Type VI secretion requires a dynamic contractile phage tail-like structure

Department of Microbiology and Immunobiology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nature (Impact Factor: 41.46). 03/2012; 483(7388):182-6. DOI: 10.1038/nature10846
Source: PubMed


Type VI secretion systems are bacterial virulence-associated nanomachines composed of proteins that are evolutionarily related to components of bacteriophage tails. Here we show that protein secretion by the type VI secretion system of Vibrio cholerae requires the action of a dynamic intracellular tubular structure that is structurally and functionally homologous to contractile phage tail sheath. Time-lapse fluorescence light microscopy reveals that sheaths of the type VI secretion system cycle between assembly, quick contraction, disassembly and re-assembly. Whole-cell electron cryotomography further shows that the sheaths appear as long tubular structures in either extended or contracted conformations that are connected to the inner membrane by a distinct basal structure. These data support a model in which the contraction of the type VI secretion system sheath provides the energy needed to translocate proteins out of effector cells and into adjacent target cells.

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    • "It forms an elongated protein complex, which is structurally related to the tail-tube and puncturing device of bacteriophages (Shneider et al., 2013; Zoued et al., 2014). The T6SS is an extremely dynamic contractile nanomachine (Basler et al., 2012; Bönemann et al., 2010; Clemens et al., 2015; Kudryashev et al., 2015) that attacks cells by initially penetrating them with a trimeric protein complex called the VgrG spike. The spike first assembles into a membraneanchored complex formed of an inner tail tube made of Hcp proteins surrounded by an outer sheath composed of VipAand VipB-like proteins (Bönemann et al., 2009). "
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    ABSTRACT: The Gram-negative bacterial type VI Secretion System (T6SS) delivers toxins to kill or inhibit the growth of susceptible bacteria, while others target eukaryotic cells. Deletion of atsR, a negative regulator of virulence factors in B. cenocepacia K56-2, increases T6SS activity. Macrophages infected with a K56-2 ΔatsR mutant display dramatic alterations in their actin cytoskeleton architecture that rely on the T6SS, which is responsible for the inactivation of multiple Rho-family GTPases by an unknown mechanism. We employed a strategy to standardize the bacterial infection of macrophages and densitometrically quantify the T6SS-associated cellular phenotype, which allowed us to characterize the phenotype of systematic deletions of each gene within the T6SS cluster and ten vgrG encoding genes in K56-2 ΔatsR. None of the genes from the T6SS core cluster and the individual vgrGs were directly responsible for the cytoskeletal changes in infected cells. However, a mutant strain with all vgrG genes deleted was unable to cause macrophage alterations. Despite not being able to identify a specific effector protein responsible for the cytoskeletal defects in macrophages, our strategy resulted in the identification of the critical core components and accessory proteins of the T6SS assembly machinery and provides a screening method to detect T6SS effectors targeting the actin cytoskeleton in macrophages by random mutagenesis.
    Microbiology 09/2015; DOI:10.1099/mic.0.000174 · 2.56 Impact Factor
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    • "The appearance of Stacks in the tomogram slices bore a resemblance to the structure of the type 6 secretion system (T6SS). T6SS forms highly dynamic intracellular tubes, which assemble and disassemble in a few seconds at different subcellular locations (Chang et al., 2014; Basler et al., 2012). Moreover, both structures, Stacks and T6SS, are oriented roughly perpendicular to the PM and are located exclusively in the cytosol. "
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    • "High sequence similarities and striking structural parallels between the phage tail structures and bacterial pyocins reveal a clear evolutionary connection between these complex molecular devices (Nakayama et al., 2000). Another phage-like structure found in bacteria including P. aeruginosa is a dynamic bacterial type VI secretion system (T6SS) used for translocation of virulence factors into target cells: the same mechanism the phage uses to transfer its genome to the host (Basler et al., 2012). Moreover, a recent report has shown that phage tail-like structures produced by marine bacterium Pseudoalteromonas luteoviolacea can trigger metamorphosis of a marine tubeworm, providing novel insights into the intricate interaction between phage, bacterium and animal (Shikuma et al., 2014). "
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    ABSTRACT: Complex interactions between bacteriophages and their bacterial hosts play significant roles in shaping the structure of environmental microbial communities, not only by genetic transduction but also by modification of bacterial gene expression patterns. Survival of phages solely depends on their ability to infect their bacterial hosts, most importantly during phage entry. Successful dynamic adaptation of bacteriophages when facing selective pressures, such as host adaptation and resistance, dictates their abundance and diversification. Co-evolution of the phage tail fibers and bacterial receptors determine bacterial host ranges, mechanisms of phage entry, and other infection parameters. This review summarizes the current knowledge about the physical interactions between tailed bacteriophages and bacterial pathogens (e.g., Salmonella enterica and Pseudomonas aeruginosa) and the influences of the phage on host gene expression. Understanding these interactions can offer insights into phage-host dynamics and suggest novel strategies for the design of bacterial pathogen biological controls.
    Frontiers in Microbiology 08/2014; 5:442. DOI:10.3389/fmicb.2014.00442 · 3.99 Impact Factor
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