Molecular Genetic and Immunological Aspects of a Major Surface Protein (the 75-kDa Protein) from Porphyromonas gingivalis

A major outer membrane protein (the 75-kDa protein) from Porphyromonas gingivalis 381 has recently been purified and characterized. In this study, the 75-kDa protein was further investigated from molecular genetic and immunological aspects. To clone a gene for the protein, its N-terminal amino acid...

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Published inNihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology) Vol. 36; no. 2; pp. 341 - 356
Main Author WATANABE, Kan-ichi
Format Journal Article
LanguageJapanese
Published JAPANESE SOCIETY OF PERIODONTOLOGY 1994
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ISSN0385-0110
1880-408X
1880-408X
DOI10.2329/perio.36.341

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Abstract A major outer membrane protein (the 75-kDa protein) from Porphyromonas gingivalis 381 has recently been purified and characterized. In this study, the 75-kDa protein was further investigated from molecular genetic and immunological aspects. To clone a gene for the protein, its N-terminal amino acid sequence was analyzed and DNA probes based on this sequence were synthesized. Using the probes, a recombinant plasmid clone carrying a single 4.2 kb BamH I fragment was isolated from pUC 19 libraries of P. gingivalis 381. The cloned 4.2 kb BamH I fragment was transferred to the bacteriophage T7 RNA polymerase/promoter vector system which produced a slightly larger 77 kDa protein immunoreactive to the antibody against the 75-kDa protein. Genomic Southern analysis revealed a single copy of the 75-kDa protein gene per genome among all P. gingivalis strains tested, and that no homologous genes were present in the other black-pigmented Bacteroides species. The 75-kDa protein gene, therefore, may be useful as a specific DNA probe to classify or detect this organism. The 75-kDa protein was shown to be immunologically species-specific when immunoblot analysis was done using whole cell lysates from the same strains and the antibody against the 75-kDa protein described above. None of the species, except for P. gingivalis strains, showed any immunoreactivity to the 75-kDa protein. To detect specific antibodies against the 75-kDa protein, immunoblot analysis with sera from periodontal patients and healthy subjects was done. As a result, 65.6% of adult periodontitis patients and 100% of rapidly progressive periodontitis patients were found to have specific antibodies against the 75-kDa protein, while the sera of gingivitis patients and healthy subjects did not show positive reactions to the protein. These findings suggested that the 75-kDa protein is an immunologically species-specific and immunodominant surface antigen. The etiology of periodontitis, especially rapidly progressive periodontitis, may be related to P. gingivalis.
AbstractList A major outer membrane protein (the 75-kDa protein) from Porphyromonas gingivalis 381 has recently been purified and characterized. In this study, the 75-kDa protein was further investigated from molecular genetic and immunological aspects. To clone a gene for the protein, its N-terminal amino acid sequence was analyzed and DNA probes based on this sequence were synthesized. Using the probes, a recombinant plasmid clone carrying a single 4.2 kb BamH I fragment was isolated from pUC 19 libraries of P. gingivalis 381. The cloned 4.2 kb BamH I fragment was transferred to the bacteriophage T7 RNA polymerase/promoter vector system which produced a slightly larger 77 kDa protein immunoreactive to the antibody against the 75-kDa protein. Genomic Southern analysis revealed a single copy of the 75-kDa protein gene per genome among all P. gingivalis strains tested, and that no homologous genes were present in the other black-pigmented Bacteroides species. The 75-kDa protein gene, therefore, may be useful as a specific DNA probe to classify or detect this organism. The 75-kDa protein was shown to be immunologically species-specific when immunoblot analysis was done using whole cell lysates from the same strains and the antibody against the 75-kDa protein described above. None of the species, except for P. gingivalis strains, showed any immunoreactivity to the 75-kDa protein. To detect specific antibodies against the 75-kDa protein, immunoblot analysis with sera from periodontal patients and healthy subjects was done. As a result, 65.6% of adult periodontitis patients and 100% of rapidly progressive periodontitis patients were found to have specific antibodies against the 75-kDa protein, while the sera of gingivitis patients and healthy subjects did not show positive reactions to the protein. These findings suggested that the 75-kDa protein is an immunologically species-specific and immunodominant surface antigen. The etiology of periodontitis, especially rapidly progressive periodontitis, may be related to P. gingivalis.
Author WATANABE, Kan-ichi
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References Lugtenberg, B., Meijers, J., Peters, R., van der Hoek, P. and van Alphen, L.: Electrophoretic resolution of themajor outer membrane protein' of Escherichia coli K 12 into four bands. FEBS. Lett., 58: 254-258, 1975.
Naito, Y., Okuda, K., Kato, T. and Takazoe, L: Monoclonal antibodies against surface antigens of Bacteroides gingivalis. Infect. Immun., 50 (1) : 231-235, 1985.
Zambon, J. J.: Microbiology of periodontal disease, Genco, R. J., Coldman, H. M. and Cohen, D. W., Contemporary Periodontics, Mosby, St. Louis, 1990, 147-160.
Van Winkelhoff, A. J., Steenbergen, T. J. M. and de Graaff, J.: The role of black-pigmented Bacteroides in human oral infections. J. Clin. Periodontol., 15: 145-155, 1988.
Hinode, D., Hayashi, H. and Nakamura, R.: Purification and characterization of three types of proteases from culture supernatants of Porphyromonas gingivalis. Infect. Immun., 59 (9) : 3060-3068, 1991.
Kurihara, H., Nishimura, F., Nakamura, T., Nakagawa, M., Tanimoto, I., Nomura, Y., Kokeguchi, S., Kato, K. and Murayama, Y.: Humoral immune response to an antigen from Porphyromonas gingivalis 381 in periodontal disease. Infect. Immun., 59 (8) : 2758-2762, 1991.
Watanabe, K., Takasawa, T., Yoshimura, F., Ozeki, M., Kawanami, M. and Kato, H.: Molecular cloning and expression of a major surface protein (the 75-kDa protein) of Porphyromonas Bacteroides) gingivalis in Esch (erichia coli. FEMS. Microbiol. Lett., 71 (1) : 47-55, 1992.
Ismaiel, M. O., Greenman, J. and Scully, C.: Serum - antibodies against the trypsin-like protease of Bacteroides gingivalis in periodontitis. J. Periodontal. Res., 23 (3) : 193-198, 1988.
Yoshimura, F., Nishikata, M., Suzuki, T., Hoover, C. I. and Newbrun, E.: Characterization of trypsinlike protease from the bacterium Bacteroides gingivalis isolated from human dental plaque. Arch. Oral. Biol., 29 (7) : 559-564, 1984.
Kawamoto, Y., Hayakawa, M. and Abiko, Y.: Purification and immunochemical characterization of a recombinant outer membrane protein from Bacteroides gingivalis. Int. J. Biochem., 23 (10) : 1053-1061, 1991.
Marmur, J.: A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J. Mol. Biol., 3: 208-218, 1961.
Yoshimura, F., Watanabe, K., Takasawa, T., Kawanami, M. and Kato, H.: Purification and properties of a 75-kilodalton major protein, an immunodominant surface antigen, from the oral anaerobe Bacteroides gingivalis. Infect. Immun., 57 (11) : 3646-3652, 1989.
Schenck, K.: IgG, IgA and IgM serum antibodies against lipopolysaccharide from Bacteroides gingivalis in periodontal health and disease. J. Periodont. Res., 20 (4) : 368-377, 1985.
Maniatis, T., Fritsch, E. F. and Sambrook, J.: Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, N. Y., 68-73, 86-96, 249-253, 312-328, 382-389, 461 -462, 1982.
Loesche, W. J.: Chemotherapy of dental plaque infections. Oral. Sci. Rev., 9: 65-107, 1976.
Sojar, H. T., Lee, J. Y., Bedi, G. S., Cho, M. I. and Genco, R. J.: Purification, characterization, and localization of a major membrane protein antigen from Porphyromonas (Bacteroides) gingivalis. Biochem. Int., 25 (3) : 437-446, 1991.
Tew, J. G., Marshall, D. R., Moore, W. E., Best, A. M., Palcanis, K. G. and Ranney, R. R.: Serum antibody reactive with predominant organisms in the subgingival flora of young adults with generalized severe periodontitis. Infect. Immun., 48 (2) : 303-311, 1985.
Yoshimura, F., Takahashi, K., Nodasaka, Y. and Suzuki, T.: Purification and characterization of a novel type of fimbriae from the oral anaerobe Bacteroides gingivalis. J. Bacteriol., 160 (3) : 949-957, 1984.
Page, R. C. and Schroeder, H. E.: Periodontitis in man and other animals. Karger, New York, 45-57, 222-239, 1982.
Klimpel, K. W. and Clark, V. L.: The RNA polymerases of Porphyromonas gingivalis and Fusobacterium nucleatum are unrelated to the RNA polywerase of Escherichia coli. J. Dent. Res., 69 (9) : 1567-1572, 1990.
Naito, Y., Okuda, K. and Takazoe, I. : Immunoglobulin G response to subgingival gram-negative bacteria in human subjects. Infect. Immun., 45 (1) : 47-51, 1984.
Fujimura, S. and Nakamura, T. : Isolation and characterization of protease from Bacteroides gingivalis. Infect. Immun., 55 (3) : 716-720, 1987.
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J.: Protein measurement with the folin phenol reagent. J. Biol. Chem., 193: 265-275, 1951.
Dzink, J. L., Tanner, A. C., Haffajee, A. D. and Socransky, S. S.: Gram negative species associated with active destructive periodontal lesions. J. Clin. Periodontol., 12 (8) : 648-659, 1985.
Nishikata, M. and Yoshimura, F.: Characterization of Porphyromonas (bacteroides) gingivalis hemagglutinin as a protease. Biochem. Biophys. Res. Commun., 178 (1) : 336-342, 1991.
Mayland, D. and Holt, S. C.: Biology of asaccharolytic black-pigmented Bacteroides species. Microbiol. Rev., 52: 134-152, 1988.
Chen, Z., Potempa, J., Polanowski, A., Wikstrom, M. and Travis, J.: Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis. J. Biol. Chem., 267 (26) : 18896-18901, 1992.
Slots, J., Listgarten, M. A.: Bacteroides gingivalis, Bacteroides intermedius and Actinobacillus actinomycetemcomitans in human periodontal diseases. J. Clin. Periodontol., 15 (2) : 85-93, 1988.
Ebersole, J. L., Taubman, M. A., Smith, D. J. and Frey, D. E.: Human immune responses to oral microorganisms: patterns of systemic antibody levels to Bacteroides species. Infect. Immun., 51 (2) : 507-513, 1986.
Tsutsui, H., Kinouchi, T., Wakano, Y. and Ohnishi, Y. : Purification and characterization of a protease from Bacteroides gingivalis 381. Infect. Immun., 55 (2) : 420-427, 1987.
Theilade, E.: The non-specific theory in microbial etiology of inflammatory periodontal disease. J. Clin. Periodontol., 13: 905-911, 1986.
Farida, R., Wilson, M. and Ivanyi, L.: Serum IgG antibodies to lipopolysaccharides in various forms of periodontal disease in man. Arch. Oral. Biol., 31 (11) : 711-715, 1986.
Yoshimura, F., Sugano, T., Kawanami, M., Kato, H. and Suzuki, T.: Detection of specific antibodies against fimbriae and membrane proteins from the oral anaerobe Bacteroides gingivalis in patients with periodontal diseases. Microbiol. Immunol., 31 (9) : 935-941, 1987.
Towbin, H., Staehelin, T. and Gordon, J.: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc. Natl. Acad. Sci. USA, 76: 4350-4354, 1979.
References_xml – reference: Page, R. C. and Schroeder, H. E.: Periodontitis in man and other animals. Karger, New York, 45-57, 222-239, 1982.
– reference: Marmur, J.: A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J. Mol. Biol., 3: 208-218, 1961.
– reference: Kawamoto, Y., Hayakawa, M. and Abiko, Y.: Purification and immunochemical characterization of a recombinant outer membrane protein from Bacteroides gingivalis. Int. J. Biochem., 23 (10) : 1053-1061, 1991.
– reference: Yoshimura, F., Watanabe, K., Takasawa, T., Kawanami, M. and Kato, H.: Purification and properties of a 75-kilodalton major protein, an immunodominant surface antigen, from the oral anaerobe Bacteroides gingivalis. Infect. Immun., 57 (11) : 3646-3652, 1989.
– reference: Yoshimura, F., Takahashi, K., Nodasaka, Y. and Suzuki, T.: Purification and characterization of a novel type of fimbriae from the oral anaerobe Bacteroides gingivalis. J. Bacteriol., 160 (3) : 949-957, 1984.
– reference: Towbin, H., Staehelin, T. and Gordon, J.: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc. Natl. Acad. Sci. USA, 76: 4350-4354, 1979.
– reference: Farida, R., Wilson, M. and Ivanyi, L.: Serum IgG antibodies to lipopolysaccharides in various forms of periodontal disease in man. Arch. Oral. Biol., 31 (11) : 711-715, 1986.
– reference: Maniatis, T., Fritsch, E. F. and Sambrook, J.: Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, N. Y., 68-73, 86-96, 249-253, 312-328, 382-389, 461 -462, 1982.
– reference: Schenck, K.: IgG, IgA and IgM serum antibodies against lipopolysaccharide from Bacteroides gingivalis in periodontal health and disease. J. Periodont. Res., 20 (4) : 368-377, 1985.
– reference: Yoshimura, F., Sugano, T., Kawanami, M., Kato, H. and Suzuki, T.: Detection of specific antibodies against fimbriae and membrane proteins from the oral anaerobe Bacteroides gingivalis in patients with periodontal diseases. Microbiol. Immunol., 31 (9) : 935-941, 1987.
– reference: Loesche, W. J.: Chemotherapy of dental plaque infections. Oral. Sci. Rev., 9: 65-107, 1976.
– reference: Slots, J., Listgarten, M. A.: Bacteroides gingivalis, Bacteroides intermedius and Actinobacillus actinomycetemcomitans in human periodontal diseases. J. Clin. Periodontol., 15 (2) : 85-93, 1988.
– reference: Ebersole, J. L., Taubman, M. A., Smith, D. J. and Frey, D. E.: Human immune responses to oral microorganisms: patterns of systemic antibody levels to Bacteroides species. Infect. Immun., 51 (2) : 507-513, 1986.
– reference: Fujimura, S. and Nakamura, T. : Isolation and characterization of protease from Bacteroides gingivalis. Infect. Immun., 55 (3) : 716-720, 1987.
– reference: Nishikata, M. and Yoshimura, F.: Characterization of Porphyromonas (bacteroides) gingivalis hemagglutinin as a protease. Biochem. Biophys. Res. Commun., 178 (1) : 336-342, 1991.
– reference: Naito, Y., Okuda, K., Kato, T. and Takazoe, L: Monoclonal antibodies against surface antigens of Bacteroides gingivalis. Infect. Immun., 50 (1) : 231-235, 1985.
– reference: Mayland, D. and Holt, S. C.: Biology of asaccharolytic black-pigmented Bacteroides species. Microbiol. Rev., 52: 134-152, 1988.
– reference: Naito, Y., Okuda, K. and Takazoe, I. : Immunoglobulin G response to subgingival gram-negative bacteria in human subjects. Infect. Immun., 45 (1) : 47-51, 1984.
– reference: Ismaiel, M. O., Greenman, J. and Scully, C.: Serum - antibodies against the trypsin-like protease of Bacteroides gingivalis in periodontitis. J. Periodontal. Res., 23 (3) : 193-198, 1988.
– reference: Kurihara, H., Nishimura, F., Nakamura, T., Nakagawa, M., Tanimoto, I., Nomura, Y., Kokeguchi, S., Kato, K. and Murayama, Y.: Humoral immune response to an antigen from Porphyromonas gingivalis 381 in periodontal disease. Infect. Immun., 59 (8) : 2758-2762, 1991.
– reference: Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J.: Protein measurement with the folin phenol reagent. J. Biol. Chem., 193: 265-275, 1951.
– reference: Zambon, J. J.: Microbiology of periodontal disease, Genco, R. J., Coldman, H. M. and Cohen, D. W., Contemporary Periodontics, Mosby, St. Louis, 1990, 147-160.
– reference: Sojar, H. T., Lee, J. Y., Bedi, G. S., Cho, M. I. and Genco, R. J.: Purification, characterization, and localization of a major membrane protein antigen from Porphyromonas (Bacteroides) gingivalis. Biochem. Int., 25 (3) : 437-446, 1991.
– reference: Watanabe, K., Takasawa, T., Yoshimura, F., Ozeki, M., Kawanami, M. and Kato, H.: Molecular cloning and expression of a major surface protein (the 75-kDa protein) of Porphyromonas Bacteroides) gingivalis in Esch (erichia coli. FEMS. Microbiol. Lett., 71 (1) : 47-55, 1992.
– reference: Dzink, J. L., Tanner, A. C., Haffajee, A. D. and Socransky, S. S.: Gram negative species associated with active destructive periodontal lesions. J. Clin. Periodontol., 12 (8) : 648-659, 1985.
– reference: Van Winkelhoff, A. J., Steenbergen, T. J. M. and de Graaff, J.: The role of black-pigmented Bacteroides in human oral infections. J. Clin. Periodontol., 15: 145-155, 1988.
– reference: Chen, Z., Potempa, J., Polanowski, A., Wikstrom, M. and Travis, J.: Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis. J. Biol. Chem., 267 (26) : 18896-18901, 1992.
– reference: Theilade, E.: The non-specific theory in microbial etiology of inflammatory periodontal disease. J. Clin. Periodontol., 13: 905-911, 1986.
– reference: Hinode, D., Hayashi, H. and Nakamura, R.: Purification and characterization of three types of proteases from culture supernatants of Porphyromonas gingivalis. Infect. Immun., 59 (9) : 3060-3068, 1991.
– reference: Lugtenberg, B., Meijers, J., Peters, R., van der Hoek, P. and van Alphen, L.: Electrophoretic resolution of themajor outer membrane protein' of Escherichia coli K 12 into four bands. FEBS. Lett., 58: 254-258, 1975.
– reference: Tew, J. G., Marshall, D. R., Moore, W. E., Best, A. M., Palcanis, K. G. and Ranney, R. R.: Serum antibody reactive with predominant organisms in the subgingival flora of young adults with generalized severe periodontitis. Infect. Immun., 48 (2) : 303-311, 1985.
– reference: Yoshimura, F., Nishikata, M., Suzuki, T., Hoover, C. I. and Newbrun, E.: Characterization of trypsinlike protease from the bacterium Bacteroides gingivalis isolated from human dental plaque. Arch. Oral. Biol., 29 (7) : 559-564, 1984.
– reference: Tsutsui, H., Kinouchi, T., Wakano, Y. and Ohnishi, Y. : Purification and characterization of a protease from Bacteroides gingivalis 381. Infect. Immun., 55 (2) : 420-427, 1987.
– reference: Klimpel, K. W. and Clark, V. L.: The RNA polymerases of Porphyromonas gingivalis and Fusobacterium nucleatum are unrelated to the RNA polywerase of Escherichia coli. J. Dent. Res., 69 (9) : 1567-1572, 1990.
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Snippet A major outer membrane protein (the 75-kDa protein) from Porphyromonas gingivalis 381 has recently been purified and characterized. In this study, the 75-kDa...
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SubjectTerms 75-kDa protein
Gene cloning
Porphyromonas gingivalis
Species-specific
Specific antibody
Title Molecular Genetic and Immunological Aspects of a Major Surface Protein (the 75-kDa Protein) from Porphyromonas gingivalis
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