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Zheng J., Tung S.L., and Leung K.Y. Regulation of a Type III and a putative secretion system in Edwardsiella tarda by EsrC is under the control of a two-component system, EsrA-EsrB. Infect Immun 73 (2005) 4127-4137
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Parsons D.A., and Heffron F. sciS, an icmF homolog in Salmonella enterica Serovar Typhimurium, limits intracellular replication and decreases virulence. Infect Immun 73 (2005) 4338-4345
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Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system
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Use of a protozoan model of infection, together with transposon mutagenesis of a non-O1/non-O139 strain of V. cholerae leads to a description of the prototypic T6SS, including details of the secretion of Hcp and VgrG proteins and the involvement of Hcp in secretion of VgrG proteins. This T6SS is shown to mediate virulence of V. cholerae towards both Dictyostelium amoebae and a mammalian macrophage cell line.
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Pukatzki S., Ma A.T., Sturtevant D., Krastins B., Sarracino D., Nelson W.C., Heidelberg J.F., and Mekalanos J.J. Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc Natl Acad Sci U S A 103 (2006) 1528-1533. Use of a protozoan model of infection, together with transposon mutagenesis of a non-O1/non-O139 strain of V. cholerae leads to a description of the prototypic T6SS, including details of the secretion of Hcp and VgrG proteins and the involvement of Hcp in secretion of VgrG proteins. This T6SS is shown to mediate virulence of V. cholerae towards both Dictyostelium amoebae and a mammalian macrophage cell line.
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Pukatzki, S.1
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17
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33744974779
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A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus
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This paper demonstrates a strong link between one of the three T6SSs of P. aeruginosa PAO1 and the pathogenicity of this bacterium towards cystic fibrosis patients. The pattern of transcriptional control by global virulence regulators uncovered by microarray studies suggests a role during chronic infection. Structural studies of P. aeruginosa Hcp1 detailed here indicate that it can self-associate, forming a hexameric ring with a wide lumen consistent with a role in forming a channel to translocate secreted proteins
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Mougous J.D., Cuff M.E., Raunser S., Shen A., Zhou M., Gifford C.A., Goodman A.L., Joachimiak G., Ordonez C.L., Lory S., et al. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312 (2006) 1526-1530. This paper demonstrates a strong link between one of the three T6SSs of P. aeruginosa PAO1 and the pathogenicity of this bacterium towards cystic fibrosis patients. The pattern of transcriptional control by global virulence regulators uncovered by microarray studies suggests a role during chronic infection. Structural studies of P. aeruginosa Hcp1 detailed here indicate that it can self-associate, forming a hexameric ring with a wide lumen consistent with a role in forming a channel to translocate secreted proteins
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Science
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Mougous, J.D.1
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Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes
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Ventre I., Goodman A.L., Vallet-Gely I., Vasseur P., Soscia C., Molin S., Bleves S., Lazdunski A., Lory S., and Filloux A. Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes. Proc Natl Acad Sci U S A 103 (2006) 171-176
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19
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Proteomic and microarray characterization of the AggR regulon identifies a pheU pathogenicity island in enteroaggregative Escherichia coli
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The pheU pathogenicity island carries two T6SS gene clusters, one of which is shown to be transcriptionally regulated by AggR, a global regulator of pathogenicity-related genes. This paper describes secretion of the orphan protein AaiC by the AggR-regulated T6SS and of Hcp, encoded by the non-regulated T6SS and provides a useful review and discussion of the prior literature on T6SS.
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Dudley E.G., Thomson N.R., Parkhill J., Morin N.P., and Nataro J.P. Proteomic and microarray characterization of the AggR regulon identifies a pheU pathogenicity island in enteroaggregative Escherichia coli. Mol Microbiol 61 (2006) 1267-1282. The pheU pathogenicity island carries two T6SS gene clusters, one of which is shown to be transcriptionally regulated by AggR, a global regulator of pathogenicity-related genes. This paper describes secretion of the orphan protein AaiC by the AggR-regulated T6SS and of Hcp, encoded by the non-regulated T6SS and provides a useful review and discussion of the prior literature on T6SS.
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Mol Microbiol
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Dudley, E.G.1
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T: jack of all trades. J Bacteriol 188 (2006) 8272-8282
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Brzuszkiewicz E., Brüggemann H., Liesegang H., Emmerth M., Ölschläger T., Nagy G., Albermann K., Wagner C., Buchrieser C., Emody L., et al. How to become a uropathogen: comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains. Proc Natl Acad Sci U S A 103 (2006) 12879-12884
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22
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Type VI secretion is a major virulence determinant in Burkholderia mallei
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This paper describes an Hcp-secreting T6SS of B. mallei, the causative agent of glanders. Expression of the T6SS genes (along with many other virulence genes) is strongly upregulated by the VirAG two-component system and is essential for virulence in a hamster model of infection. This system has been shown to secrete a homologue of Hcp that is recognised in the horse, human and mouse antibody response to infection. The authors describe a search of available bacterial genomes sequences and their discovery of five additional distinct T6SS clusters that are found in Burkholderia species.
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Schell M.A., Ulrich R.L., Ribot W.J., Brueggemann E.E., Hines H.B., Chen D., Lipscomb L., Kim H.S., Mrázek J., Nierman W.C., et al. Type VI secretion is a major virulence determinant in Burkholderia mallei. Mol Microbiol 64 (2007) 1466-1485. This paper describes an Hcp-secreting T6SS of B. mallei, the causative agent of glanders. Expression of the T6SS genes (along with many other virulence genes) is strongly upregulated by the VirAG two-component system and is essential for virulence in a hamster model of infection. This system has been shown to secrete a homologue of Hcp that is recognised in the horse, human and mouse antibody response to infection. The authors describe a search of available bacterial genomes sequences and their discovery of five additional distinct T6SS clusters that are found in Burkholderia species.
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Mol Microbiol
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Schell, M.A.1
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23
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Dissection of a type VI secretion system in Edwardsiella tarda
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This important paper includes details of a systematic mutagenesis of all genes in a T6SS cluster and the effects that these mutations have on type VI secretion. This has allowed the definition of a core set of T6SS proteins required for secretion and also identification of two novel secreted proteins (EvpI and EvpP). The authors have also begun to catalogue the protein-protein interactions involved in assembly of the secretion system.
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Zheng J., and Leung K.Y. Dissection of a type VI secretion system in Edwardsiella tarda. Mol Microbiol 66 (2007) 1192-1206. This important paper includes details of a systematic mutagenesis of all genes in a T6SS cluster and the effects that these mutations have on type VI secretion. This has allowed the definition of a core set of T6SS proteins required for secretion and also identification of two novel secreted proteins (EvpI and EvpP). The authors have also begun to catalogue the protein-protein interactions involved in assembly of the secretion system.
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Mol Microbiol
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Zheng, J.1
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Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin
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Bioinformatic analysis allowed the prediction of a trimeric complex, homologous to the tail spike of phage T4, between the three secreted VgrG proteins and this prediction is supported by immunoprecipitation data. The authors experimentally demonstrate an effector role for one of these proteins (the VgrG-1 protein is translocated into macrophage cells where it has an actin crosslinking function), allowing them to suggest multiple functions for the VgrG complex. VgrG proteins may have a variable C-terminal domain; this domain of V. cholerae VgrG-1 is homologous to the actin crosslinking domain of the RtxA toxin [46] and VgrG homologues from other pathogenic bacteria possess domains that resemble known virulence proteins.
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Pukatzki S., Ma A.T., Revel A.T., Sturtevant D., and Mekalanos J.J. Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin. Proc Natl Acad Sci U S A 104 (2007) 15508-15513. Bioinformatic analysis allowed the prediction of a trimeric complex, homologous to the tail spike of phage T4, between the three secreted VgrG proteins and this prediction is supported by immunoprecipitation data. The authors experimentally demonstrate an effector role for one of these proteins (the VgrG-1 protein is translocated into macrophage cells where it has an actin crosslinking function), allowing them to suggest multiple functions for the VgrG complex. VgrG proteins may have a variable C-terminal domain; this domain of V. cholerae VgrG-1 is homologous to the actin crosslinking domain of the RtxA toxin [46] and VgrG homologues from other pathogenic bacteria possess domains that resemble known virulence proteins.
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Proc Natl Acad Sci U S A
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In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages
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The six T6SS clusters found in B. pseudomallei 10 274 are described here and one of these is shown to be potentially involved in intramacrophage growth.
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Shalom G., Shaw J.G., and Thomas M.S. In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages. Microbiology 153 (2007) 2689-2699. The six T6SS clusters found in B. pseudomallei 10 274 are described here and one of these is shown to be potentially involved in intramacrophage growth.
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A novel mechanism for regulation of secretion is identified that hinges on the balance between phosphorylation and dephosphorylation of a specific threonine residue. This is achieved by the serine-threonine phosphorylase/kinase pair PpkA/PppA acting on the FHA domain protein Fha1, which acts as a core scaffolding protein for the system, recruiting the ClpV protein to the T6SS assembly via an unknown mechanism.
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Mougous J.D., Gifford C.A., Ramsdell T.L., and Mekalanos J.J. Threonine phosphorylation post-translationally regulates protein secretion in Pseudomonas aeruginosa. Nat Cell Biol (2007) 9. A novel mechanism for regulation of secretion is identified that hinges on the balance between phosphorylation and dephosphorylation of a specific threonine residue. This is achieved by the serine-threonine phosphorylase/kinase pair PpkA/PppA acting on the FHA domain protein Fha1, which acts as a core scaffolding protein for the system, recruiting the ClpV protein to the T6SS assembly via an unknown mechanism.
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Nat Cell Biol
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Mougous, J.D.1
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Kulasekara H.D., and Miller S.I. Threonine phosphorylation times bacterial secretion. Nat Cell Biol 9 (2007) 734-736
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Johnson D.L., and Mahony J.B. Chlamydophila pneumoniae PknD exhibits dual amino acid specificity and phosphorylates Cpn0712, a putative type III secretion YscD homolog. J Bacteriol 189 (2007) 7549-7555
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Zusman T., Feldman M., Halperin E., and Segal G. Characterization of the icmH and icmF genes required for Legionella pneumophila intracellular growth, genes that are present in many bacteria associated with eukaryotic cells. Infect Immun 72 (2004) 3398-3409
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Genetic and biochemical analysis of Salmonella typhimurium FliI, a flagellar protein related to the catalytic subunit of the F0F1 ATPase and to virulence proteins of mammalian and plant pathogens
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Weibezahn J., Bukau B., and Mogk A. Unscrambling an egg: protein disaggregation by AAA+ proteins. Microb Cell Fact 3 (2004) 1
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The Francisella pathogenicity island protein IgIA localizes to the bacterial cytoplasm and is needed for intracellular growth
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The F. tularensis homologues of T6SS proteins DUF877 (IglA) and DUF770 (IglB) proteins were shown to interact (co-immunoprecipitate) and the stability of IglA, a soluble cytoplasmic protein, was found to be dependent on IglB. It is suggested that a complex of these two proteins may have a role in chaperoning secreted proteins.
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