Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1997 Sep;65(9):3680–3685. doi: 10.1128/iai.65.9.3680-3685.1997

Analysis of the genes encoding the antigen 85 complex and MPT51 from Mycobacterium avium.

N Ohara 1, N Ohara-Wada 1, H Kitaura 1, T Nishiyama 1, S Matsumoto 1, T Yamada 1
PMCID: PMC175524  PMID: 9284137

Abstract

The components of the fibronectin-binding antigen 85 complex (85A, 85B, and 85C) and the related protein MPB/MPT51 are major secreted proteins in Mycobacterium tuberculosis and Mycobacterium bovis BCG. The fbpA, fbpC, and mpt51 genes encoding 85A, 85C, and MPT51, respectively, were isolated from Mycobacterium avium and sequenced in this study. The structures of these genes, and that of the fbpB gene encoding the 85B protein, were conserved in these three species. The secreted amounts of 85A, 85B, 85C, and MPB/MPT51 were compared for M. tuberculosis, BCG, and M. avium. These four proteins were found in large amounts in the culture filtrates from M. tuberculosis and BCG. In contrast, in the culture filtrate from M. avium, 85B and MPT51 were abundant whereas 85A and 85C were hardly found, in spite of the presence of the encoding genes. The difference in the secretion amounts might be regulated at the transcription level. These facts might reflect host immunopathogenesis, the protective immunities against infections, and the drug susceptibilities of these organisms.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abou-Zeid C., Ratliff T. L., Wiker H. G., Harboe M., Bennedsen J., Rook G. A. Characterization of fibronectin-binding antigens released by Mycobacterium tuberculosis and Mycobacterium bovis BCG. Infect Immun. 1988 Dec;56(12):3046–3051. doi: 10.1128/iai.56.12.3046-3051.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersen P., Askgaard D., Ljungqvist L., Bennedsen J., Heron I. Proteins released from Mycobacterium tuberculosis during growth. Infect Immun. 1991 Jun;59(6):1905–1910. doi: 10.1128/iai.59.6.1905-1910.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Appelberg R., Castro A. G., Pedrosa J., Silva R. A., Orme I. M., Minóprio P. Role of gamma interferon and tumor necrosis factor alpha during T-cell-independent and -dependent phases of Mycobacterium avium infection. Infect Immun. 1994 Sep;62(9):3962–3971. doi: 10.1128/iai.62.9.3962-3971.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Belisle J. T., Vissa V. D., Sievert T., Takayama K., Brennan P. J., Besra G. S. Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science. 1997 May 30;276(5317):1420–1422. doi: 10.1126/science.276.5317.1420. [DOI] [PubMed] [Google Scholar]
  5. Borremans M., de Wit L., Volckaert G., Ooms J., de Bruyn J., Huygen K., van Vooren J. P., Stelandre M., Verhofstadt R., Content J. Cloning, sequence determination, and expression of a 32-kilodalton-protein gene of Mycobacterium tuberculosis. Infect Immun. 1989 Oct;57(10):3123–3130. doi: 10.1128/iai.57.10.3123-3130.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chaisson R. E., Hopewell P. C. Mycobacteria and AIDS mortality. Am Rev Respir Dis. 1989 Jan;139(1):1–3. doi: 10.1164/ajrccm/139.1.1. [DOI] [PubMed] [Google Scholar]
  7. Collins F. M. Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome. Clin Microbiol Rev. 1989 Oct;2(4):360–377. doi: 10.1128/cmr.2.4.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Content J., de la Cuvellerie A., De Wit L., Vincent-Levy-Frébault V., Ooms J., De Bruyn J. The genes coding for the antigen 85 complexes of Mycobacterium tuberculosis and Mycobacterium bovis BCG are members of a gene family: cloning, sequence determination, and genomic organization of the gene coding for antigen 85-C of M. tuberculosis. Infect Immun. 1991 Sep;59(9):3205–3212. doi: 10.1128/iai.59.9.3205-3212.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cooper A. M., Dalton D. K., Stewart T. A., Griffin J. P., Russell D. G., Orme I. M. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med. 1993 Dec 1;178(6):2243–2247. doi: 10.1084/jem.178.6.2243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. De Bruyn J., Huygen K., Bosmans R., Fauville M., Lippens R., Van Vooren J. P., Falmagne P., Weckx M., Wiker H. G., Harboe M. Purification, characterization and identification of a 32 kDa protein antigen of Mycobacterium bovis BCG. Microb Pathog. 1987 May;2(5):351–366. doi: 10.1016/0882-4010(87)90077-5. [DOI] [PubMed] [Google Scholar]
  11. De Wit L., de la Cuvellerie A., Ooms J., Content J. Nucleotide sequence of the 32 kDa-protein gene (antigen 85 A) of Mycobacterium bovis BCG. Nucleic Acids Res. 1990 Jul 11;18(13):3995–3995. doi: 10.1093/nar/18.13.3995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Drowart A., De Bruyn J., Huygen K., Damiani G., Godfrey H. P., Stelandre M., Yernault J. C., Van Vooren J. P. Isoelectrophoretic characterization of protein antigens present in mycobacterial culture filtrates and recognized by monoclonal antibodies directed against the Mycobacterium bovis BCG antigen 85 complex. Scand J Immunol. 1992 Nov;36(5):697–702. doi: 10.1111/j.1365-3083.1992.tb03130.x. [DOI] [PubMed] [Google Scholar]
  13. Garbe T. R., Hibler N. S., Deretic V. Isoniazid induces expression of the antigen 85 complex in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1996 Jul;40(7):1754–1756. doi: 10.1128/aac.40.7.1754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harth G., Lee B. Y., Wang J., Clemens D. L., Horwitz M. A. Novel insights into the genetics, biochemistry, and immunocytochemistry of the 30-kilodalton major extracellular protein of Mycobacterium tuberculosis. Infect Immun. 1996 Aug;64(8):3038–3047. doi: 10.1128/iai.64.8.3038-3047.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Horwitz M. A., Lee B. W., Dillon B. J., Harth G. Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1530–1534. doi: 10.1073/pnas.92.5.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huygen K., Content J., Denis O., Montgomery D. L., Yawman A. M., Deck R. R., DeWitt C. M., Orme I. M., Baldwin S., D'Souza C. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med. 1996 Aug;2(8):893–898. doi: 10.1038/nm0896-893. [DOI] [PubMed] [Google Scholar]
  17. Huygen K., Palfliet K., Jurion F., Hilgers J., ten Berg R., Van Vooren J. P., De Bruyn J. H-2-linked control of in vitro gamma interferon production in response to a 32-kilodalton antigen (P32) of Mycobacterium bovis bacillus Calmette-Guérin. Infect Immun. 1988 Dec;56(12):3196–3200. doi: 10.1128/iai.56.12.3196-3200.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Huygen K., Van Vooren J. P., Turneer M., Bosmans R., Dierckx P., De Bruyn J. Specific lymphoproliferation, gamma interferon production, and serum immunoglobulin G directed against a purified 32 kDa mycobacterial protein antigen (P32) in patients with active tuberculosis. Scand J Immunol. 1988 Feb;27(2):187–194. doi: 10.1111/j.1365-3083.1988.tb02338.x. [DOI] [PubMed] [Google Scholar]
  19. Joliff G., Mathieu L., Hahn V., Bayan N., Duchiron F., Renaud M., Schechter E., Leblon G. Cloning and nucleotide sequence of the csp1 gene encoding PS1, one of the two major secreted proteins of Corynebacterium glutamicum: the deduced N-terminal region of PS1 is similar to the Mycobacterium antigen 85 complex. Mol Microbiol. 1992 Aug;6(16):2349–2362. doi: 10.1111/j.1365-2958.1992.tb01410.x. [DOI] [PubMed] [Google Scholar]
  20. Kamijo R., Le J., Shapiro D., Havell E. A., Huang S., Aguet M., Bosland M., Vilcek J. Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guérin and subsequent challenge with lipopolysaccharide. J Exp Med. 1993 Oct 1;178(4):1435–1440. doi: 10.1084/jem.178.4.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kitaura H., Ohara N., Matsuo T., Tasaka H., Kobayashi K., Yamada T. Cloning, sequencing and expression of the gene for alpha antigen from Mycobacterium intracellulare and use of PCR for the rapid identification of Mycobacterium intracellulare. Biochem Biophys Res Commun. 1993 Nov 15;196(3):1466–1473. doi: 10.1006/bbrc.1993.2417. [DOI] [PubMed] [Google Scholar]
  22. Lee B. Y., Horwitz M. A. Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis. J Clin Invest. 1995 Jul;96(1):245–249. doi: 10.1172/JCI118028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lima L. de M., Content J., van Heuverswyn H., Degrave W. Nucleotide sequence of the gene coding for the 85-B antigen of Mycobacterium leprae. Nucleic Acids Res. 1991 Oct 25;19(20):5789–5789. doi: 10.1093/nar/19.20.5789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Matsudaira P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem. 1987 Jul 25;262(21):10035–10038. [PubMed] [Google Scholar]
  25. Matsuo K., Yamaguchi R., Yamazaki A., Tasaka H., Terasaka K., Yamada T. Cloning and expression of the gene for the cross-reactive alpha antigen of Mycobacterium kansasii. Infect Immun. 1990 Feb;58(2):550–556. doi: 10.1128/iai.58.2.550-556.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Matsuo K., Yamaguchi R., Yamazaki A., Tasaka H., Yamada T. Cloning and expression of the Mycobacterium bovis BCG gene for extracellular alpha antigen. J Bacteriol. 1988 Sep;170(9):3847–3854. doi: 10.1128/jb.170.9.3847-3854.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Murray J. F., Mills J. Pulmonary infectious complications of human immunodeficiency virus infection. Part I. Am Rev Respir Dis. 1990 May;141(5 Pt 1):1356–1372. doi: 10.1164/ajrccm/141.5_Pt_1.1356. [DOI] [PubMed] [Google Scholar]
  28. Nagai S., Wiker H. G., Harboe M., Kinomoto M. Isolation and partial characterization of major protein antigens in the culture fluid of Mycobacterium tuberculosis. Infect Immun. 1991 Jan;59(1):372–382. doi: 10.1128/iai.59.1.372-382.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  30. Ohara N., Kitaura H., Hotokezaka H., Nishiyama T., Wada N., Matsumoto S., Matsuo T., Naito M., Yamada T. Characterization of the gene encoding the MPB51, one of the major secreted protein antigens of Mycobacterium bovis BCG, and identification of the secreted protein closely related to the fibronectin binding 85 complex. Scand J Immunol. 1995 May;41(5):433–442. doi: 10.1111/j.1365-3083.1995.tb03589.x. [DOI] [PubMed] [Google Scholar]
  31. Ohara N., Matsuo K., Yamaguchi R., Yamazaki A., Tasaka H., Yamada T. Cloning and sequencing of the gene for alpha antigen from Mycobacterium avium and mapping of B-cell epitopes. Infect Immun. 1993 Apr;61(4):1173–1179. doi: 10.1128/iai.61.4.1173-1179.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Orme I. M., Collins F. M. Immune response to atypical mycobacteria: immunocompetence of heavily infected mice measured in vivo fails to substantiate immunosuppression data obtained in vitro. Infect Immun. 1984 Jan;43(1):32–37. doi: 10.1128/iai.43.1.32-37.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Orme I. M. Induction of nonspecific acquired resistance and delayed-type hypersensitivity, but not specific acquired resistance in mice inoculated with killed mycobacterial vaccines. Infect Immun. 1988 Dec;56(12):3310–3312. doi: 10.1128/iai.56.12.3310-3312.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pal P. G., Horwitz M. A. Immunization with extracellular proteins of Mycobacterium tuberculosis induces cell-mediated immune responses and substantial protective immunity in a guinea pig model of pulmonary tuberculosis. Infect Immun. 1992 Nov;60(11):4781–4792. doi: 10.1128/iai.60.11.4781-4792.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pessolani M. C., Brennan P. J. Mycobacterium leprae produces extracellular homologs of the antigen 85 complex. Infect Immun. 1992 Nov;60(11):4452–4459. doi: 10.1128/iai.60.11.4452-4459.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rinke de Wit T. F., Bekelie S., Osland A., Wieles B., Janson A. A., Thole J. E. The Mycobacterium leprae antigen 85 complex gene family: identification of the genes for the 85A, 85C, and related MPT51 proteins. Infect Immun. 1993 Sep;61(9):3642–3647. doi: 10.1128/iai.61.9.3642-3647.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Salata R. A., Sanson A. J., Malhotra I. J., Wiker H. G., Harboe M., Phillips N. B., Daniel T. M. Purification and characterization of the 30,000 dalton native antigen of Mycobacterium tuberculosis and characterization of six monoclonal antibodies reactive with a major epitope of this antigen. J Lab Clin Med. 1991 Dec;118(6):589–598. [PubMed] [Google Scholar]
  38. Suzuki Y., Yoshinaga K., Ono Y., Nagata A., Yamada T. Organization of rRNA genes in Mycobacterium bovis BCG. J Bacteriol. 1987 Feb;169(2):839–843. doi: 10.1128/jb.169.2.839-843.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Takano M., Ohara N., Mizuno A., Yamada T. Cloning, sequencing and expression in Escherichia coli of the gene for alpha antigen from Mycobacterium scrofulaceum. Scand J Immunol. 1994 Aug;40(2):165–170. doi: 10.1111/j.1365-3083.1994.tb03446.x. [DOI] [PubMed] [Google Scholar]
  40. Thole J. E., Schöningh R., Janson A. A., Garbe T., Cornelisse Y. E., Clark-Curtiss J. E., Kolk A. H., Ottenhoff T. H., De Vries R. R., Abou-Zeid C. Molecular and immunological analysis of a fibronectin-binding protein antigen secreted by Mycobacterium leprae. Mol Microbiol. 1992 Jan;6(2):153–163. doi: 10.1111/j.1365-2958.1992.tb01996.x. [DOI] [PubMed] [Google Scholar]
  41. Wiker H. G., Harboe M., Nagai S., Bennedsen J. Quantitative and qualitative studies on the major extracellular antigen of Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG. Am Rev Respir Dis. 1990 Apr;141(4 Pt 1):830–838. doi: 10.1164/ajrccm/141.4_Pt_1.830. [DOI] [PubMed] [Google Scholar]
  42. Wiker H. G., Harboe M. The antigen 85 complex: a major secretion product of Mycobacterium tuberculosis. Microbiol Rev. 1992 Dec;56(4):648–661. doi: 10.1128/mr.56.4.648-661.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wiker H. G., Nagai S., Harboe M., Ljungqvist L. A family of cross-reacting proteins secreted by Mycobacterium tuberculosis. Scand J Immunol. 1992 Aug;36(2):307–319. doi: 10.1111/j.1365-3083.1992.tb03104.x. [DOI] [PubMed] [Google Scholar]
  44. Wolinsky E. Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis. 1979 Jan;119(1):107–159. doi: 10.1164/arrd.1979.119.1.107. [DOI] [PubMed] [Google Scholar]
  45. von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. doi: 10.1111/j.1432-1033.1983.tb07424.x. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES