Advertisement

A tooth-binding antimicrobial peptide to prevent the formation of dental biofilm

  • Li-yu Zhang
  • Ze-hui Fang
  • Quan-li Li
  • Chris Ying CaoEmail author
Biomaterials Synthesis and Characterization Original Research
  • 176 Downloads
Part of the following topical collections:
  1. Biomaterials Synthesis and Characterization

Abstract

Dental caries is primarily caused by pathogenic bacteria infection, and Streptococcus mutans is considered a major cariogenic pathogen. Moreover, antimicrobial peptides have been considered an alternative to traditional antibiotics in treating caries. This study aimed to design a tooth-binding antimicrobial peptide and evaluate its antimicrobial efficacy against S. mutans. An antimicrobial peptide of polyphemusin I (PI) was modified by grafting a tooth-binding domain of diphosphoserine (Ser(p)-Ser(p)-) to create the peptide of Ser(p)-Ser(p)-polyphemusin I (DPS-PI). PI and DPS-PI were synthesized by Fmoc solid-phase peptide synthesis. The minimum inhibitory concentration of PI and DPS-PI against S. mutans were tested. Scanning electron microscopy (SEM) were used to observe the growth of S. mutans on PI and DPS-PI treated enamel surfaces. The growth of S. mutans was evaluated by optical density (OD) at 590 nm. Inhibition of dental plaque biofilm development in vivo were investigated. The cytocompatibility to bone mesenchymal stem cells (BMSCs) was tested. The MIC of PI and DPS-PI were 40 and 80 μg/ml, respectively. SEM images showed that S. mutans were sparsely distributed on the DPS-PI treated enamel surface. OD findings indicated that DPS-PI maintained its inhibition effect on S. mutans growth after 24 h. The incisor surfaces of rabbits treated with DPS-PI developed significantly less dental plaque biofilm than that on PI treated surfaces. The DPS-PI had good biocompatibility with the cells. We successfully constructed a novel tooth-binding antimicrobial peptide against S. mutans in vitro and inhibited dental plaque biofilm development in vivo. DPS-PI may provide a feasible alternative to conventional antibiotics for the prevention and treatment of dental caries.

Dental caries is primarily caused by pathogenic bacteria infection, and Streptococcus mutans is considered a major cariogenic pathogen. A tooth-binding antimicrobial peptide was designed by grafted diphosphoserine (-Ser(p)-Ser(p)-) to the structure of polyphemusin I. This novel tooth-binding antimicrobial peptide can inhibit dental plaque biofilm development and thus provide a feasible alternative to conventional antibiotics for the prevention and treatment of dental caries.

Notes

Acknowledgements

This work was supported by Grants for Scientific Research of BSKY from Anhui Medical University (grant number XJ201538); Scientific Research Foundation of the Institute for Translational Medicine of Anhui Province (grant number 2017zhyx20).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Kolenbrander PE, Palmer RJ, Jr. Rickard AH, Jakubovics NS, Chalmers NI, Diaz PI. Bacterial interactions and successions during plaque development. Periodontol 2000. 2006;42:47–79.CrossRefGoogle Scholar
  2. 2.
    Selwitz RH, Ismail AI, Pitts NB. Dental caries. Lancet. 2007;369:51–9.CrossRefGoogle Scholar
  3. 3.
    Marsh PD. Controlling the oral biofilm with antimicrobials. J Dent. 2010;38:S11–5.CrossRefGoogle Scholar
  4. 4.
    Kalesinskas P, Kačergius T, Ambrozaitis A, Pečiulienė V, Ericson D. Reducing dental plaque formation and caries development. A review of current methods and implications for novel pharmaceuticals. Stomatologija. 2014;16:44–52.Google Scholar
  5. 5.
    Baehni PC, Takeuchi Y. Anti-plaque agents in the prevention of biofilm-associated oral diseases. Oral Dis. 2003;9:23–9.CrossRefGoogle Scholar
  6. 6.
    Shen Y, Zhao J, de la Fuente-Núñez C, Wang Z, Hancock RE, Roberts CR, et al. Experimental and theoretical investigation of multispecies oral biofilm resistance to chlorhexidine treatment. Sci Rep. 2016;6:27537.CrossRefGoogle Scholar
  7. 7.
    Marsh PD, Head DA, Devine DA. Ecological approaches to oral biofilms: control without killing. Caries Res. 2015;49:46–54.CrossRefGoogle Scholar
  8. 8.
    Gorr SU. Antimicrobial peptides of the oral cavity. Periodontol 2000. 2009;51:152–80.CrossRefGoogle Scholar
  9. 9.
    Hancock RE, Sahl HG. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol. 2006;24:1551–7.CrossRefGoogle Scholar
  10. 10.
    Pirtskhalava M, Gabrielian A, Cruz P, Griggs HL, Squires RB, Hurt DE, et al. DBAASP v.2: an enhanced database of structure and antimicrobial/cytotoxic activity of natural and synthetic peptides. Nucleic Acids Res. 2016;44:6503.CrossRefGoogle Scholar
  11. 11.
    Waghu FH, Barai RS, Gurung P, Idicula-Thomas S. CAMPR3: a database on sequences, structures and signatures of antimicrobial peptides. Nucleic Acids Res. 2016;44:D1094–7.CrossRefGoogle Scholar
  12. 12.
    Wang G, Li X, Wang Z. APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Res. 2016;44:D1087–93.CrossRefGoogle Scholar
  13. 13.
    Guaní-Guerra E, Santos-Mendoza T, Lugo-Reyes SO, Terán LM. Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin Immunol. 2010;135:1–11.CrossRefGoogle Scholar
  14. 14.
    Aoki W, Kuroda K, Ueda M. Next generation of antimicrobial peptides as molecular targeted medicines. J Biosci Bioeng. 2012;114:365–70.CrossRefGoogle Scholar
  15. 15.
    Pasupuleti M, Schmidtchen A, Malmsten M. Antimicrobial peptides: key components of the innate immune system. Crit Rev Biotechnol. 2012;32:143–71.CrossRefGoogle Scholar
  16. 16.
    Bechinger B, Gorr SU. Antimicrobial peptides: mechanisms of action and resistance. J Dent Res. 2017;96:254–60.CrossRefGoogle Scholar
  17. 17.
    da Silva BR, de Freitas VA, Nascimento-Neto LG, Carneiro VA, Arruda FV, de Aguiar AS, et al. Antimicrobial peptide control of pathogenic microorganisms of the oral cavity: a review of the literature. Peptides. 2012;36:315–21.CrossRefGoogle Scholar
  18. 18.
    Fjell CD, Hiss JA, Hancock RE, Schneider G. Designing antimicrobial peptides: form follows function. Nat Rev Drug Discov. 2011;11:37–51.CrossRefGoogle Scholar
  19. 19.
    Kreling PF, Aida KL, Massunari L, Caiaffa KS, Percinoto C, Bedran TB, et al. Cytotoxicity and the effect of cationic peptide fragments against cariogenic bacteria under planktonic and biofilm conditions. Biofouling. 2016;32:995–1006.CrossRefGoogle Scholar
  20. 20.
    Chen L, Jia L, Zhang Q, Zhou X, Liu Z, Li B, et al. A novel antimicrobial peptide against dental-caries-associated bacteria. Anaerobe. 2017;47:165–72.CrossRefGoogle Scholar
  21. 21.
    Sullivan R, Santarpia P, Lavender S, Gittins E, Liu Z, Anderson MH, et al. Clinical efficacy of a specifically targeted antimicrobial peptide mouth rinse: targeted elimination of Streptococcus mutans and prevention of demineralization. Caries Res. 2011;45:415–28.CrossRefGoogle Scholar
  22. 22.
    Huang ZB, Shi X, Mao J, Gong SQ. Design of a hydroxyapatite-binding antimicrobial peptide with improved retention and antibacterial efficacy for oral pathogen control. Sci Rep. 2016;6:38410.CrossRefGoogle Scholar
  23. 23.
    Powers JP, Rozek A, Hancock RE. Hancock, Structure-activity relationships for the beta-hairpin cationic antimicrobial peptide polyphemusin I. Biochim Biophys Acta. 2004;1698:239–50.CrossRefGoogle Scholar
  24. 24.
    Chen F, Jia Z, Rice KC, Reinhardt RA, Bayles KW, Wang D. The development of dentotropic micelles with biodegradable tooth-binding moieties. Pharm Res. 2013;30:2808–17.CrossRefGoogle Scholar
  25. 25.
    Hojo K, Nagaoka S, Ohshima T, Maeda N. Bacterial interactions in dental biofilm development. J Dent Res. 2009;88:982–90.CrossRefGoogle Scholar
  26. 26.
    Wang Z, Shen Y, Haapasalo M. Antibiofilm peptides against oral biofilms. J Oral Microbiol. 2017;9:1327308.CrossRefGoogle Scholar
  27. 27.
    Rapaport D, Shai Y. Interaction of fluorescently labeled pardaxin and its analogues with lipid bilayers. J Biol Chem. 1991;266:23769–75.Google Scholar
  28. 28.
    Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW. Membrane pores induced by magainin. Biochemistry. 1996;35:13723–8.CrossRefGoogle Scholar
  29. 29.
    Gazit E, Miller IR, Biggin PC, Sansom MS, Shai Y. Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes. J Mol Biol. 1996;258:860–70.CrossRefGoogle Scholar
  30. 30.
    Sang Y, Blecha F. Antimicrobial peptides and bacteriocins: alternatives to traditional antibiotics. Anim Health Res Rev. 2008;9:227–35.CrossRefGoogle Scholar
  31. 31.
    Wang Z, de la Fuente-Núñez C, Shen Y, Haapasalo M, Hancock RE. Treatment of oral multispecies biofilms by an anti-biofilm peptide. PLoS ONE. 2015;10:e0132512.CrossRefGoogle Scholar
  32. 32.
    Ding Y, Wang W, Fan M, Tong Z, Kuang R, Jiang W, et al. Antimicrobial and anti-biofilm effect of Bac8c on major bacteria associated with dental caries and Streptococcus mutans biofilms. Peptides. 2014;52:61–7.CrossRefGoogle Scholar
  33. 33.
    Ohta M, Ito H, Masuda K, Tanaka S, Arakawa Y, Wacharotayankun R, et al. Mechanisms of antibacterial action of tachyplesins and polyphemusins, a group of antimicrobial peptides isolated from horseshoe crab hemocytes. Antimicrob Agents Chemother. 1992;36:1460–5.CrossRefGoogle Scholar
  34. 34.
    Edwards IA, Elliott AG, Kavanagh AM, Zuegg J, Blaskovich MA, Cooper MA. Contribution of amphipathicity and hydrophobicity to the antimicrobial activity and cytotoxicity of beta-hairpin peptides. ACS Infect Dis. 2016;2:442–50.CrossRefGoogle Scholar
  35. 35.
    Zhang L, Rozek A, Hancock RE. Interaction of cationic antimicrobial peptides with model membranes. J Biol Chem. 2001;276:35714–22.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Li-yu Zhang
    • 1
  • Ze-hui Fang
    • 1
  • Quan-li Li
    • 1
  • Chris Ying Cao
    • 1
    Email author
  1. 1.Key Laboratory of Oral Diseases Research of Anhui Province, College and Hospital of StomatologyAnhui Medical UniversityHefeiChina

Personalised recommendations