Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1995 Aug;63(8):3088–3093. doi: 10.1128/iai.63.8.3088-3093.1995

Immunization of rats with synthetic peptide constructs from the glucan-binding or catalytic region of mutans streptococcal glucosyltransferase protects against dental caries.

M A Taubman 1, C J Holmberg 1, D J Smith 1
PMCID: PMC173421  PMID: 7622235

Abstract

Previously, we have described peptide constructs from two regions of glucosyltransferase (GTF) of mutans streptococci. A putative catalytic site in the amino-terminal half of the molecule and a repeated glucan-binding site in the carboxyl-terminal half of GTF were the regions upon which sequences were based. The present study explored the effects of immunization with these peptide constructs (called CAT or GLU) and with streptococcal GTFs from Streptococcus sobrinus and S. mutans on immunological, microbiological, and disease parameters. Groups of immunized Sprague-Dawley rats were infected with either 10(8) S. sobrinus 6715 or 10(8) S. mutans SJ32 organisms. Serum immunoglobulin G antibody levels, determined by enzyme-linked immunosorbent assay, to the respective peptide constructs and to the appropriate streptococcal GTF were significantly increased (after immunization) prior to infection and at the end of the experiment. Also, serum antibody from CAT-, GLU-, and S. sobrinus GTF-immunized rats inhibited S. sobrinus GTF-mediated insoluble glucan synthesis (all) and S. mutans GTF-mediated soluble glucan synthesis (all except anti-GLU) from sucrose. Immunization with the CAT or GLU peptide construct resulted in significantly reduced smooth surface and sulcal caries after infection with S. sobrinus. Sulcal dental caries after infection with S. mutans SJ32 were also significantly reduced in CAT- and GLU-immunized rats. Thus, immunization with peptides whose sequences are based on putative functional domains of mutans streptococcal GTF are protective toward a cariogenic S. sobrinus or S. mutans infection.

Full Text

The Full Text of this article is available as a PDF (316.4 KB).

Selected References

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

  1. Abo H., Matsumura T., Kodama T., Ohta H., Fukui K., Kato K., Kagawa H. Peptide sequences for sucrose splitting and glucan binding within Streptococcus sobrinus glucosyltransferase (water-insoluble glucan synthetase). J Bacteriol. 1991 Feb;173(3):989–996. doi: 10.1128/jb.173.3.989-996.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chia J. S., Lin R. H., Lin S. W., Chen J. Y., Yang C. S. Inhibition of glucosyltransferase activities of Streptococcus mutans by a monoclonal antibody to a subsequence peptide. Infect Immun. 1993 Nov;61(11):4689–4695. doi: 10.1128/iai.61.11.4689-4695.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cope P. A., Mooser G. Antibodies against active-site peptides common to glucosyltransferases of mutans streptococci. Infect Immun. 1993 Nov;61(11):4814–4817. doi: 10.1128/iai.61.11.4814-4817.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ferretti J. J., Gilpin M. L., Russell R. R. Nucleotide sequence of a glucosyltransferase gene from Streptococcus sobrinus MFe28. J Bacteriol. 1987 Sep;169(9):4271–4278. doi: 10.1128/jb.169.9.4271-4278.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Giffard P. M., Jacques N. A. Definition of a fundamental repeating unit in streptococcal glucosyltransferase glucan-binding regions and related sequences. J Dent Res. 1994 Jun;73(6):1133–1141. doi: 10.1177/00220345940730060201. [DOI] [PubMed] [Google Scholar]
  6. Hanada N., Kuramitsu H. K. Isolation and characterization of the Streptococcus mutans gtfC gene, coding for synthesis of both soluble and insoluble glucans. Infect Immun. 1988 Aug;56(8):1999–2005. doi: 10.1128/iai.56.8.1999-2005.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Honda O., Kato C., Kuramitsu H. K. Nucleotide sequence of the Streptococcus mutans gtfD gene encoding the glucosyltransferase-S enzyme. J Gen Microbiol. 1990 Oct;136(10):2099–2105. doi: 10.1099/00221287-136-10-2099. [DOI] [PubMed] [Google Scholar]
  8. Kato C., Nakano Y., Lis M., Kuramitsu H. K. Molecular genetic analysis of the catalytic site of Streptococcus mutans glucosyltransferases. Biochem Biophys Res Commun. 1992 Dec 15;189(2):1184–1188. doi: 10.1016/0006-291x(92)92329-v. [DOI] [PubMed] [Google Scholar]
  9. Loesche W. J., Eklund S., Earnest R., Burt B. Longitudinal investigation of bacteriology of human fissure decay: epidemiological studies in molars shortly after eruption. Infect Immun. 1984 Dec;46(3):765–772. doi: 10.1128/iai.46.3.765-772.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Loesche W. J. Role of Streptococcus mutans in human dental decay. Microbiol Rev. 1986 Dec;50(4):353–380. doi: 10.1128/mr.50.4.353-380.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McCabe M. M., Hamelik R. M., Smith E. E. Purification of dextran-binding protein from cariogenic Streptococcus mutans. Biochem Biophys Res Commun. 1977 Sep 9;78(1):273–278. doi: 10.1016/0006-291x(77)91250-5. [DOI] [PubMed] [Google Scholar]
  12. McCabe M. M. Purification and characterization of a primer-independent glucosyltransferase from Streptococcus mutans 6715-13 mutant 27. Infect Immun. 1985 Dec;50(3):771–777. doi: 10.1128/iai.50.3.771-777.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Michalek S. M., Shiota T., Ikeda T., Navia J. M., McGhee J. R. Virulence of Streptococcus mutans: biochemical and pathogenic characteristics of mutant isolates. Proc Soc Exp Biol Med. 1975 Nov;150(2):498–502. doi: 10.3181/00379727-150-39064. [DOI] [PubMed] [Google Scholar]
  14. Mooser G., Hefta S. A., Paxton R. J., Shively J. E., Lee T. D. Isolation and sequence of an active-site peptide containing a catalytic aspartic acid from two Streptococcus sobrinus alpha-glucosyltransferases. J Biol Chem. 1991 May 15;266(14):8916–8922. [PubMed] [Google Scholar]
  15. Mooser G., Iwaoka K. R. Sucrose 6-alpha-D-glucosyltransferase from Streptococcus sobrinus: characterization of a glucosyl-enzyme complex. Biochemistry. 1989 Jan 24;28(2):443–449. doi: 10.1021/bi00428a006. [DOI] [PubMed] [Google Scholar]
  16. Mooser G., Wong C. Isolation of a glucan-binding domain of glucosyltransferase (1,6-alpha-glucan synthase) from Streptococcus sobrinus. Infect Immun. 1988 Apr;56(4):880–884. doi: 10.1128/iai.56.4.880-884.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Russell R. R., Shiroza T., Kuramitsu H. K., Ferretti J. J. Homology of glucosyltransferase gene and protein sequences from Streptococcus sobrinus and Streptococcus mutans. J Dent Res. 1988 Mar;67(3):543–547. doi: 10.1177/00220345880670030401. [DOI] [PubMed] [Google Scholar]
  18. Smith D. J., Taubman M. A., Ebersole J. L. Local and systemic antibody response to oral administration of glucosyltransferase antigen complex. Infect Immun. 1980 May;28(2):441–450. doi: 10.1128/iai.28.2.441-450.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Smith D. J., Taubman M. A. Effect of local deposition of antigen on salivary immune responses and reaccumulation of mutans streptococci. J Clin Immunol. 1990 Sep;10(5):273–281. doi: 10.1007/BF00916703. [DOI] [PubMed] [Google Scholar]
  20. Smith D. J., Taubman M. A., Holmberg C. F., Eastcott J., King W. F., Ali-Salaam P. Antigenicity and immunogenicity of a synthetic peptide derived from a glucan-binding domain of mutans streptococcal glucosyltransferase. Infect Immun. 1993 Jul;61(7):2899–2905. doi: 10.1128/iai.61.7.2899-2905.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith D. J., Taubman M. A., King W. F., Eida S., Powell J. R., Eastcott J. Immunological characteristics of a synthetic peptide associated with a catalytic domain of mutans streptococcal glucosyltransferase. Infect Immun. 1994 Dec;62(12):5470–5476. doi: 10.1128/iai.62.12.5470-5476.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Smith D. J., Taubman M. A. Oral immunization of humans with Streptococcus sobrinus glucosyltransferase. Infect Immun. 1987 Nov;55(11):2562–2569. doi: 10.1128/iai.55.11.2562-2569.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stack W. E., Taubman M. A., Tsukuda T., Smith D. J., Ebersole J. L., Kent R. Dental caries in congenitally athymic rats. Oral Microbiol Immunol. 1990 Dec;5(6):309–314. doi: 10.1111/j.1399-302x.1990.tb00431.x. [DOI] [PubMed] [Google Scholar]
  24. Talbman M. A., Smith D. J. Effects of local immunization with Streptococcus mutans on induction of salivary immunoglobulin A antibody and experimental dental caries in rats. Infect Immun. 1974 Jun;9(6):1079–1091. doi: 10.1128/iai.9.6.1079-1091.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tam J. P., Lu Y. A. Vaccine engineering: enhancement of immunogenicity of synthetic peptide vaccines related to hepatitis in chemically defined models consisting of T- and B-cell epitopes. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9084–9088. doi: 10.1073/pnas.86.23.9084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tam J. P. Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigenic peptide system. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5409–5413. doi: 10.1073/pnas.85.15.5409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tanzer J. M., Freedman M. L. Genetic alterations of Streptococcus mutans' virulence. Adv Exp Med Biol. 1978;107:661–672. doi: 10.1007/978-1-4684-3369-2_75. [DOI] [PubMed] [Google Scholar]
  28. Taubman M. A., Smith D. J. Effects of local immunization with glucosyltransferase fractions from Streptococcus mutans on dental caries in rats and hamsters. J Immunol. 1977 Feb;118(2):710–720. [PubMed] [Google Scholar]
  29. Taubman M. A., Smith D. J., King W. F., Eastcott J. W., Bergey E. J., Levine M. J. Immune properties of glucosyltransferases from S. sobrinus. J Oral Pathol. 1988 Nov;17(9-10):466–470. doi: 10.1111/j.1600-0714.1988.tb01317.x. [DOI] [PubMed] [Google Scholar]
  30. Wong C., Hefta S. A., Paxton R. J., Shively J. E., Mooser G. Size and subdomain architecture of the glucan-binding domain of sucrose:3-alpha-D-glucosyltransferase from Streptococcus sobrinus. Infect Immun. 1990 Jul;58(7):2165–2170. doi: 10.1128/iai.58.7.2165-2170.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wren B. W. A family of clostridial and streptococcal ligand-binding proteins with conserved C-terminal repeat sequences. Mol Microbiol. 1991 Apr;5(4):797–803. doi: 10.1111/j.1365-2958.1991.tb00752.x. [DOI] [PubMed] [Google Scholar]
  32. Wren B. W., Russell R. R., Tabaqchali S. Antigenic cross-reactivity and functional inhibition by antibodies to Clostridium difficile toxin A, Streptococcus mutans glucan-binding protein, and a synthetic peptide. Infect Immun. 1991 Sep;59(9):3151–3155. doi: 10.1128/iai.59.9.3151-3155.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yamashita Y., Bowen W. H., Burne R. A., Kuramitsu H. K. Role of the Streptococcus mutans gtf genes in caries induction in the specific-pathogen-free rat model. Infect Immun. 1993 Sep;61(9):3811–3817. doi: 10.1128/iai.61.9.3811-3817.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. de Stoppelaar J. D., König K. G., Plasschaert A. J., van der Hoeven J. S. Decreased cariogenicity of a mutant of Streptococcus mutans. Arch Oral Biol. 1971 Aug;16(8):971–975. doi: 10.1016/0003-9969(71)90186-5. [DOI] [PubMed] [Google Scholar]
  35. von Eichel-Streiber C., Sauerborn M., Kuramitsu H. K. Evidence for a modular structure of the homologous repetitive C-terminal carbohydrate-binding sites of Clostridium difficile toxins and Streptococcus mutans glucosyltransferases. J Bacteriol. 1992 Oct;174(20):6707–6710. doi: 10.1128/jb.174.20.6707-6710.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES