1887

Abstract

The gene of has been shown to play a role in the survival of the avirulent within the macrophage. and analysis of Δ deletion mutants and complemented strains showed no effect on survival of in U-937 macrophages or in a mouse aerosol infection model, respectively. Further studies were done in an attempt to determine the role of in intracellular survival and to define a phenotypic difference between wild-type and the Δ deletion mutant. Bioinformatic analysis indicated that Eis is an acetyltransferase of the GCN5-related family of -acetyltransferases. Immunofluorescence microscopy and Western blot analysis studies demonstrated that Eis is released into the cytoplasm of -infected U-937 macrophages. Eis was also found in the extravesicular fraction and culture supernatant of -infected macrophages. The effect of Eis on human macrophage cytokine secretion was also examined. Eis modulated the secretion of IL-10 and TNF- by primary human monocytes in response both to infection with and to stimulation with recombinant Eis protein. These results suggest that Eis is a mycobacterial effector that is released into the host cell to modulate inflammatory responses, possibly via transcriptional or post-translational means.

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2007-02-01
2019-09-19
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References

  1. Abebe, F., Mustafa, T., Nerland, A. H. & Bjune, G. A. ( 2006; ). Cytokine profile during latent and slowly progressive primary tuberculosis: a possible role for interleukin-15 in mediating clinical disease. Clin Exp Immunol 143, 180–192.[CrossRef]
    [Google Scholar]
  2. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. ( 1990; ). Basic local alignment search tool. J Mol Biol 215, 403–410.[CrossRef]
    [Google Scholar]
  3. Barczak, A. K., Domenech, P., Boshoff, H. I., Reed, M. B., Manca, C., Kaplan, G. & Barry, C. E., 3rd ( 2005; ). In vivo phenotypic dominance in mouse mixed infections with Mycobacterium tuberculosis clinical isolates. J Infect Dis 192, 600–606.[CrossRef]
    [Google Scholar]
  4. Barker, L. P., Brooks, D. M. & Small, P. L. ( 1998; ). The identification of Mycobacterium marinum genes differentially expressed in macrophage phagosomes using promoter fusions to green fluorescent protein. Mol Microbiol 29, 1167–1177.[CrossRef]
    [Google Scholar]
  5. Barnes, P. F., Chatterjee, D., Abrams, J. S., Lu, S., Wang, E., Yamamura, M., Brennan, P. J. & Modlin, R. L. ( 1992; ). Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. J Immunol 149, 541–547.
    [Google Scholar]
  6. Beatty, W. L. & Russell, D. G. ( 2000; ). Identification of mycobacterial surface proteins released into subcellular compartments of infected macrophages. Infect Immun 68, 6997–7002.[CrossRef]
    [Google Scholar]
  7. Beatty, W. L., Rhoades, E. R., Ullrich, H. J., Chatterjee, D., Heuser, J. E. & Russell, D. G. ( 2000; ). Trafficking and release of mycobacterial lipids from infected macrophages. Traffic 1, 235–247.[CrossRef]
    [Google Scholar]
  8. Beatty, W. L., Ullrich, H. J. & Russell, D. G. ( 2001; ). Mycobacterial surface moieties are released from infected macrophages by a constitutive exocytic event. Eur J Cell Biol 80, 31–40.[CrossRef]
    [Google Scholar]
  9. Boshoff, H. I., Reed, M. B., Barry, C. E., 3rd & Mizrahi, V. ( 2003; ). DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. Cell 113, 183–193.[CrossRef]
    [Google Scholar]
  10. Brownell, J. E. & Allis, C. D. ( 1995; ). An activity gel assay detects a single, catalytically active histone acetyltransferase subunit in Tetrahymena macronuclei. Proc Natl Acad Sci U S A 92, 6364–6368.[CrossRef]
    [Google Scholar]
  11. Cappelli, G., Volpe, P., Sanduzzi, A., Sacchi, A., Colizzi, V. & Mariani, F. ( 2001; ). Human macrophage gamma interferon decreases gene expression but not replication of Mycobacterium tuberculosis: analysis of the host-pathogen reciprocal influence on transcription in a comparison of strains H37Rv and CMT97. Infect Immun 69, 7262–7270.[CrossRef]
    [Google Scholar]
  12. Chakraborty, P., Sturgill-Koszycki, S. & Russell, D. G. ( 1994; ). Isolation and characterization of pathogen-containing phagosomes. Methods Cell Biol 45, 261–276.
    [Google Scholar]
  13. Chan, J., Fan, X. D., Hunter, S. W., Brennan, P. J. & Bloom, B. R. ( 1991; ). Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages. Infect Immun 59, 1755–1761.
    [Google Scholar]
  14. Corbett, E. L., Watt, C. J., Walker, N., Maher, D., Williams, B. G., Raviglione, M. C. & Dye, C. ( 2003; ). The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 163, 1009–1021.[CrossRef]
    [Google Scholar]
  15. Dahl, J. L., Wei, J., Moulder, J. W., Laal, S. & Friedman, R. L. ( 2001; ). Subcellular localization of the intracellular survival-enhancing Eis protein of Mycobacterium tuberculosis. Infect Immun 69, 4295–4302.[CrossRef]
    [Google Scholar]
  16. Dahl, J. L., Kraus, C. N., Boshoff, H. I., Doan, B., Foley, K., Avarbock, D., Kaplan, G., Mizrahi, V., Rubin, H. & Barry, C. E., 3rd ( 2003; ). The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc Natl Acad Sci U S A 100, 10026–10031.[CrossRef]
    [Google Scholar]
  17. Dahl, J. L., Arora, K., Boshoff, H. I., Whiteford, D. C., Pacheco, S. A., Walsh, O. J., Lau-Bonilla, D., Davis, W. B. & Garza, A. G. ( 2005; ). The relA homolog of Mycobacterium smegmatis affects cell appearance, viability, and gene expression. J Bacteriol 187, 2439–2447.[CrossRef]
    [Google Scholar]
  18. D'Andrea, A., Aste-Amezaga, M., Valiante, N. M., Ma, X., Kubin, M. & Trinchieri, G. ( 1993; ). Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med 178, 1041–1048.[CrossRef]
    [Google Scholar]
  19. de Waal Malefyt, R., Abrams, J., Bennett, B., Figdor, C. G. & de Vries, J. E. ( 1991; ). Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174, 1209–1220.[CrossRef]
    [Google Scholar]
  20. Dubnau, E., Fontan, P., Manganelli, R., Soares-Appel, S. & Smith, I. ( 2002; ). Mycobacterium tuberculosis genes induced during infection of human macrophages. Infect Immun 70, 2787–2795.[CrossRef]
    [Google Scholar]
  21. Dyda, F., Klein, D. C. & Hickman, A. B. ( 2000; ). GCN5-related N-acetyltransferases: a structural overview. Annu Rev Biophys Biomol Struct 29, 81–103.[CrossRef]
    [Google Scholar]
  22. Flesch, I. E., Hess, J. H., Oswald, I. P. & Kaufmann, S. H. ( 1994; ). Growth inhibition of Mycobacterium bovis by IFN-gamma stimulated macrophages: regulation by endogenous tumor necrosis factor-alpha and by IL-10. Int Immunol 6, 693–700.[CrossRef]
    [Google Scholar]
  23. Flynn, J. L., Goldstein, M. M., Chan, J., Triebold, K. J., Pfeffer, K., Lowenstein, C. J., Schreiber, R., Mak, T. W. & Bloom, B. R. ( 1995; ). Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2, 561–572.[CrossRef]
    [Google Scholar]
  24. Fratti, R. A., Chua, J., Vergne, I. & Deretic, V. ( 2003; ). Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc Natl Acad Sci U S A 100, 5437–5442.[CrossRef]
    [Google Scholar]
  25. Fulton, S. A., Johnsen, J. M., Wolf, S. F., Sieburth, D. S. & Boom, W. H. ( 1996; ). Interleukin-12 production by human monocytes infected with Mycobacterium tuberculosis: role of phagocytosis. Infect Immun 64, 2523–2531.
    [Google Scholar]
  26. Gil, D. P., Leon, L. G., Correa, L. I., Maya, J. R., Paris, S. C., Garcia, L. F. & Rojas, M. ( 2004; ). Differential induction of apoptosis and necrosis in monocytes from patients with tuberculosis and healthy control subjects. J Infect Dis 189, 2120–2128.[CrossRef]
    [Google Scholar]
  27. Gong, J. H., Zhang, M., Modlin, R. L., Linsley, P. S., Iyer, D., Lin, Y. & Barnes, P. F. ( 1996; ). Interleukin-10 downregulates Mycobacterium tuberculosis-induced Th1 responses and CTLA-4 expression. Infect Immun 64, 913–918.
    [Google Scholar]
  28. Keane, J., Gershon, S., Wise, R. P., Mirabile-Levens, E., Kasznica, J., Schwieterman, W. D., Siegel, J. N. & Braun, M. M. ( 2001; ). Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345, 1098–1104.[CrossRef]
    [Google Scholar]
  29. Kelley, L. A., MacCallum, R. M. & Sternberg, M. J. ( 2000; ). Enhanced genome annotation using structural profiles in the program 3D-PSSM. J Mol Biol 299, 499–520.
    [Google Scholar]
  30. Lee, J. S., Song, C. H., Lim, J. H., Kim, H. J., Park, J. K., Paik, T. H., Kim, C. H., Kong, S. J., Shon, M. H. & other authors ( 2003a; ). The production of tumour necrosis factor-alpha is decreased in peripheral blood mononuclear cells from multidrug-resistant tuberculosis patients following stimulation with the 30-kDa antigen of Mycobacterium tuberculosis. Clin Exp Immunol 132, 443–449.[CrossRef]
    [Google Scholar]
  31. Lee, J. S., Song, C. H., Kim, C. H., Kong, S. J., Shon, M. H., Suhr, J. W., Jung, S. S., Lim, J. H., Kim, H. J. & other authors ( 2003b; ). Depressed interleukin-12 production by peripheral blood mononuclear cells after in vitro stimulation with the 30-kDa antigen in recurrent pulmonary tuberculosis patients. Med Microbiol Immunol 192, 61–69.
    [Google Scholar]
  32. Marchler-Bauer, A. & Bryant, S. H. ( 2004; ). CD-Search: protein domain annotations on the fly. Nucleic Acids Res 32, W327–W331.[CrossRef]
    [Google Scholar]
  33. Morris, R. P., Nguyen, L., Gatfield, J., Visconti, K., Nguyen, K., Schnappinger, D., Ehrt, S., Liu, Y., Heifets, L. & other authors ( 2005; ). Ancestral antibiotic resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 102, 12200–12205.[CrossRef]
    [Google Scholar]
  34. Neuwald, A. F. & Landsman, D. ( 1997; ). GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein. Trends Biochem Sci 22, 154–155.[CrossRef]
    [Google Scholar]
  35. Nilsson, K. & Sundstrom, C. ( 1974; ). Establishment and characteristics of two unique cell lines from patients with lymphosarcoma. Int J Cancer 13, 808–823.[CrossRef]
    [Google Scholar]
  36. Othieno, C., Hirsch, C. S., Hamilton, B. D., Wilkinson, K., Ellner, J. J. & Toossi, Z. ( 1999; ). Interaction of Mycobacterium tuberculosis-induced transforming growth factor beta 1 and interleukin-10. Infect Immun 67, 5730–5735.
    [Google Scholar]
  37. Pelicic, V., Jackson, M., Reyrat, J. M., Jacobs, W. R., Jr, Gicquel, B. & Guilhot, C. ( 1997; ). Efficient allelic exchange and transposon mutagenesis in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 94, 10955–10960.[CrossRef]
    [Google Scholar]
  38. Placido, R., Mancino, G., Amendola, A., Mariani, F., Vendetti, S., Piacentini, M., Sanduzzi, A., Bocchino, M. L., Zembala, M. & Colizzi, V. ( 1997; ). Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection. J Pathol 181, 31–38.[CrossRef]
    [Google Scholar]
  39. Rhoades, E., Hsu, F., Torrelles, J. B., Turk, J., Chatterjee, D. & Russell, D. G. ( 2003; ). Identification and macrophage-activating activity of glycolipids released from intracellular Mycobacterium bovis BCG. Mol Microbiol 48, 875–888.[CrossRef]
    [Google Scholar]
  40. Rivera-Marrero, C. A., Stewart, J., Shafer, W. M. & Roman, J. ( 2004; ). The down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilli. Infect Immun 72, 5712–5721.[CrossRef]
    [Google Scholar]
  41. Sambrook, J. E., Fritsch, E. F. & Maniatis, T. ( 1989; ). Molecular Cloning: a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  42. Saviola, B., Woolwine, S. C. & Bishai, W. R. ( 2003; ). Isolation of acid-inducible genes of Mycobacterium tuberculosis with the use of recombinase-based in vivo expression technology. Infect Immun 71, 1379–1388.[CrossRef]
    [Google Scholar]
  43. Song, C. H., Lee, J. S., Lee, S. H., Lim, K., Kim, H. J., Park, J. K., Paik, T. H. & Jo, E. K. ( 2003; ). Role of mitogen-activated protein kinase pathways in the production of tumor necrosis factor-alpha, interleukin-10, and monocyte chemotactic protein-1 by Mycobacterium tuberculosis H37Rv-infected human monocytes. J Clin Immunol 23, 194–201.[CrossRef]
    [Google Scholar]
  44. Sterner, D. E. & Berger, S. L. ( 2000; ). Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64, 435–459.[CrossRef]
    [Google Scholar]
  45. Stover, C. K., de la Cruz, V. F., Fuerst, T. R., Burlein, J. E., Benson, L. A., Bennett, L. T., Bansal, G. P., Young, J. F., Lee, M. H. & other authors ( 1991; ). New use of BCG for recombinant vaccines. Nature 351, 456–460.[CrossRef]
    [Google Scholar]
  46. Wallis, R. S., Amir-Tahmasseb, M. & Ellner, J. J. ( 1990; ). Induction of interleukin 1 and tumor necrosis factor by mycobacterial proteins: the monocyte western blot. Proc Natl Acad Sci U S A 87, 3348–3352.[CrossRef]
    [Google Scholar]
  47. Wei, J., Dahl, J. L., Moulder, J. W., Roberts, E. A., O'Gaora, P., Young, D. B. & Friedman, R. L. ( 2000; ). Identification of a Mycobacterium tuberculosis gene that enhances mycobacterial survival in macrophages. J Bacteriol 182, 377–384.[CrossRef]
    [Google Scholar]
  48. Wu, S., Howard, S. T., Samten, B., Rodrigue, S., Gaudreau, L. & Barnes, P. F. ( 2005; ). The principal sigma factor siga upregulates expression of the eis gene in a clinical Mycobacterium tuberculosis Beijing strain. In Abstracts of the Keystone Symposium on Tuberculosis, abstract no. 3118.
  49. Xu, S., Cooper, A., Sturgill-Koszycki, S., van Heyningen, T., Chatterjee, D., Orme, I., Allen, P. & Russell, D. G. ( 1994; ). Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages. J Immunol 153, 2568–2578.
    [Google Scholar]
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