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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Available from: Christian Cambillau
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    • "By motif and profile HMM analysis, we identified presumed functional equivalents of nine of these 13 Proteobacterial core proteins in gut Bacteroidales T6SS loci; however, genes encoding identifiable TssA, TssJ, TssL and TssM proteins were not detected. The function of TssA is currently unknown; however, TssJ, TssL, and TssM likely form a transenvelope complex that anchors the phage tail structure[27,28]. There are five proteins of unknown function encoded within the Bacteroidales T6SS of all three genetic architectures. "
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    ABSTRACT: Type VI secretion systems (T6SSs) are contact-dependent antagonistic systems employed by Gram negative bacteria to intoxicate other bacteria or eukaryotic cells. T6SSs were recently discovered in a few Bacteroidetes strains, thereby extending the presence of these systems beyond Proteobacteria. The present study was designed to analyze in a global nature the diversity, abundance, and properties of T6SSs in the Bacteroidales, the most predominant Gram negative bacterial order of the human gut. By performing extensive bioinformatics analyses and creating hidden Markov models for Bacteroidales Tss proteins, we identified 130 T6SS loci in 205 human gut Bacteroidales genomes. Of the 13 core T6SS proteins of Proteobacteria, human gut Bacteroidales T6SS loci encode orthologs of nine, and an additional five other core proteins not present in Proteobacterial T6SSs. The Bacteroidales T6SS loci segregate into three distinct genetic architectures with extensive DNA identity between loci of a given genetic architecture. We found that divergent DNA regions of a genetic architecture encode numerous types of effector and immunity proteins and likely include new classes of these proteins. TheT6SS loci of genetic architecture 1 are contained on highly similar integrative conjugative elements (ICEs), as are the T6SS loci of genetic architecture 2, whereas the T6SS loci of genetic architecture 3 are not and are confined to Bacteroides fragilis. Using collections of co-resident Bacteroidales strains from human subjects, we provide evidence for the transfer of genetic architecture 1 T6SS loci among co-resident Bacteroidales species in the human gut. However, we also found that established ecosystems can harbor strains with distinct T6SS of all genetic architectures. This is the first study to comprehensively analyze of the presence and diversity of T6SS loci within an order of bacteria and to analyze T6SSs of bacteria from a natural community. These studies demonstrate that more than half of our gut Bacteroidales, equivalent to about ¼ of the bacteria of this ecosystem, encode T6SSs. The data reveal several novel properties of these systems and suggest that antagonism between or distributed defense among these abundant intestinal bacteria may be common in established human gut communities.
    Full-text · Article · Dec 2016 · BMC Genomics
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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.
    Full-text · Article · Dec 2014 · Zoonoses and Public Health
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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.
    Full-text · Article · Aug 2014 · Cell host & microbe
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