and eukaryotic cells, therefore participating in inter-bacterial competition and pathogenesis. The T6SS is constituted of an envelope-spanning complex anchoring a cytoplasmic tubular edifice. This tubular structure is evolutionarily, functionally and structurally related to the tail of contractile phages. It is composed of an inner tube tipped by a spike complex, and engulfed within a sheath-like structure. This structure assembles onto a platform called "baseplate" that is connected to the membrane sub-complex. The T6SS functions as a nano-crossbow: upon contraction of the sheath, the inner tube is propelled towards the target cell, allowing effector delivery. This review focuses on the architecture and biogenesis of this fascinating secretion machine, highlighting recent advances regarding the assembly of the membrane or tail complexes. This article is part of a Special Issue entitled: Protein Trafficking & Secretion.
    Biochimica et Biophysica Acta 03/2014; 1843(8). DOI:10.1016/j.bbamcr.2014.03.018 · 4.66 Impact Factor
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