1887

Abstract

For successful infection, secretes and injects effector proteins into host cells by two distinct type three secretion systems (T3SSs) located on pathogenicity islands (SPIs)-1 and -2. The SPI-2 T3SS is involved in intracellular survival of serovar Typhimurium and systemic disease. As little is known regarding the function of the SPI-2 T3SS from serovar Typhi, the aetiological agent of typhoid fever, we investigated its role for survival in human macrophages. Mutations in the translocon (), basal secretion apparatus () and regulator () did not result in any reduction in survival under many of the conditions tested. Similar results were obtained with another Typhi strain or by using human primary cells. Results were corroborated based on complete deletion of the SPI-2 T3SS. Surprisingly, the data suggest that the SPI-2 T3SS of Typhi is not required for survival in human macrophages.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.041624-0
2010-12-01
2019-12-11
Loading full text...

Full text loading...

/deliver/fulltext/micro/156/12/3689.html?itemId=/content/journal/micro/10.1099/mic.0.041624-0&mimeType=html&fmt=ahah

References

  1. Alpuche-Aranda, C. M., Racoosin, E., Swanson, J. & Miller, S. ( 1994; ). Salmonella stimulate macrophage macropinocytosis and persist within spacious phagosomes. J Exp Med 179, 601–608.[CrossRef]
    [Google Scholar]
  2. Baron-Bodo, V., Doceur, P., Lefebvre, M., Labroquère, K., Defaye, C., Cambouris, C., Prigent, D., Salcedo, M., Boyer, A. & Nardin, A. ( 2005; ). Anti-tumor properties of human-activated macrophages produced in large scale for clinical application. Immunobiology 210, 267–277.[CrossRef]
    [Google Scholar]
  3. Basso, H., Rharbaoui, F., Staendner, L. H., Medina, E., Garcia-Del Portillo, F. & Guzman, C. A. ( 2002; ). Characterization of a novel intracellularly activated gene from Salmonella enterica serovar Typhi. Infect Immun 70, 5404–5411.[CrossRef]
    [Google Scholar]
  4. Beuzón, C. R., Salcedo, S. & Holden, D. ( 2002; ). Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines. Microbiology 148, 2705–2715.
    [Google Scholar]
  5. Brumell, J. H., Rosenberger, C., Gotto, G., Marcus, S. & Finlay, B. ( 2001; ). SifA permits survival and replication of Salmonella typhimurium in murine macrophages. Cell Microbiol 3, 75–84.[CrossRef]
    [Google Scholar]
  6. Chakravortty, D., Rohde, M., Jäger, L., Deiwick, J. & Hensel, M. ( 2005; ). Formation of a novel surface structure encoded by Salmonella Pathogenicity Island 2. EMBO J 24, 2043–2052.[CrossRef]
    [Google Scholar]
  7. Chan, K., Kim, C. C. & Falkow, S. ( 2005; ). Microarray-based detection of Salmonella enterica serovar Typhimurium transposon mutants that cannot survive in macrophages and mice. Infect Immun 73, 5438–5449.[CrossRef]
    [Google Scholar]
  8. Cheminay, C., Möhlenbrink, A. & Hensel, M. ( 2005; ). Intracellular Salmonella inhibit antigen presentation by dendritic cells. J Immunol 174, 2892–2899.[CrossRef]
    [Google Scholar]
  9. 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 Microbiol 30, 175–188.[CrossRef]
    [Google Scholar]
  10. Coombes, B. K., Brown, N., Valdez, Y., Brumell, J. & Finlay, B. ( 2004; ). Expression and secretion of Salmonella pathogenicity island-2 virulence genes in response to acidification exhibit differential requirements of a functional type III secretion apparatus and SsaL. J Biol Chem 279, 49804–49815.[CrossRef]
    [Google Scholar]
  11. Coombes, B. K., Lowden, M., Bishop, J., Wickham, M., Brown, N., Duong, N., Osborne, S., Gal-Mor, O. & Finlay, B. ( 2007; ). SseL is a Salmonella-specific translocated effector integrated into the SsrB-controlled Salmonella pathogenicity island 2 type III secretion system. Infect Immun 75, 574–580.[CrossRef]
    [Google Scholar]
  12. Daigle, F., Graham, J. E. & Curtiss, R., III ( 2001; ). Identification of Salmonella typhi genes expressed within macrophages by selective capture of transcribed sequences (SCOTS). Mol Microbiol 41, 1211–1222.
    [Google Scholar]
  13. Drecktrah, D., Knodler, L. A., Ireland, R. & Steele-Mortimer, O. ( 2006; ). The mechanism of Salmonella entry determines the vacuolar environment and intracellular gene expression. Traffic 7, 39–51.[CrossRef]
    [Google Scholar]
  14. Eriksson, S., Lucchini, S., Thompson, A., Rhen, M. & Hinton, J. C. ( 2003; ). Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica. Mol Microbiol 47, 103–118.
    [Google Scholar]
  15. Eswarappa, S. M., Janice, J., Nagarajan, A. G., Balasundaram, S. V., Karnam, G., Dixit, N. M. & Chakravortty, D. ( 2008; ). Differentially evolved genes of Salmonella pathogenicity islands: insights into the mechanism of host specificity in Salmonella. PLoS ONE 3, e3829.[CrossRef]
    [Google Scholar]
  16. Faucher, S. P., Porwollik, S., Dozois, C. M., McClelland, M. & Daigle, F. ( 2006; ). Transcriptome of Salmonella enterica serovar Typhi within macrophages revealed through the selective capture of transcribed sequences. Proc Natl Acad Sci U S A 103, 1906–1911.[CrossRef]
    [Google Scholar]
  17. Faucher, S. P., Forest, C., Béland, M. & Daigle, F. ( 2009; ). A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence. Microbiology 155, 477–488.[CrossRef]
    [Google Scholar]
  18. Fields, P. I., Swanson, R., Haidaris, C. & Heffron, F. ( 1986; ). Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A 83, 5189–5193.[CrossRef]
    [Google Scholar]
  19. Galán, J. E. & Curtiss, R., III ( 1989; ). Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells. Proc Natl Acad Sci U S A 86, 6383–6387.[CrossRef]
    [Google Scholar]
  20. Garmory, H. S., Brown, K. & Titball, R. ( 2002; ). Salmonella vaccines for use in humans: present and future perspectives. FEMS Microbiol Rev 26, 339–353.
    [Google Scholar]
  21. Garvis, S. G., Beuzón, C. & Holden, D. ( 2001; ). A role for the PhoP/Q regulon in inhibition of fusion between lysosomes and Salmonella-containing vacuoles in macrophages. Cell Microbiol 3, 731–744.[CrossRef]
    [Google Scholar]
  22. Goubau, D., Romieu-Mourez, R., Solis, M., Hernandez, E., Mesplède, T., Lin, R., Leaman, D. & Hiscott, J. ( 2009; ). Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7. Eur J Immunol 39, 527–540.[CrossRef]
    [Google Scholar]
  23. Groisman, E. A., Chiao, E., Lipps, C. & Heffron, F. ( 1989; ). Salmonella typhimurium phoP virulence gene is a transcriptional regulator. Proc Natl Acad Sci U S A 86, 7077–7081.[CrossRef]
    [Google Scholar]
  24. Gulig, P. A. & Curtiss, R., III ( 1987; ). Plasmid-associated virulence of Salmonella typhimurium. Infect Immun 55, 2891–2901.
    [Google Scholar]
  25. Halici, S., Zenk, S., Jantsch, J. & Hensel, M. ( 2008; ). Functional analysis of the Salmonella pathogenicity island 2-mediated inhibition of antigen presentation in dendritic cells. Infect Immun 76, 4924–4933.[CrossRef]
    [Google Scholar]
  26. Haraga, A., Ohlson, M. & Miller, S. ( 2008; ). Salmonellae interplay with host cells. Nat Rev Microbiol 6, 53–66.[CrossRef]
    [Google Scholar]
  27. Helaine, S., Thompson, J., Watson, K., Liu, M., Boyle, C. & Holden, D. ( 2010; ). Dynamics of intracellular bacterial replication at the single cell level. Proc Natl Acad Sci U S A 107, 3746–3751.[CrossRef]
    [Google Scholar]
  28. Hensel, M., Shea, J., Bäumler, A., Gleeson, C., Blattner, F. & Holden, D. ( 1997; ). Analysis of the boundaries of Salmonella pathogenicity island 2 and the corresponding chromosomal region of Escherichia coli K-12. J Bacteriol 179, 1105–1111.
    [Google Scholar]
  29. 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 Microbiol 30, 163–174.[CrossRef]
    [Google Scholar]
  30. Hölzer, S. U. & Hensel, M. ( 2010; ). Functional dissection of translocon proteins of the Salmonella pathogenicity island 2-encoded type III secretion system. BMC Microbiol 10, 104.[CrossRef]
    [Google Scholar]
  31. Hone, D. M., Harris, A., Chatfield, S., Dougan, G. & Levine, M. ( 1991; ). Construction of genetically defined double aro mutants of Salmonella typhi. Vaccine 9, 810–816.[CrossRef]
    [Google Scholar]
  32. Ishibashi, Y. & Arai, T. ( 1995; ). Salmonella typhi does not inhibit phagosome-lysosome fusion in human monocyte-derived macrophages. FEMS Immunol Med Microbiol 12, 55–61.[CrossRef]
    [Google Scholar]
  33. Kaniga, K., Compton, M. S., Curtiss, R., III & Sundaram, P. ( 1998; ). Molecular and functional characterization of Salmonella enterica serovar Typhimurium poxA gene: effect on attenuation of virulence and protection. Infect Immun 66, 5599–5606.
    [Google Scholar]
  34. 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 Microbiol 4, 813–824.[CrossRef]
    [Google Scholar]
  35. Kuhle, V. & Hensel, M. ( 2004; ). Cellular microbiology of intracellular Salmonella enterica: functions of the type III secretion system encoded by Salmonella pathogenicity island 2. Cell Mol Life Sci 61, 2812–2826.[CrossRef]
    [Google Scholar]
  36. 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 Pathog 2, e11.[CrossRef]
    [Google Scholar]
  37. Lee, C. A., Jones, B. D. & Falkow, S. ( 1992; ). Identification of a Salmonella typhimurium invasion locus by selection for hyperinvasive mutants. Proc Natl Acad Sci U S A 89, 1847–1851.[CrossRef]
    [Google Scholar]
  38. Leung, K. Y. & Finlay, B. ( 1991; ). Intracellular replication is essential for the virulence of Salmonella typhimurium. Proc Natl Acad Sci U S A 88, 11470–11474.[CrossRef]
    [Google Scholar]
  39. Lundberg, U., Vinatzer, U., Berdnik, D., von Gabain, A. & Baccarini, M. ( 1999; ). Growth phase-regulated induction of Salmonella-induced macrophage apoptosis correlates with transient expression of SPI-1 genes. J Bacteriol 181, 3433–3437.
    [Google Scholar]
  40. McClelland, M., Sanderson, K. E., Spieth, J., Clifton, S. W., Latreille, P., Courtney, L., Porwollik, S., Ali, J., Dante, M. & other authors ( 2001; ). Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413, 852–856.[CrossRef]
    [Google Scholar]
  41. McLaughlin, L. M., Govoni, G., 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 Pathog 5, e1000671.[CrossRef]
    [Google Scholar]
  42. Miller, S. I., Kukral, A. & Mekalanos, J. ( 1989; ). A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci U S A 86, 5054–5058.[CrossRef]
    [Google Scholar]
  43. Monack, D. M., Detweiler, C. & Falkow, S. ( 2001; ). Salmonella pathogenicity island 2-dependent macrophage death is mediated in part by the host cysteine protease caspase-1. Cell Microbiol 3, 825–837.[CrossRef]
    [Google Scholar]
  44. Muotiala, A. & Mäkelä, P. ( 1993; ). Role of gamma interferon in late stages of murine salmonellosis. Infect Immun 61, 4248–4253.
    [Google Scholar]
  45. Nikolaus, T., Deiwick, J., Rappl, C., Freeman, J., Schröder, W., Miller, S. & Hensel, M. ( 2001; ). SseBCD proteins are secreted by the type III secretion system of Salmonella pathogenicity island 2 and function as a translocon. J Bacteriol 183, 6036–6045.[CrossRef]
    [Google Scholar]
  46. Ochman, H., Soncini, F., Solomon, F. & Groisman, E. ( 1996; ). Identification of a pathogenicity island required for Salmonella survival in host cells. Proc Natl Acad Sci U S A 93, 7800–7804.[CrossRef]
    [Google Scholar]
  47. Paesold, G., Guiney, D., Eckmann, L. & Kagnoff, M. ( 2002; ). Genes in the Salmonella pathogenicity island 2 and the Salmonella virulence plasmid are essential for Salmonella-induced apoptosis in intestinal epithelial cells. Cell Microbiol 4, 771–781.[CrossRef]
    [Google Scholar]
  48. Parkhill, J., Dougan, G., James, K., 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. Nature 413, 848–852.[CrossRef]
    [Google Scholar]
  49. Pfeifer, C. G., Marcus, S., Steele-Mortimer, O., Knodler, L. & Finlay, B. ( 1999; ). Salmonella typhimurium virulence genes are induced upon bacterial invasion into phagocytic and nonphagocytic cells. Infect Immun 67, 5690–5698.
    [Google Scholar]
  50. Romieu-Mourez, R., Solis, M., Nardin, A., Goubau, D., Baron-Bodo, V., Lin, R., Massie, B., Salcedo, M. & Hiscott, J. ( 2006; ). Distinct roles for IFN regulatory factor (IRF)-3 and IRF-7 in the activation of antitumor properties of human macrophages. Cancer Res 66, 10576–10585.[CrossRef]
    [Google Scholar]
  51. Rosenberg, S. A., Spiess, P. & Kleiner, D. ( 2002; ). Antitumor effects in mice of the intravenous injection of attenuated Salmonella typhimurium. J Immunother 25, 218–225.[CrossRef]
    [Google Scholar]
  52. Ruiz-Albert, J., Yu, X., Beuzón, C., Blakey, A., Galyov, E. & Holden, D. ( 2002; ). Complementary activities of SseJ and SifA regulate dynamics of the Salmonella typhimurium vacuolar membrane. Mol Microbiol 44, 645–661.[CrossRef]
    [Google Scholar]
  53. Sabbagh, S. C., Forest, C. G., Lepage, C., Leclerc, J. M. & Daigle, F. ( 2010; ). So similar, yet so different: uncovering distinctive features in the genomes of Salmonella enterica serovars Typhimurium and Typhi. FEMS Microbiol Lett 305, 1–13.[CrossRef]
    [Google Scholar]
  54. Santiviago, C. A., Reynolds, M., Porwollik, S., Choi, S., Long, F., Andrews-Polymenis, H. & McClelland, M. ( 2009; ). Analysis of pools of targeted Salmonella deletion mutants identifies novel genes affecting fitness during competitive infection in mice. PLoS Pathog 5, e1000477.[CrossRef]
    [Google Scholar]
  55. Schwan, W. R., Huang, X. Z., Hu, L. & Kopecko, D. J. ( 2000; ). Differential bacterial survival, replication, and apoptosis-inducing ability of Salmonella serovars within human and murine macrophages. Infect Immun 68, 1005–1013.[CrossRef]
    [Google Scholar]
  56. Segura, I., Casadesús, J. & Ramos-Morales, F. ( 2004; ). Use of mixed infections to study cell invasion and intracellular proliferation of Salmonella enterica in eukaryotic cell cultures. J Microbiol Methods 56, 83–91.[CrossRef]
    [Google Scholar]
  57. Shea, J. E., Hensel, M., Gleeson, C. & Holden, D. W. ( 1996; ). Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. Proc Natl Acad Sci U S A 93, 2593–2597.[CrossRef]
    [Google Scholar]
  58. Shea, J. E., Beuzon, C., Gleeson, C., Mundy, R. & Holden, D. ( 1999; ). Influence of the Salmonella typhimurium pathogenicity island 2 type III secretion system on bacterial growth in the mouse. Infect Immun 67, 213–219.
    [Google Scholar]
  59. Srinivasan, J., Tinge, S., Wright, R., Herr, J. & Curtiss, R., III ( 1995; ). Oral immunization with attenuated Salmonella expressing human sperm antigen induces antibodies in serum and the reproductive tract. Biol Reprod 53, 462–471.[CrossRef]
    [Google Scholar]
  60. Tobar, J. A., Carreño, L., Bueno, S., González, P., Mora, J., Quezada, S. & Kalergis, A. ( 2006; ). Virulent Salmonella enterica serovar Typhimurium evades adaptive immunity by preventing dendritic cells from activating T cells. Infect Immun 74, 6438–6448.[CrossRef]
    [Google Scholar]
  61. Uchiya, K., Groisman, E. & Nikai, T. ( 2004; ). Involvement of Salmonella pathogenicity island 2 in the up-regulation of interleukin-10 expression in macrophages: role of protein kinase A signal pathway. Infect Immun 72, 1964–1973.[CrossRef]
    [Google Scholar]
  62. Valdivia, R. H. & Falkow, S. ( 1997; ). Fluorescence-based isolation of bacterial genes expressed within host cells. Science 277, 2007–2011.[CrossRef]
    [Google Scholar]
  63. Waterman, S. R. & Holden, D. ( 2003; ). Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system. Cell Microbiol 5, 501–511.[CrossRef]
    [Google Scholar]
  64. Xu, T., Maloy, S. & McGuire, K. ( 2009; ). Macrophages influence Salmonella host-specificity in vivo. Microb Pathog 47, 212–222.[CrossRef]
    [Google Scholar]
  65. Yu, X. J., Liu, M. & Holden, D. ( 2004; ). SsaM and SpiC interact and regulate secretion of Salmonella pathogenicity island 2 type III secretion system effectors and translocators. Mol Microbiol 54, 604–619.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.041624-0
Loading
/content/journal/micro/10.1099/mic.0.041624-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error