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
2024-04-18
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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., Gicquel B., Guilhot C., Jacobs W. R. Jr 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;
    [Google Scholar]
  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., Fuerst T. R., Burlein J. E., Benson L. A., Bennett L. T., Bansal G. P., Young J. F., Lee M. H. other authors de la Cruz V. F. 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
    [Google Scholar]
  49. Xu S., Cooper A., Sturgill-Koszycki S., Chatterjee D., Orme I., Allen P., Russell D. G., van Heyningen T. 1994; Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium -infected macrophages. J Immunol 153:2568–2578
    [Google Scholar]
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