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The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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Abstract

Streptococcus mutans is a major etiologic agent of human dental caries that forms biofilms on hard tissues in the human oral cavity, such as tooth and dentinal surfaces. Human β-defensin-3 (HBD3) is a 45-amino-acid natural antimicrobial peptide that has broad spectrum antimicrobial activity against bacteria and fungi. A synthetic peptide consisting of the C-terminal 15 amino acids of HBD3 (HBD3-C15) was recently shown to be sufficient for its antimicrobial activity. Thus, clinical applications of this peptide have garnered attention. In this study, we investigated whether HBD3-C15 inhibits the growth of the representative cariogenic pathogen Streptococcus mutans and its biofilm formation. HBD3-C15 inhibited bacterial growth, exhibited bactericidal activity, and attenuated bacterial biofilm formation in a dose-dependent manner. HBD3-C15 potentiated the bactericidal and anti-biofilm activity of calcium hydroxide (CH) and chlorhexidine digluconate (CHX), which are representative disinfectants used in dental clinics, against S. mutans. Moreover, HBD3-C15 showed antimicrobial activity by inhibiting biofilm formation by S. mutans and other dentinophilic bacteria such as Enterococcus faecalis and Streptococcus gordonii, which are associated with dental caries and endodontic infection, on human dentin slices. These effects were observed for HBD3-C15 alone and for HBD3-C15 in combination with CH or CHX. Therefore, we suggest that HBD3-C15 is a potential alternative or additive disinfectant that can be used for the treatment of oral infectious diseases, including dental caries and endodontic infections.

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References

  • Arabaci, T., Turkez, H., Canakci, C.F., and Ozgoz, M. 2013. Assessment of cytogenetic and cytotoxic effects of chlorhexidine digluconate on cultured human lymphocytes. Acta Odontol. Scand. 71, 1255–1260.

    Article  CAS  PubMed  Google Scholar 

  • Bagge, N., Hentzer, M., Andersen, J.B., Ciofu, O., Givskov, M., and Hoiby, N. 2004. Dynamics and spatial distribution of beta-lactamase expression in Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 48, 1168–1174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Batoni, G., Maisetta, G., Brancatisano, F.L., Esin, S., and Campa, M. 2011. Use of antimicrobial peptides against microbial biofilms: Advantages and limits. Curr. Med. Chem. 18, 256–279.

    Article  CAS  PubMed  Google Scholar 

  • Billings, N., Millan, M., Caldara, M., Rusconi, R., Tarasova, Y., Stocker, R., and Ribbeck, K. 2013. The extracellular matrix component psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. PLoS Pathog. 9, e1003526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bramante, C.M., Luna-Cruz, S.M., Sipert, C.R., Bernadineli, N., Garcia, R.B., de Moraes, I.G., and de Vasconcelos, B.C. 2008. Alveolar mucosa necrosis induced by utilisation of calcium hydroxide as root canal dressing. Int. Dent. J. 58, 81–85.

    Article  PubMed  Google Scholar 

  • Bridier, A., Briandet, R., Thomas, V., and Dubois-Brissonnet, F. 2011. Resistance of bacterial biofilms to disinfectants: A review. Biofouling 27, 1017–1032.

    Article  CAS  PubMed  Google Scholar 

  • Costerton, J.W., Stewart, P.S., and Greenberg, E.P. 1999. Bacterial biofilms: A common cause of persistent infections. Science 284, 1318–1322.

    Article  CAS  PubMed  Google Scholar 

  • Dhople, V., Krukemeyer, A., and Ramamoorthy, A. 2006. The human beta-defensin-3, an antibacterial peptide with multiple biological functions. Biochim. Biophys. Acta 1758, 1499–1512.

    Article  CAS  PubMed  Google Scholar 

  • Diamond, G., Beckloff, N., Weinberg, A., and Kisich, K.O. 2009. The roles of antimicrobial peptides in innate host defense. Curr. Pharm. Des. 15, 2377–2392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujii, G., Selsted, M.E., and Eisenberg, D. 1993. Defensins promote fusion and lysis of negatively charged membranes. Protein Sci. 2, 1301–1312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia, J.R., Jaumann, F., Schulz, S., Krause, A., Rodriguez-Jimenez, J., Forssmann, U., Adermann, K., Kluver, E., Vogelmeier, C., Becker, D., et al. 2001. Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res. 306, 257–264.

    CAS  PubMed  Google Scholar 

  • Gillis, R.J., White, K.G., Choi, K.H., Wagner, V.E., Schweizer, H.P., and Iglewski, B.H. 2005. Molecular basis of azithromycin-resistant Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 49, 3858–3867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta, K., Singh, S., and van Hoek, M.L. 2015. Short, synthetic cationic peptides have antibacterial activity against Mycobacterium smegmatis by forming pores in membrane and synergizing with antibiotics. Antibiotics 4, 358–378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamada, S. and Slade, H.D. 1980. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol. Rev. 44, 331–384.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hancock, R.E. 1997. Peptide antibiotics. Lancet 349, 418–422.

    Article  CAS  PubMed  Google Scholar 

  • Harder, J., Bartels, J., Christophers, E., and Schroder, J.M. 2001. Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J. Biol. Chem. 276, 5707–5713.

    Article  CAS  PubMed  Google Scholar 

  • Hoover, D.M., Rajashankar, K.R., Blumenthal, R., Puri, A., Oppenheim, J.J., Chertov, O., and Lubkowski, J. 2000. The structure of human beta-defensin-2 shows evidence of higher order oligomerization. J. Biol. Chem. 275, 32911–32918.

    Article  CAS  PubMed  Google Scholar 

  • Hoover, D.M., Wu, Z., Tucker, K., Lu, W., and Lubkowski, J. 2003. Antimicrobial characterization of human beta-defensin 3 derivatives. Antimicrob. Agents Chemother. 47, 2804–2809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou, S., Liu, Z., Young, A.W., Mark, S.L., Kallenbach, N.R., and Ren, D. 2010. Effects of trp-and arg-containing antimicrobial-peptide structure on inhibition of Escherichia coli planktonic growth and biofilm formation. Appl. Environ. Microbiol. 76, 1967–1974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jia, H.P., Schutte, B.C., Schudy, A., Linzmeier, R., Guthmiller, J.M., Johnson, G.K., Tack, B.F., Mitros, J.P., Rosenthal, A., Ganz, T., et al. 2001. Discovery of new human beta-defensins using a genomics-based approach. Gene 263, 211–218.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, B.T. 1995. Uses of chlorhexidine in dentistry. Gen. Dent. 43, 126–132, 134–140.

    CAS  PubMed  Google Scholar 

  • Jones, C.G. 1997. Chlorhexidine: Is it still the gold standard? Periodontol. 2000 15, 55–62.

    Article  CAS  Google Scholar 

  • Lee, J.K., Chang, S.W., Perinpanayagam, H., Lim, S.M., Park, Y.J., Han, S.H., Baek, S.H., Zhu, Q., Bae, K.S., and Kum, K.Y. 2013a. Antibacterial efficacy of a human beta-defensin-3 peptide on multispecies biofilms. J. Endod. 39, 1625–1629.

    Article  PubMed  Google Scholar 

  • Lee, J.K., Park, Y.J., Kum, K.Y., Han, S.H., Chang, S.W., Kaufman, B., Jiang, J., Zhu, Q., Safavi, K., and Spangberg, L. 2013b. Antimicrobial efficacy of a human beta-defensin-3 peptide using an Enterococcus faecalis dentine infection model. Int. Endod. J. 46, 406–412.

    Article  PubMed  Google Scholar 

  • Lim, S.M., Ahn, K.B., Kim, C., Kum, J.W., Perinpanayagam, H., Gu, Y., Yoo, Y.J., Chang, S.W., Han, S.H., Shon, W.J., et al. 2016. Antifungal effects of synthetic human beta-defensin 3-C15 peptide. Restor. Dent. Endod. 41, 91–97.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mah, T.F. and O’Toole, G.A. 2001. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 9, 34–39.

    Article  CAS  PubMed  Google Scholar 

  • Matsumura, K., Furukawa, S., Ogihara, H., and Morinaga, Y. 2011. Roles of multidrug efflux pumps on the biofilm formation of Escherichia coli K-12. Biocontrol Sci. 16, 69–72.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen, L.T., Haney, E.F., and Vogel, H.J. 2011. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol. 29, 464–472.

    Article  CAS  PubMed  Google Scholar 

  • Petrov, V., Funderburg, N., Weinberg, A., and Sieg, S. 2013. Human beta defensin-3 induces chemokines from monocytes and macrophages: Diminished activity in cells from hiv-infected persons. Immunology 140, 413–420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rafter, M. 2005. Apexification: A review. Dent. Traumatol. 21, 1–8.

    Article  PubMed  Google Scholar 

  • Sass, V., Schneider, T., Wilmes, M., Korner, C., Tossi, A., Novikova, N., Shamova, O., and Sahl, H.G. 2010. Human beta-defensin 3 inhibits cell wall biosynthesis in staphylococci. Infect. Immun. 78, 2793–2800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schibli, D.J., Hunter, H.N., Aseyev, V., Starner, T.D., Wiencek, J.M., McCray, P.B. Jr., Tack, B.F., and Vogel, H.J. 2002. The solution structures of the human beta-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus. J. Biol. Chem. 277, 8279–8289.

    Article  CAS  PubMed  Google Scholar 

  • Siqueira, J.F. Jr. and Lopes, H.P. 1999. Mechanisms of antimicrobial activity of calcium hydroxide: A critical review. Int. Endod. J. 32, 361–369.

    Article  PubMed  Google Scholar 

  • Vu, M., Rajgopal Bala, H., Cahill, J., Toholka, R., and Nixon, R. 2017. Immediate hypersensitivity to chlorhexidine. Australas. J. Dermatol. DOI: 10.1111/ajd.12674.

    Google Scholar 

  • Wimley, W.C., Selsted, M.E., and White, S.H. 1994. Interactions between human defensins and lipid bilayers: Evidence for formation of multimeric pores. Protein Sci. 3, 1362–1373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamasaki, K. and Gallo, R.L. 2008. Antimicrobial peptides in human skin disease. Eur. J. Dermatol. 18, 11–21.

    CAS  PubMed  Google Scholar 

  • Yang, D., Chertov, O., Bykovskaia, S.N., Chen, Q., Buffo, M.J., Shogan, J., Anderson, M., Schroder, J.M., Wang, J.M., Howard, O.M., et al. 1999. Beta-defensins: Linking innate and adaptive immunity through dendritic and t cell CCR6. Science 286, 525–528.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, 08826, Republic of Korea

    Ki Bum Ahn, A. Reum Kim & Seung Hyun Han

  2. Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup, 56212, Republic of Korea

    Ki Bum Ahn

  3. Department of Conservative Dentistry and DRI, School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea

    Kee-Yeon Kum

  4. Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea

    Cheol-Heui Yun

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  1. Ki Bum Ahn
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  2. A. Reum Kim
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  3. Kee-Yeon Kum
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  5. Seung Hyun Han
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Correspondence to Seung Hyun Han.

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Ahn, K.B., Kim, A.R., Kum, KY. et al. The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants. J Microbiol. 55, 830–836 (2017). https://doi.org/10.1007/s12275-017-7362-y

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  • DOI: https://doi.org/10.1007/s12275-017-7362-y

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