Skip to main content

Advertisement

SpringerLink
Log in

Investigating the candidacy of the serotype specific rhamnan polysaccharide based glycoconjugates to prevent disease caused by the dental pathogen Streptococcus mutans

  • Original Article
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Dental caries remains a major health issue and the Gram-positive bacterium Streptococcus mutans is considered as the major pathogen causing caries. More recently, S. mutans has been recognised as a cause of endocarditis, ulcerative colitis and fatty acid liver disease along with the likelihood of increased cerebral hemorrhage following a stroke if S. mutans is present systemically. We initiated this study to examine the vaccine candidacy of the serotype specific polysaccharides elaborated by S. mutans. We have confirmed the carbohydrate structures for the serotype specific rhamnan containing polysaccharides from serotypes c, f and k. We have prepared glycoconjugate vaccines using the rhamnan containing polymers from serotypes f and k and immunised mice and rabbits. We consistently obtained a robust immune response to the glycoconjugates with cross-reactivity consistent with the structural similarities of the polymers from the different serotypes. We developed an opsonophagocytic assay which illustrated the ability of the post-immune sera to facilitate opsonophagocytic killing of the homologous and heterologous serotypes at titers consistent with the structural homologies. We conclude that glycoconjugates of the rhamnan polymers of S. mutans are a potential vaccine candidate to target dental caries and other sequelae following the escape of S. mutans from the oral cavity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Taubman, M.A., Nash, D.A.: The scientific and public health imperative for a vaccine against dental caries. Nat. Rev. Immunol. 6, 555–563 (2006)

    Article  CAS  PubMed  Google Scholar 

  2. Nobbs, A.: Getting to the heart of the matter: Role of Streptococcus mutans adhesin Cnm in systemic disease. Virulence. 8, 1–4 (2017)

    Article  PubMed  Google Scholar 

  3. Nakano, K., Hokamura, K., Taniguchi, N., Wada, K., Kudo, C., Nomura, R., et al.: The collagen binding protein of Streptococcus mutans is involved in haemorrhagic stroke. Nat. Commun. 2, 485–494 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kojima, A., Nomura, R., Naka, S., Okawa, R., Ooshima, T., Nakano, K.: Aggravation of inflammatory bowel disease by oral streptococci. Oral Dis. 20, 359–366 (2014)

    Article  CAS  PubMed  Google Scholar 

  5. Naka, S., Nomura, R., Takashima, Y., Okawa, R., Ooshima, T., Nakano, K.: A specific Streptococcus mutans strain aggravates non-alcoholic fatty liver disease. Oral Dis. 20, 700–706 (2014)

    Article  CAS  PubMed  Google Scholar 

  6. Gould, F.K., Denning, D.W., Elliott, T.S., Foweraker, J., Perry, J.D., Prendergast, B.D., et al.: Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the working Party of the British Society for antimicrobial chemotherapy. J. Antimicrob. Chemother. 67, 269–289 (2012)

    Article  CAS  PubMed  Google Scholar 

  7. Elshibly, A., Coulter, W.A., Millar, B.C., Prendergast, B.D., Thornhill, M., Irwin, C., et al.: Effective oral health in infective endocarditis: efficacy of high street mouthwashes against the viridans group streptococci. Oral Microb. 5, 151–153 (2014)

    Google Scholar 

  8. Miller, J.H., Aviles-Reyes, A., Scott-Anne, K., Gregoire, S., Watson, G.E., Sampson, E., et al.: The collagen binding protein Cnm contributes to the oral colonisation and cariogenicity of Streptococcus mutans OMZ175. Infect. Immun. 83, 2001–2010 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Batista, M.T., Souza, R.D., Ferreira, E.L., Robinette, R., Crowley, P.J., Rodrigues, J.F., et al.: Immunogenicity and in vitro and in vivo protective effects of antibodies targeting a recombinant form of the Streptococcus mutans P1 surface protein. Infect. Immun. 82, 4978–4988 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhu, F., Zhang, H., Wu, H.: Glycosyltransferase-mediated sweet modification in oral streptococci. J. Dent. Res. 94, 659–665 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bowen, W.H., Koo, H.: Biology of Streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms. Caries Res. 45, 69–86 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Weintraub, J.A., Hilton, J.F., White, J.M., Hoover, C.I., Wycoff, K.L., Yu, L., et al.: Clinical trial of a plant-derived antibody on recolonization of mutans streptococci. Caries Res. 39, 241–250 (2005)

    Article  CAS  PubMed  Google Scholar 

  13. Hillman, J.D., McDonell, E., Cramm, T., Hillman, C.H., Zahradnik, R.T.: A spontaneous lactate dehydrogenase deficient mutant of Streptococcus rattus for use as a probiotic in the prevention of dental caries. J. Appl. Microbiol. 107, 1551–1558 (2009)

    Article  CAS  PubMed  Google Scholar 

  14. Luo, W., Wen, S., Yang, L., Zheng, G.: Mucosal anti-caries DNA vaccine: a new approach to induce protective immunity against Streptococcus mutans. Int. J. Clin. Exp. Pathol. 10, 853–857 (2017)

    Google Scholar 

  15. Smith, D.J., King, W.F., Rivero, J., Taubman, M.A.: Immunological and protective effects of di-epitopic sub-unit dental caries vaccines. Infect. Immun. 73, 2797–2804 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Childers, N.K., Michalek, S.M., Pritchard, D.G., McGhee, J.R.: Mucosal and systemic responses to an oral liposome-Streptococcus mutans carbohydrate vaccine in humans. Reg. Immunol. 3, 289–296 (1990–91)

  17. Challacombe, S.J., Russell, M.W., Hawkes, J.E., Bergmeier, L.A., Lehner, T.: Passage of immunoglobulins from plasma to the oral cavity in rhesus monkeys. Immunology. 35, 923–931 (1978)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Nakano, K., Ooshima, T.: Serotype classification of Streptococcus mutans and its detection outside the oral cavity. Future Microbiol. 4, 891–902 (2009)

    Article  CAS  PubMed  Google Scholar 

  19. Linzer, R., Reddy, M.S., Levine, M.J.: Immunochemical aspects of serotype carbohydrate antigens of Streptococcus mutans. In: Hamada, S.M., Michalek, H., Kiyono, L.M., McGhee, J.R. (eds.) Molecular Microbiology and Immunobiology of Streptococcus mutans, pp. 29–38. Elsevier Science Publishing Inc., Amsterdam (1986)

    Google Scholar 

  20. Pritchard, D.G., Gregory, R.L., Michalek, S.M., McGhee, J.R.: Characterization of the serotype e polysaccharide antigen of Streptococcus mutans. Mol. Immunol. 23, 141–145 (1986)

    Article  CAS  PubMed  Google Scholar 

  21. Linzer, R., Reddy, M.S., Levine, M.J.: Structural studies of the serotype f polysaccharide antigen from Streptococcus mutans OMZ175. Infect. Immun. 55, 3006–3010 (1987)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Fujiwara, T., Nakano, K., Kawaguchi, M., Ooshima, T., Sobue, S., Kawabata, S., et al.: Biochemical and genetic characterization of serologically untypable Streptococcus mutans strains isolated from patients with bacteremia. Eur. J. Oral Sci. 109, 330–334 (2001)

    Article  CAS  PubMed  Google Scholar 

  23. Hamada, S., Michalek, S.M., Torii, M., Morisaki, I., McGhee, J.R.: An enzyme-linked immunosorbent assay (ELISA) for quantification of antibodies to Streptococcus mutans surface antigens. Mol. Immunol. 20, 453–464 (1983)

    Article  CAS  PubMed  Google Scholar 

  24. Sawardeker, D.G., Sloneker, J.H., Jeanes, A.: Quantitative determination of monosaccharides as their alditol acetates by gas liquid chromatography. Anal. Chem. 37, 1602–1604 (1965)

    Article  CAS  Google Scholar 

  25. Cox, A.D., Li, J., Brisson, J.-R., Moxon, E.R., Richards, J.C.: Structural analysis of the lipopolysaccharide from Neisseria meningitidis strain BZ157 galE: localisation of two phosphoethanolamine residues in the inner core oligosaccharide. Carbohydr. Res. 337, 1435–1444 (2002)

    Article  CAS  PubMed  Google Scholar 

  26. Laemmli, U.K.: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227, 680–685 (1970)

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, 100, Sussex Drive, National Research Council, Ottawa, ON, K1A 0R6, Canada

    Frank St. Michael, Qingling Yang, Chantelle Cairns, Evgeny Vinogradov, Perry Fleming, Alexander C. Hayes, Annie Aubry & Andrew D. Cox

Authors
  1. Frank St. Michael
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qingling Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chantelle Cairns
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Evgeny Vinogradov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Perry Fleming
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexander C. Hayes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Annie Aubry
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrew D. Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew D. Cox.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. All animal care and accompanying procedures were in accordance with the guidelines and policies of the Canadian Council on Animal Care (CCAC). The study was approved by the Human Health Therapeutics’ Animal Care Committee which is certified by the CCAC.

Electronic supplementary material

Supplementary Fig. 1

a. 1H–NMR spectrum for the glucorhamnan and rhamnan repeating units from Streptococcus mutans serotype c strain 10499. b. 1H–NMR spectrum for the glucorhamnan and rhamnan repeating units from Streptococcus mutans serotype f strain OMZ175. c. 1H–NMR spectrum for the galactorhamnan and rhamnan repeating units from Streptococcus mutans serotype z strain OM42X. (PDF 61 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

St. Michael, F., Yang, Q., Cairns, C. et al. Investigating the candidacy of the serotype specific rhamnan polysaccharide based glycoconjugates to prevent disease caused by the dental pathogen Streptococcus mutans . Glycoconj J 35, 53–64 (2018). https://doi.org/10.1007/s10719-017-9798-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-017-9798-z

Keywords

Search

Navigation