1887

Abstract

serovars cause severe disease in humans, such as gastroenteritis and typhoid fever. The bacteria are able to invade and replicate within host cells, including epithelial cells and macrophages. Pathogenesis of is facilitated by a type III secretion system (T3SS) encoded by genes of pathogenicity island 2 (SPI-2). Intracellular replication occurs in a specialized membrane compartment, the -containing vacuole (SCV), and depends on translocation of approximately 30 effector proteins via the SPI-2 T3SS into the host endomembrane system and cytoplasm. In this review we discuss the many different functions of these effectors, which range from maintaining the integrity of the SCV and its juxtanuclear location, to interference with the host cytoskeleton and immune signalling.

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2012-05-01
2020-09-26
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References

  1. Abrahams G. L., Müller P., Hensel M.. ( 2006;). Functional dissection of SseF, a type III effector protein involved in positioning the Salmonella-containing vacuole. Traffic7:950–965 [CrossRef][PubMed]
    [Google Scholar]
  2. Arena E. T., Auweter S. D., Antunes L. C. M., Vogl A. W., Han J., Guttman J. A., Croxen M. A., Menendez A., Covey S. D.. & other authors ( 2011;). The deubiquitinase activity of the Salmonella pathogenicity island 2 effector, SseL, prevents accumulation of cellular lipid droplets. Infect Immun79:4392–4400 [CrossRef][PubMed]
    [Google Scholar]
  3. Aussel L., Zhao W., Hébrard M., Guilhon A. A., Viala J. P., Henri S., Chasson L., Gorvel J. P., Barras F., Méresse S.. ( 2011;). Salmonella detoxifying enzymes are sufficient to cope with the host oxidative burst. Mol Microbiol80:628–640 [CrossRef][PubMed]
    [Google Scholar]
  4. Auweter S. D., Bhavsar A. P., de Hoog C. L., Li Y., Chan Y. A., van der Heijden J., Lowden M. J., Coombes B. K., Rogers L. D.. & other authors ( 2011;). Quantitative mass spectrometry catalogues Salmonella pathogenicity island-2 effectors and identifies their cognate host binding partners. J Biol Chem286:24023–24035 [CrossRef][PubMed]
    [Google Scholar]
  5. Bernal-Bayard J., Ramos-Morales F.. ( 2009;). Salmonella type III secretion effector SlrP is an E3 ubiquitin ligase for mammalian thioredoxin. J Biol Chem284:27587–27595 [CrossRef][PubMed]
    [Google Scholar]
  6. Bernal-Bayard J., Cardenal-Muñoz E., Ramos-Morales F.. ( 2010;). The Salmonella type III secretion effector, Salmonella leucine-rich repeat protein (SlrP), targets the human chaperone ERdj3. J Biol Chem285:16360–16368 [CrossRef][PubMed]
    [Google Scholar]
  7. Beuzón C. R., Banks G., Deiwick J., Hensel M., Holden D. W.. ( 1999;). pH-dependent secretion of SseB, a product of the SPI-2 type III secretion system of Salmonella typhimurium . Mol Microbiol33:806–816 [CrossRef][PubMed]
    [Google Scholar]
  8. Beuzón C. R., Méresse S., Unsworth K. E., Ruíz-Albert J., Garvis S., Waterman S. R., Ryder T. A., Boucrot E., Holden D. W.. ( 2000;). Salmonella maintains the integrity of its intracellular vacuole through the action of SifA. EMBO J19:3235–3249 [CrossRef][PubMed]
    [Google Scholar]
  9. Beuzón C. R., Salcedo S. P., Holden D. W.. ( 2002;). Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines. Microbiology148:2705–2715[PubMed]
    [Google Scholar]
  10. Birmingham C. L., Jiang X., Ohlson M. B., Miller S. I., Brumell J. H.. ( 2005;). Salmonella-induced filament formation is a dynamic phenotype induced by rapidly replicating Salmonella enterica serovar Typhimurium in epithelial cells. Infect Immun73:1204–1208 [CrossRef][PubMed]
    [Google Scholar]
  11. Boucrot E., Beuzón C. R., Holden D. W., Gorvel J. P., Méresse S.. ( 2003;). Salmonella typhimurium SifA effector protein requires its membrane-anchoring C-terminal hexapeptide for its biological function. J Biol Chem278:14196–14202 [CrossRef][PubMed]
    [Google Scholar]
  12. Boucrot E., Henry T., Borg J.-P., Gorvel J.-P., Méresse S.. ( 2005;). The intracellular fate of Salmonella depends on the recruitment of kinesin. Science308:1174–1178 [CrossRef][PubMed]
    [Google Scholar]
  13. Bowe F., Lipps C. J., Tsolis R. M., Groisman E., Heffron F., Kusters J. G.. ( 1998;). At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice. Infect Immun66:3372–3377[PubMed]
    [Google Scholar]
  14. Brown N. F., Coombes B. K., Bishop J. L., Wickham M. E., Lowden M. J., Gal-Mor O., Goode D. L., Boyle E. C., Sanderson K. L., Finlay B. B.. ( 2011;). Salmonella phage ST64B encodes a member of the SseK/NleB effector family. PLoS ONE6:e17824 [CrossRef][PubMed]
    [Google Scholar]
  15. Browne S. H., Lesnick M. L., Guiney D. G.. ( 2002;). Genetic requirements for Salmonella-induced cytopathology in human monocyte-derived macrophages. Infect Immun70:7126–7135 [CrossRef][PubMed]
    [Google Scholar]
  16. Browne S. H., Hasegawa P., Okamoto S., Fierer J., Guiney D. G.. ( 2008;). Identification of Salmonella SPI-2 secretion system components required for SpvB-mediated cytotoxicity in macrophages and virulence in mice. FEMS Immunol Med Microbiol52:194–201 [CrossRef][PubMed]
    [Google Scholar]
  17. Brumell J. H., Rosenberger C. M., Gotto G. T., Marcus S. L., Finlay B. B.. ( 2001;). SifA permits survival and replication of Salmonella typhimurium in murine macrophages. Cell Microbiol3:75–84 [CrossRef][PubMed]
    [Google Scholar]
  18. Brumell J. H., Kujat-Choy S., Brown N. F., Vallance B. A., Knodler L. A., Finlay B. B.. ( 2003;). SopD2 is a novel type III secreted effector of Salmonella typhimurium that targets late endocytic compartments upon delivery into host cells. Traffic4:36–48 [CrossRef][PubMed]
    [Google Scholar]
  19. Bruno V. M., Hannemann S., Lara-Tejero M., Flavell R. A., Kleinstein S. H., Galán J. E.. ( 2009;). Salmonella Typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells. PLoS Pathog5:e1000538 [CrossRef][PubMed]
    [Google Scholar]
  20. Carter P. B., Collins F. M.. ( 1974;). The route of enteric infection in normal mice. J Exp Med139:1189–1203 [CrossRef][PubMed]
    [Google Scholar]
  21. Castle A., Castle D.. ( 2005;). Ubiquitously expressed secretory carrier membrane proteins (SCAMPs) 1–4 mark different pathways and exhibit limited constitutive trafficking to and from the cell surface. J Cell Sci118:3769–3780 [CrossRef][PubMed]
    [Google Scholar]
  22. Catron D. M., Sylvester M. D., Lange Y., Kadekoppala M., Jones B. D., Monack D. M., Falkow S., Haldar K.. ( 2002;). The Salmonella-containing vacuole is a major site of intracellular cholesterol accumulation and recruits the GPI-anchored protein CD55. Cell Microbiol4:315–328 [CrossRef][PubMed]
    [Google Scholar]
  23. Chakravortty D., Hansen-Wester I., Hensel M.. ( 2002;). Salmonella pathogenicity island 2 mediates protection of intracellular Salmonella from reactive nitrogen intermediates. J Exp Med195:1155–1166 [CrossRef][PubMed]
    [Google Scholar]
  24. Chakravortty D., Rohde M., Jäger L., Deiwick J., Hensel M.. ( 2005;). Formation of a novel surface structure encoded by Salmonella pathogenicity island 2. EMBO J24:2043–2052 [CrossRef][PubMed]
    [Google Scholar]
  25. Chen H., Yang J., Low P. S., Cheng J.-X.. ( 2008;). Cholesterol level regulates endosome motility via Rab proteins. Biophys J94:1508–1520 [CrossRef][PubMed]
    [Google Scholar]
  26. Christen M., Coye L. H., Hontz J. S., LaRock D. L., Pfuetzner R. A., Megha, Miller S. I.. ( 2009;). Activation of a bacterial virulence protein by the GTPase RhoA. Sci Signal2:ra71 [CrossRef][PubMed]
    [Google Scholar]
  27. Cirillo D. M., Valdivia R. H., Monack D. M., Falkow S.. ( 1998;). Macrophage-dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival. Mol Microbiol30:175–188 [CrossRef][PubMed]
    [Google Scholar]
  28. Coombes B. K., Wickham M. E., Brown N. F., Lemire S., Bossi L., Hsiao W. W. L., Brinkman F. S. L., Finlay B. B.. ( 2005;). Genetic and molecular analysis of GogB, a phage-encoded type III-secreted substrate in Salmonella enterica serovar Typhimurium with autonomous expression from its associated phage. J Mol Biol348:817–830 [CrossRef][PubMed]
    [Google Scholar]
  29. Coombes B. K., Lowden M. J., Bishop J. L., Wickham M. E., Brown N. F., Duong N., Osborne S., Gal-Mor O., Finlay B. B.. ( 2007;). SseL is a Salmonella-specific translocated effector integrated into the SsrB-controlled Salmonella pathogenicity island 2 type III secretion system. Infect Immun75:574–580 [CrossRef][PubMed]
    [Google Scholar]
  30. Crump J. A., Luby S. P., Mintz E. D.. ( 2004;). The global burden of typhoid fever. Bull World Health Organ82:346–353[PubMed]
    [Google Scholar]
  31. Deiwick J., Salcedo S. P., Boucrot E., Gilliland S. M., Henry T., Petermann N., Waterman S. R., Gorvel J. P., Holden D. W., Méresse S.. ( 2006;). The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche. Infect Immun74:6965–6972 [CrossRef][PubMed]
    [Google Scholar]
  32. Diacovich L., Dumont A., Lafitte D., Soprano E., Guilhon A.-A., Bignon C., Gorvel J.-P., Bourne Y., Méresse S.. ( 2009;). Interaction between the SifA virulence factor and its host target SKIP is essential for Salmonella pathogenesis. J Biol Chem284:33151–33160 [CrossRef][PubMed]
    [Google Scholar]
  33. Dumont A., Boucrot E., Drevensek S., Daire V., Gorvel J.-P., Poüs C., Holden D. W., Méresse S.. ( 2010;). SKIP, the host target of the Salmonella virulence factor SifA, promotes kinesin-1-dependent vacuolar membrane exchanges. Traffic11:899–911 [CrossRef][PubMed]
    [Google Scholar]
  34. Eulalio A., Fröhlich K. S., Mano M., Giacca M., Vogel J.. ( 2011;). A candidate approach implicates the secreted Salmonella effector protein SpvB in P-body disassembly. PLoS ONE6:e17296 [CrossRef][PubMed]
    [Google Scholar]
  35. Fang S., Weissman A. M.. ( 2004;). Ubiquitin-proteasome system. Cell Mol Life Sci61:1546–1561 [CrossRef][PubMed]
    [Google Scholar]
  36. Feng X., Walthers D., Oropeza R., Kenney L. J.. ( 2004;). The response regulator SsrB activates transcription and binds to a region overlapping OmpR binding sites at Salmonella pathogenicity island 2. Mol Microbiol54:823–835 [CrossRef][PubMed]
    [Google Scholar]
  37. Fields P. I., Swanson R. V., Haidaris C. G., Heffron F.. ( 1986;). Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A83:5189–5193 [CrossRef][PubMed]
    [Google Scholar]
  38. Figueroa-Bossi N., Uzzau S., Maloriol D., Bossi L.. ( 2001;). Variable assortment of prophages provides a transferable repertoire of pathogenic determinants in Salmonella . Mol Microbiol39:260–272 [CrossRef][PubMed]
    [Google Scholar]
  39. Forest C. G., Ferraro E., Sabbagh S. C., Daigle F.. ( 2010;). Intracellular survival of Salmonella enterica serovar Typhi in human macrophages is independent of Salmonella pathogenicity island (SPI)-2. Microbiology156:3689–3698 [CrossRef][PubMed]
    [Google Scholar]
  40. Freeman J. A., Rappl C., Kuhle V., Hensel M., Miller S. I.. ( 2002;). SpiC is required for translocation of Salmonella pathogenicity island 2 effectors and secretion of translocon proteins SseB and SseC. J Bacteriol184:4971–4980 [CrossRef][PubMed]
    [Google Scholar]
  41. Freeman J. A., Ohl M. E., Miller S. I.. ( 2003;). The Salmonella enterica serovar Typhimurium translocated effectors SseJ and SifB are targeted to the Salmonella-containing vacuole. Infect Immun71:418–427 [CrossRef][PubMed]
    [Google Scholar]
  42. Galán J. E.. ( 2001;). Salmonella interactions with host cells: type III secretion at work. Annu Rev Cell Dev Biol17:53–86 [CrossRef][PubMed]
    [Google Scholar]
  43. Galyov E. E., Wood M. W., Rosqvist R., Mullan P. B., Watson P. R., Hedges S., Wallis T. S.. ( 1997;). A secreted effector protein of Salmonella dublin is translocated into eukaryotic cells and mediates inflammation and fluid secretion in infected ileal mucosa. Mol Microbiol25:903–912 [CrossRef][PubMed]
    [Google Scholar]
  44. Garcia-del Portillo F., Zwick M. B., Leung K. Y., Finlay B. B.. ( 1993;). Salmonella induces the formation of filamentous structures containing lysosomal membrane glycoproteins in epithelial cells. Proc Natl Acad Sci U S A90:10544–10548 [CrossRef][PubMed]
    [Google Scholar]
  45. Garmendia J., Beuzón C. R., Ruiz-Albert J., Holden D. W.. ( 2003;). The roles of SsrA–SsrB and OmpR–EnvZ in the regulation of genes encoding the Salmonella typhimurium SPI-2 type III secretion system. Microbiology149:2385–2396 [CrossRef][PubMed]
    [Google Scholar]
  46. Geddes K., Worley M., Niemann G., Heffron F.. ( 2005;). Identification of new secreted effectors in Salmonella enterica serovar Typhimurium. Infect Immun73:6260–6271 [CrossRef][PubMed]
    [Google Scholar]
  47. Gotoh Y., Oishi K., Shibata H., Yamagiwa A., Isagawa T., Nishimura T., Goyama E., Takahashi M., Mukai H., Ono Y.. ( 2004;). Protein kinase PKN1 associates with TRAF2 and is involved in TRAF2-NF-κB signaling pathway. Biochem Biophys Res Commun314:688–694 [CrossRef][PubMed]
    [Google Scholar]
  48. Guignot J., Caron E., Beuzón C. R., Bucci C., Kagan J., Roy C., Holden D. W.. ( 2004;). Microtubule motors control membrane dynamics of Salmonella-containing vacuoles. J Cell Sci117:1033–1045 [CrossRef][PubMed]
    [Google Scholar]
  49. Gulig P. A., Doyle T. J.. ( 1993;). The Salmonella typhimurium virulence plasmid increases the growth rate of salmonellae in mice. Infect Immun61:504–511[PubMed]
    [Google Scholar]
  50. Gulig P. A., Danbara H., Guiney D. G., Lax A. J., Norel F., Rhen M.. ( 1993;). Molecular analysis of spv virulence genes of the Salmonella virulence plasmids. Mol Microbiol7:825–830 [CrossRef][PubMed]
    [Google Scholar]
  51. Haneda T., Ishii Y., Shimizu H., Ohshima K., Iida N., Danbara H., Okada N.. ( 2012;). Salmonella type III effector SpvC, a phosphothreonine lyase, contributes to reduction in inflammatory response during intestinal phase of infection. Cell Microbiol [CrossRef][PubMed]
    [Google Scholar]
  52. Hansen-Wester I., Stecher B., Hensel M.. ( 2002;). Type III secretion of Salmonella enterica serovar Typhimurium translocated effectors and SseFG. Infect Immun70:1403–1409 [CrossRef][PubMed]
    [Google Scholar]
  53. Haraga A., Miller S. I.. ( 2003;). A Salmonella enterica serovar Typhimurium translocated leucine-rich repeat effector protein inhibits NF-κB-dependent gene expression. Infect Immun71:4052–4058 [CrossRef][PubMed]
    [Google Scholar]
  54. Haraga A., Miller S. I.. ( 2006;). A Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1. Cell Microbiol8:837–846 [CrossRef][PubMed]
    [Google Scholar]
  55. Harrison R. E., Brumell J. H., Khandani A., Bucci C., Scott C. C., Jiang X., Finlay B. B., Grinstein S.. ( 2004;). Salmonella impairs RILP recruitment to Rab7 during maturation of invasion vacuoles. Mol Biol Cell15:3146–3154 [CrossRef][PubMed]
    [Google Scholar]
  56. Helaine S., Thompson J. A., Watson K. G., Liu M., Boyle C., Holden D. W.. ( 2010;). Dynamics of intracellular bacterial replication at the single cell level. Proc Natl Acad Sci U S A107:3746–3751 [CrossRef][PubMed]
    [Google Scholar]
  57. Henry T., Couillault C., Rockenfeller P., Boucrot E., Dumont A., Schroeder N., Hermant A., Knodler L. A., Lecine P.. & other authors ( 2006;). The Salmonella effector protein PipB2 is a linker for kinesin-1. Proc Natl Acad Sci U S A103:13497–13502 [CrossRef][PubMed]
    [Google Scholar]
  58. Hensel M., Shea J. E., Gleeson C., Jones M. D., Dalton E., Holden D. W.. ( 1995;). Simultaneous identification of bacterial virulence genes by negative selection. Science269:400–403 [CrossRef][PubMed]
    [Google Scholar]
  59. Hensel M., Shea J. E., Bäumler A. J., Gleeson C., Blattner F., Holden D. W.. ( 1997;). Analysis of the boundaries of Salmonella pathogenicity island 2 and the corresponding chromosomal region of Escherichia coli K-12. J Bacteriol179:1105–1111[PubMed]
    [Google Scholar]
  60. Hensel M., Shea J. E., Waterman S. R., Mundy R., Nikolaus T., Banks G., Vazquez-Torres A., Gleeson C., Fang F. C., Holden D. W.. ( 1998;). Genes encoding putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2 are required for bacterial virulence and proliferation in macrophages. Mol Microbiol30:163–174 [CrossRef][PubMed]
    [Google Scholar]
  61. Hindle Z., Chatfield S. N., Phillimore J., Bentley M., Johnson J., Cosgrove C. A., Ghaem-Maghami M., Sexton A., Khan M.. & other authors ( 2002;). Characterization of Salmonella enterica derivatives harboring defined aroC and Salmonella pathogenicity island 2 type III secretion system (ssaV) mutations by immunization of healthy volunteers. Infect Immun70:3457–3467 [CrossRef][PubMed]
    [Google Scholar]
  62. Husseiny M. I., Wartha F., Hensel M.. ( 2007;). Recombinant vaccines based on translocated effector proteins of Salmonella pathogenicity island 2. Vaccine25:185–193 [CrossRef][PubMed]
    [Google Scholar]
  63. Jackson L. K., Nawabi P., Hentea C., Roark E. A., Haldar K.. ( 2008;). The Salmonella virulence protein SifA is a G protein antagonist. Proc Natl Acad Sci U S A105:14141–14146 [CrossRef][PubMed]
    [Google Scholar]
  64. Jiang X., Rossanese O. W., Brown N. F., Kujat-Choy S., Galán J. E., Finlay B. B., Brumell J. H.. ( 2004;). The related effector proteins SopD and SopD2 from Salmonella enterica serovar Typhimurium contribute to virulence during systemic infection of mice. Mol Microbiol54:1186–1198 [CrossRef][PubMed]
    [Google Scholar]
  65. Khan S. A., Stratford R., Wu T., Mckelvie N., Bellaby T., Hindle Z., Sinha K. A., Eltze S., Mastroeni P.. & other authors ( 2003;). Salmonella typhi and S. typhimurium derivatives harbouring deletions in aromatic biosynthesis and Salmonella pathogenicity island-2 (SPI-2) genes as vaccines and vectors. Vaccine21:538–548 [CrossRef][PubMed]
    [Google Scholar]
  66. Knodler L. A., Steele-Mortimer O.. ( 2005;). The Salmonella effector PipB2 affects late endosome/lysosome distribution to mediate Sif extension. Mol Biol Cell16:4108–4123 [CrossRef][PubMed]
    [Google Scholar]
  67. Knodler L. A., Celli J., Hardt W.-D., Vallance B. A., Yip C., Finlay B. B.. ( 2002;). Salmonella effectors within a single pathogenicity island are differentially expressed and translocated by separate type III secretion systems. Mol Microbiol43:1089–1103 [CrossRef][PubMed]
    [Google Scholar]
  68. Knodler L. A., Vallance B. A., Hensel M., Jäckel D., Finlay B. B., Steele-Mortimer O.. ( 2003;). Salmonella type III effectors PipB and PipB2 are targeted to detergent-resistant microdomains on internal host cell membranes. Mol Microbiol49:685–704 [CrossRef][PubMed]
    [Google Scholar]
  69. Kobe B., Kajava A. V.. ( 2001;). The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol11:725–732 [CrossRef][PubMed]
    [Google Scholar]
  70. Krause M., Fang F. C., Guiney D. G.. ( 1992;). Regulation of plasmid virulence gene expression in Salmonella dublin involves an unusual operon structure. J Bacteriol174:4482–4489[PubMed]
    [Google Scholar]
  71. Kuhle V., Hensel M.. ( 2002;). SseF and SseG are translocated effectors of the type III secretion system of Salmonella pathogenicity island 2 that modulate aggregation of endosomal compartments. Cell Microbiol4:813–824 [CrossRef][PubMed]
    [Google Scholar]
  72. Kuhle V., Jäckel D., Hensel M.. ( 2004;). Effector proteins encoded by Salmonella pathogenicity island 2 interfere with the microtubule cytoskeleton after translocation into host cells. Traffic5:356–370 [CrossRef][PubMed]
    [Google Scholar]
  73. Kuhle V., Abrahams G. L., Hensel M.. ( 2006;). Intracellular Salmonella enterica redirect exocytic transport processes in a Salmonella pathogenicity island 2-dependent manner. Traffic7:716–730 [CrossRef][PubMed]
    [Google Scholar]
  74. Kujat Choy S. L., Boyle E. C., Gal-Mor O., Goode D. L., Valdez Y., Vallance B. A., Finlay B. B.. ( 2004;). SseK1 and SseK2 are novel translocated proteins of Salmonella enterica serovar Typhimurium. Infect Immun72:5115–5125 [CrossRef][PubMed]
    [Google Scholar]
  75. Lapaque N., Hutchinson J. L., Jones D. C., Méresse S., Holden D. W., Trowsdale J., Kelly A. P.. ( 2009;). Salmonella regulates polyubiquitination and surface expression of MHC class II antigens. Proc Natl Acad Sci U S A106:14052–14057 [CrossRef][PubMed]
    [Google Scholar]
  76. Lawley T. D., Chan K., Thompson L. J., Kim C. C., Govoni G. R., Monack D. M.. ( 2006;). Genome-wide screen for Salmonella genes required for long-term systemic infection of the mouse. PLoS Pathog2:e11 [CrossRef][PubMed]
    [Google Scholar]
  77. Le Negrate G., Faustin B., Welsh K., Loeffler M., Krajewska M., Hasegawa P., Mukherjee S., Orth K., Krajewski S.. & other authors ( 2008;). Salmonella secreted factor L deubiquitinase of Salmonella typhimurium inhibits NF-κB, suppresses IκBα ubiquitination and modulates innate immune responses. J Immunol180:5045–5056[PubMed][CrossRef]
    [Google Scholar]
  78. Lee A. K., Detweiler C. S., Falkow S.. ( 2000a;). OmpR regulates the two-component system SsrA-SsrB in Salmonella pathogenicity island 2. J Bacteriol182:771–781 [CrossRef][PubMed]
    [Google Scholar]
  79. Lee C. A., Silva M., Siber A. M., Kelly A. J., Galyov E., McCormick B. A.. ( 2000b;). A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration. Proc Natl Acad Sci U S A97:12283–12288 [CrossRef][PubMed]
    [Google Scholar]
  80. Lee A. H., Zareei M. P., Daefler S.. ( 2002;). Identification of a NIPSNAP homologue as host cell target for Salmonella virulence protein SpiC. Cell Microbiol4:739–750 [CrossRef][PubMed]
    [Google Scholar]
  81. Lesnick M. L., Reiner N. E., Fierer J., Guiney D. G.. ( 2001;). The Salmonella spvB virulence gene encodes an enzyme that ADP-ribosylates actin and destabilizes the cytoskeleton of eukaryotic cells. Mol Microbiol39:1464–1470 [CrossRef][PubMed]
    [Google Scholar]
  82. Levin I., Eakin C., Blanc M.-P., Klevit R. E., Miller S. I., Brzovic P. S.. ( 2010;). Identification of an unconventional E3 binding surface on the UbcH5 ~ Ub conjugate recognized by a pathogenic bacterial E3 ligase. Proc Natl Acad Sci U S A107:2848–2853 [CrossRef][PubMed]
    [Google Scholar]
  83. Li H., Xu H., Zhou Y., Zhang J., Long C., Li S., Chen S., Zhou J.-M., Shao F.. ( 2007;). The phosphothreonine lyase activity of a bacterial type III effector family. Science315:1000–1003 [CrossRef][PubMed]
    [Google Scholar]
  84. Löber S., Jäckel D., Kaiser N., Hensel M.. ( 2006;). Regulation of Salmonella pathogenicity island 2 genes by independent environmental signals. Int J Med Microbiol296:435–447 [CrossRef][PubMed]
    [Google Scholar]
  85. Lossi N. S., Rolhion N., Magee A. I., Boyle C., Holden D. W.. ( 2008;). The Salmonella SPI-2 effector SseJ exhibits eukaryotic activator-dependent phospholipase A and glycerophospholipid : cholesterol acyltransferase activity. Microbiology154:2680–2688 [CrossRef][PubMed]
    [Google Scholar]
  86. Lyon C. E., Sadigh K. S., Carmolli M. P., Harro C., Sheldon E., Lindow J. C., Larsson C. J., Martinez T., Feller A.. & other authors ( 2010;). In a randomized, double-blinded, placebo-controlled trial, the single oral dose typhoid vaccine, M01ZH09, is safe and immunogenic at doses up to 1.7×1010 colony-forming units. Vaccine28:3602–3608 [CrossRef][PubMed]
    [Google Scholar]
  87. Majowicz S. E., Musto J., Scallan E., Angulo F. J., Kirk M., O’Brien S. J., Jones T. F., Fazil A., Hoekstra R. M.. International Collaboration on Enteric Disease ‘Burden of Illness’ Studies ( 2010;). The global burden of nontyphoidal Salmonella gastroenteritis. Clin Infect Dis50:882–889 [CrossRef][PubMed]
    [Google Scholar]
  88. Matsui H., Bacot C. M., Garlington W. A., Doyle T. J., Roberts S., Gulig P. A.. ( 2001;). Virulence plasmid-borne spvB and spvC genes can replace the 90-kilobase plasmid in conferring virulence to Salmonella enterica serovar Typhimurium in subcutaneously inoculated mice. J Bacteriol183:4652–4658 [CrossRef][PubMed]
    [Google Scholar]
  89. Mazurkiewicz P., Thomas J., Thompson J. A., Liu M., Arbibe L., Sansonetti P., Holden D. W.. ( 2008;). SpvC is a Salmonella effector with phosphothreonine lyase activity on host mitogen-activated protein kinases. Mol Microbiol67:1371–1383 [CrossRef][PubMed]
    [Google Scholar]
  90. McLaughlin L. M., Govoni G. R., Gerke C., Gopinath S., Peng K., Laidlaw G., Chien Y. H., Jeong H. W., Li Z.. & other authors ( 2009;). The Salmonella SPI2 effector SseI mediates long-term systemic infection by modulating host cell migration. PLoS Pathog5:e1000671 [CrossRef][PubMed]
    [Google Scholar]
  91. McMahon H. T., Gallop J. L.. ( 2005;). Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature438:590–596 [CrossRef][PubMed]
    [Google Scholar]
  92. Méresse S., Unsworth K. E., Habermann A., Griffiths G., Fang F., Martínez-Lorenzo M. J., Waterman S. R., Gorvel J.-P., Holden D. W.. ( 2001;). Remodelling of the actin cytoskeleton is essential for replication of intravacuolar Salmonella . Cell Microbiol3:567–577 [CrossRef][PubMed]
    [Google Scholar]
  93. Miao E. A., Miller S. I.. ( 2000;). A conserved amino acid sequence directing intracellular type III secretion by Salmonella typhimurium . Proc Natl Acad Sci U S A97:7539–7544 [CrossRef][PubMed]
    [Google Scholar]
  94. Miao E. A., Scherer C. A., Tsolis R. M., Kingsley R. A., Adams L. G., Bäumler A. J., Miller S. I.. ( 1999;). Salmonella typhimurium leucine-rich repeat proteins are targeted to the SPI1 and SPI2 type III secretion systems. Mol Microbiol34:850–864 [CrossRef][PubMed]
    [Google Scholar]
  95. Miao E. A., Brittnacher M., Haraga A., Jeng R. L., Welch M. D., Miller S. I.. ( 2003;). Salmonella effectors translocated across the vacuolar membrane interact with the actin cytoskeleton. Mol Microbiol48:401–415 [CrossRef][PubMed]
    [Google Scholar]
  96. Mills E., Baruch K., Charpentier X., Kobi S., Rosenshine I.. ( 2008;). Real-time analysis of effector translocation by the type III secretion system of enteropathogenic Escherichia coli . Cell Host Microbe3:104–113 [CrossRef][PubMed]
    [Google Scholar]
  97. Mota L. J., Ramsden A. E., Liu M., Castle J. D., Holden D. W.. ( 2009;). SCAMP3 is a component of the Salmonella-induced tubular network and reveals an interaction between bacterial effectors and post-Golgi trafficking. Cell Microbiol11:1236–1253 [CrossRef][PubMed]
    [Google Scholar]
  98. Mueller C. A., Broz P., Cornelis G. R.. ( 2008;). The type III secretion system tip complex and translocon. Mol Microbiol68:1085–1095 [CrossRef][PubMed]
    [Google Scholar]
  99. Nawabi P., Catron D. M., Haldar K.. ( 2008;). Esterification of cholesterol by a type III secretion effector during intracellular Salmonella infection. Mol Microbiol68:173–185 [CrossRef][PubMed]
    [Google Scholar]
  100. Newton H. J., Pearson J. S., Badea L., Kelly M., Lucas M., Holloway G., Wagstaff K. M., Dunstone M. A., Sloan J.. & other authors ( 2010;). The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-κB p65. PLoS Pathog6:e1000898 [CrossRef][PubMed]
    [Google Scholar]
  101. Niemann G. S., Brown R. N., Gustin J. K., Stufkens A., Shaikh-Kidwai A. S., Li J., McDermott J. E., Brewer H. M., Schepmoes A.. & other authors ( 2011;). Discovery of novel secreted virulence factors from Salmonella enterica serovar Typhimurium by proteomic analysis of culture supernatants. Infect Immun79:33–43 [CrossRef][PubMed]
    [Google Scholar]
  102. Ochman H., Groisman E. A.. ( 1996;). Distribution of pathogenicity islands in Salmonella spp. Infect Immun64:5410–5412[PubMed]
    [Google Scholar]
  103. Ochman H., Soncini F. C., Solomon F., Groisman E. A.. ( 1996;). Identification of a pathogenicity island required for Salmonella survival in host cells. Proc Natl Acad Sci U S A93:7800–7804 [CrossRef][PubMed]
    [Google Scholar]
  104. Ohlson M. B., Fluhr K., Birmingham C. L., Brumell J. H., Miller S. I.. ( 2005;). SseJ deacylase activity by Salmonella enterica serovar Typhimurium promotes virulence in mice. Infect Immun73:6249–6259 [CrossRef][PubMed]
    [Google Scholar]
  105. Ohlson M. B., Huang Z., Alto N. M., Blanc M.-P., Dixon J. E., Chai J., Miller S. I.. ( 2008;). Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Cell Host Microbe4:434–446 [CrossRef][PubMed]
    [Google Scholar]
  106. Panthel K., Meinel K. M., Domènech V. E. S., Retzbach H., Igwe E. I., Hardt W.-D., Rüssmann H.. ( 2005;). Salmonella pathogenicity island 2-mediated overexpression of chimeric SspH2 proteins for simultaneous induction of antigen-specific CD4 and CD8 T cells. Infect Immun73:334–341 [CrossRef][PubMed]
    [Google Scholar]
  107. Parkhill J., Dougan G., James K. D., Thomson N. R., Pickard D., Wain J., Churcher C., Mungall K. L., Bentley S. D.. & other authors ( 2001;). Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature413:848–852 [CrossRef][PubMed]
    [Google Scholar]
  108. Patel J. C., Galán J. E.. ( 2005;). Manipulation of the host actin cytoskeleton by Salmonella–all in the name of entry. Curr Opin Microbiol8:10–15 [CrossRef][PubMed]
    [Google Scholar]
  109. Petrache H. I., Harries D., Parsegian V. A.. ( 2005;). Alteration of lipid membrane rigidity by cholesterol and its metabolic precursors. Macromol Symp219:39–50 [CrossRef]
    [Google Scholar]
  110. Pickart C. M., Eddins M. J.. ( 2004;). Ubiquitin: structures, functions, mechanisms. Biochim Biophys Acta1695:55–72 [CrossRef][PubMed]
    [Google Scholar]
  111. Poh J., Odendall C., Spanos A., Boyle C., Liu M., Freemont P., Holden D. W.. ( 2008;). SteC is a Salmonella kinase required for SPI-2-dependent F-actin remodelling. Cell Microbiol10:20–30[PubMed]
    [Google Scholar]
  112. Quezada C. M., Hicks S. W., Galán J. E., Stebbins C. E.. ( 2009;). A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases. Proc Natl Acad Sci U S A106:4864–4869 [CrossRef][PubMed]
    [Google Scholar]
  113. Ramsden A. E., Holden D. W., Mota L. J.. ( 2007;). Membrane dynamics and spatial distribution of Salmonella-containing vacuoles. Trends Microbiol15:516–524 [CrossRef][PubMed]
    [Google Scholar]
  114. Rathman M., Barker L. P., Falkow S.. ( 1997;). The unique trafficking pattern of Salmonella typhimurium-containing phagosomes in murine macrophages is independent of the mechanism of bacterial entry. Infect Immun65:1475–1485[PubMed]
    [Google Scholar]
  115. Reinicke A. T., Hutchinson J. L., Magee A. I., Mastroeni P., Trowsdale J., Kelly A. P.. ( 2005;). A Salmonella typhimurium effector protein SifA is modified by host cell prenylation and S-acylation machinery. J Biol Chem280:14620–14627 [CrossRef][PubMed]
    [Google Scholar]
  116. Rhen M., Virtanen M., Mäkelä P. H.. ( 1989;). Localization by insertion mutagenesis of a virulence-associated region on the Salmonella typhimurium 96 kilobase pair plasmid. Microb Pathog6:153–158 [CrossRef][PubMed]
    [Google Scholar]
  117. Richter-Dahlfors A., Buchan A. M. J., Finlay B. B.. ( 1997;). Murine salmonellosis studied by confocal microscopy: Salmonella typhimurium resides intracellularly inside macrophages and exerts a cytotoxic effect on phagocytes in vivo . J Exp Med186:569–580 [CrossRef][PubMed]
    [Google Scholar]
  118. Rohde J. R., Breitkreutz A., Chenal A., Sansonetti P. J., Parsot C.. ( 2007;). Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe1:77–83 [CrossRef][PubMed]
    [Google Scholar]
  119. Rosa-Ferreira C., Munro S.. ( 2011;). Arl8 and SKIP act together to link lysosomes to kinesin-1. Dev Cell21:1171–1178 [CrossRef][PubMed]
    [Google Scholar]
  120. Roudier C., Fierer J., Guiney D. G.. ( 1992;). Characterization of translation termination mutations in the spv operon of the Salmonella virulence plasmid pSDL2. J Bacteriol174:6418–6423[PubMed]
    [Google Scholar]
  121. Ruiz-Albert J., Yu X. J., Beuzón C. R., Blakey A. N., Galyov E. E., Holden D. W.. ( 2002;). Complementary activities of SseJ and SifA regulate dynamics of the Salmonella typhimurium vacuolar membrane. Mol Microbiol44:645–661 [CrossRef][PubMed]
    [Google Scholar]
  122. Rytkönen A., Poh J., Garmendia J., Boyle C., Thompson A., Liu M., Freemont P., Hinton J. C., Holden D. W.. ( 2007;). SseL, a Salmonella deubiquitinase required for macrophage killing and virulence. Proc Natl Acad Sci U S A104:3502–3507 [CrossRef][PubMed]
    [Google Scholar]
  123. Salcedo S. P., Holden D. W.. ( 2003;). SseG, a virulence protein that targets Salmonella to the Golgi network. EMBO J22:5003–5014 [CrossRef][PubMed]
    [Google Scholar]
  124. Salcedo S. P., Noursadeghi M., Cohen J., Holden D. W.. ( 2001;). Intracellular replication of Salmonella typhimurium strains in specific subsets of splenic macrophages in vivo . Cell Microbiol3:587–597 [CrossRef][PubMed]
    [Google Scholar]
  125. Schroeder N., Henry T., de Chastellier C., Zhao W., Guilhon A.-A., Gorvel J.-P., Méresse S.. ( 2010;). The virulence protein SopD2 regulates membrane dynamics of Salmonella-containing vacuoles. PLoS Pathog6:e1001002 [CrossRef][PubMed]
    [Google Scholar]
  126. Sherry A. E., Inglis N. F., Stevenson A., Fraser-Pitt D., Everest P., Smith D. G. E., Roberts M.. ( 2011;). Characterisation of proteins extracted from the surface of Salmonella Typhimurium grown under SPI-2-inducing conditions by LC-ESI/MS/MS sequencing. Proteomics11:361–370 [CrossRef][PubMed]
    [Google Scholar]
  127. Shotland Y., Krämer H., Groisman E. A.. ( 2003;). The Salmonella SpiC protein targets the mammalian Hook3 protein function to alter cellular trafficking. Mol Microbiol49:1565–1576 [CrossRef][PubMed]
    [Google Scholar]
  128. Singer A. U., Rohde J. R., Lam R., Skarina T., Kagan O., Dileo R., Chirgadze N. Y., Cuff M. E., Joachimiak A.. & other authors ( 2008;). Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases. Nat Struct Mol Biol15:1293–1301 [CrossRef][PubMed]
    [Google Scholar]
  129. Sory M.-P., Cornelis G. R.. ( 1994;). Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into HeLa cells. Mol Microbiol14:583–594 [CrossRef][PubMed]
    [Google Scholar]
  130. Spanò S., Liu X., Galán J. E.. ( 2011;). Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella . Proc Natl Acad Sci U S A108:18418–18423 [CrossRef][PubMed]
    [Google Scholar]
  131. Srikanth C. V., Wall D. M., Maldonado-Contreras A., Shi H. N., Zhou D., Demma Z., Mumy K. L., McCormick B. A.. ( 2010;). Salmonella pathogenesis and processing of secreted effectors by caspase-3. Science330:390–393 [CrossRef][PubMed]
    [Google Scholar]
  132. Steele-Mortimer O.. ( 2011;). Exploitation of the ubiquitin system by invading bacteria. Traffic12:162–169 [CrossRef][PubMed]
    [Google Scholar]
  133. Steele-Mortimer O., Méresse S., Gorvel J.-P., Toh B.-H., Finlay B. B.. ( 1999;). Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway. Cell Microbiol1:33–49 [CrossRef][PubMed]
    [Google Scholar]
  134. Stein M. A., Leung K. Y., Zwick M., Garcia-del Portillo F., Finlay B. B.. ( 1996;). Identification of a Salmonella virulence gene required for formation of filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Mol Microbiol20:151–164 [CrossRef][PubMed]
    [Google Scholar]
  135. Tezcan-Merdol D., Nyman T., Lindberg U., Haag F., Koch-Nolte F., Rhen M.. ( 2001;). Actin is ADP-ribosylated by the Salmonella enterica virulence-associated protein SpvB. Mol Microbiol39:606–619 [CrossRef][PubMed]
    [Google Scholar]
  136. Tezcan-Merdol D., Engstrand L., Rhen M.. ( 2005;). Salmonella enterica SpvB-mediated ADP-ribosylation as an activator for host cell actin degradation. Int J Med Microbiol295:201–212 [CrossRef][PubMed]
    [Google Scholar]
  137. Thompson J. A., Liu M., Helaine S., Holden D. W.. ( 2011;). Contribution of the PhoP/Q regulon to survival and replication of Salmonella enterica serovar Typhimurium in macrophages. Microbiology157:2084–2093 [CrossRef][PubMed]
    [Google Scholar]
  138. Tsolis R. M., Townsend S. M., Miao E. A., Miller S. I., Ficht T. A., Adams L. G., Bäumler A. J.. ( 1999;). Identification of a putative Salmonella enterica serotype Typhimurium host range factor with homology to IpaH and YopM by signature-tagged mutagenesis. Infect Immun67:6385–6393[PubMed]
    [Google Scholar]
  139. Uchiya K.-i., Barbieri M. A., Funato K., Shah A. H., Stahl P. D., Groisman E. A.. ( 1999;). A Salmonella virulence protein that inhibits cellular trafficking. EMBO J18:3924–3933 [CrossRef][PubMed]
    [Google Scholar]
  140. van der Velden A. W. M., Lindgren S. W., Worley M. J., Heffron F.. ( 2000;). Salmonella pathogenicity island 1-independent induction of apoptosis in infected macrophages by Salmonella enterica serotype Typhimurium. Infect Immun68:5702–5709 [CrossRef][PubMed]
    [Google Scholar]
  141. Vazquez-Torres A., Xu Y., Jones-Carson J., Holden D. W., Lucia S. M., Dinauer M. C., Mastroeni P., Fang F. C.. ( 2000;). Salmonella pathogenicity island 2-dependent evasion of the phagocyte NADPH oxidase. Science287:1655–1658 [CrossRef][PubMed]
    [Google Scholar]
  142. Verhagen A. M., Kratina T. K., Hawkins C. J., Silke J., Ekert P. G., Vaux D. L.. ( 2007;). Identification of mammalian mitochondrial proteins that interact with IAPs via N-terminal IAP binding motifs. Cell Death Differ14:348–357 [CrossRef][PubMed]
    [Google Scholar]
  143. Vlisidou I., Marchés O., Dziva F., Mundy R., Frankel G., Stevens M. P.. ( 2006;). Identification and characterization of EspK, a type III secreted effector protein of enterohaemorrhagic Escherichia coli O157 : H7. FEMS Microbiol Lett263:32–40 [CrossRef][PubMed]
    [Google Scholar]
  144. Winder S. J., Ayscough K. R.. ( 2005;). Actin-binding proteins. J Cell Sci118:651–654 [CrossRef][PubMed]
    [Google Scholar]
  145. Wood M. W., Jones M. A., Watson P. R., Hedges S., Wallis T. S., Galyov E. E.. ( 1998;). Identification of a pathogenicity island required for Salmonella enteropathogenicity. Mol Microbiol29:883–891 [CrossRef][PubMed]
    [Google Scholar]
  146. Worley M. J., Ching K. H. L., Heffron F.. ( 2000;). Salmonella SsrB activates a global regulon of horizontally acquired genes. Mol Microbiol36:749–761 [CrossRef][PubMed]
    [Google Scholar]
  147. Worley M. J., Nieman G. S., Geddes K., Heffron F.. ( 2006;). Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells. Proc Natl Acad Sci U S A103:17915–17920 [CrossRef][PubMed]
    [Google Scholar]
  148. Xu L., Sowa M. E., Chen J., Li X., Gygi S. P., Harper J. W.. ( 2008;). An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex. Mol Biol Cell19:5059–5071 [CrossRef][PubMed]
    [Google Scholar]
  149. Xu X., Husseiny M. I., Goldwich A., Hensel M.. ( 2010;). Efficacy of intracellular activated promoters for generation of Salmonella-based vaccines. Infect Immun78:4828–4838 [CrossRef][PubMed]
    [Google Scholar]
  150. Yu X.-J., Ruíz-Albert J., Unsworth K. E., Garvis S., Liu M., Holden D. W.. ( 2002;). SpiC is required for secretion of Salmonella pathogenicity island 2 type III secretion system proteins. Cell Microbiol4:531–540 [CrossRef][PubMed]
    [Google Scholar]
  151. Yu X.-J., Liu M., Holden D. W.. ( 2004;). SsaM and SpiC interact and regulate secretion of Salmonella pathogenicity island 2 type III secretion system effectors and translocators. Mol Microbiol54:604–619 [CrossRef][PubMed]
    [Google Scholar]
  152. Yu X.-J., McGourty K., Liu M., Unsworth K. E., Holden D. W.. ( 2010;). pH sensing by intracellular Salmonella induces effector translocation. Science328:1040–1043 [CrossRef][PubMed]
    [Google Scholar]
  153. Zhu Y., Li H., Hu L., Wang J., Zhou Y., Pang Z., Liu L., Shao F.. ( 2008;). Structure of a Shigella effector reveals a new class of ubiquitin ligases. Nat Struct Mol Biol15:1302–1308 [CrossRef][PubMed]
    [Google Scholar]
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