Skip to main content

Advertisement

Log in

Antimicrobial Peptides and their Potential as Oral Therapeutic Agents

  • Special Issue: Peptides in Oral and Dental Research
  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Dental caries (tooth decay) and periodontal diseases are the most prevalent bacterial infectious diseases of mankind, together affecting almost the entire population of the world. Both diseases are caused by oral bacteria that exist as components of a polymicrobial biofilm, known as dental plaque, on the tooth surface. The control of specific types of bacteria and/or total numbers of bacteria in dental plaque could lead to prevention or resolution of disease. Antimicrobial peptides isolated from a wide range of natural sources have been known for over 30 years yet little progress had been made in the therapeutic application of these peptides. This is due in part to the characteristics, including susceptibility to proteolysis, of the cationic amphipathic antimicrobial peptides that form the majority of peptides discovered to date. Bovine milk is a readily available source of a range of bioactive peptides. We have isolated and characterized a novel anionic antimicrobial peptide, Kappacin, from bovine milk. Antibacterial activity of the peptide is increased when it is complexed with zinc ions. We have demonstrated that a Kappacin:Zn2+ preparation is able to suppress the growth of oral cariogenic bacteria in a biofilm. The Kappacin:Zn2+ antibacterial complex may have potential as an additive to oral care products and other delivery vehicles for the control of oral disease.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Addy M., Hassan H., Moran J., Wade W., Newcombe R. (1988) J. Periodontol. 59:557–564

    PubMed  CAS  Google Scholar 

  • Aguilera O., Quiros L. M., Fierro J. F. (2003) FEBS Lett. 548:5–10

    Article  PubMed  CAS  Google Scholar 

  • Andreu D., Aschauer H., Kreil G., Merrifield R. B. (1985) Eur. J. Biochem. 149:531–535

    Article  PubMed  CAS  Google Scholar 

  • Apponyi M. A., Pukala T. L., Brinkworth C. S., Maselli V. M., Bowie J. H., Tyler M. J., Booker G. W., Wallace J. C., Carver J. A., Separovic F., Doyle J., Llewellyn L. E. (2004) Peptides 25:1035–1054

    Article  PubMed  CAS  Google Scholar 

  • Armfield, J., Roberts-Thomson, K. and Spencer, A.: 2000, Australia’s Health 2000: The Seventh Biennial Health Report of the Australian Institute of Health and Welfare. Canberra

  • Bellamy W., Takase M., Wakabayashi H., Kawase K., Tomita M. (1992) J. Appl. Bacteriol. 73:472–479

    PubMed  CAS  Google Scholar 

  • Bevins C. L., Zasloff M. (1990) Annu. Rev. Biochem. 59:395–414

    Article  PubMed  CAS  Google Scholar 

  • Boman H. G. (2003) J. Intern. Med. 254:197–215

    Article  PubMed  CAS  Google Scholar 

  • Boman H. G., Hultmark D. (1987) Annu. Rev. Microbiol. 41:103–126

    Article  PubMed  CAS  Google Scholar 

  • Brogden K. A. (2005) Nat. Rev. Microbiol. 3:238–250

    Article  PubMed  CAS  Google Scholar 

  • Buswell C. M., Herlihy Y. M., Lawrence L. M., Mcguiggan J. T., Marsh P. D., Keevil C. W., Leach S. A. (1998) Appl. Environ. Microbiol. 64:733–741

    PubMed  CAS  Google Scholar 

  • Campagna S., Mathot A. G., Fleury Y., Girardet J. M., Gaillard J. L. (2004) J. Dairy Sci. 87:1621–1626

    Article  PubMed  CAS  Google Scholar 

  • Casteels P., Ampe C., Jacobs F., Vaeck M., Tempst P. (1989) EMBO J. 8:2387–2391

    PubMed  CAS  Google Scholar 

  • Christersson C. E., Dunford R. G., Glantz P. O., Baier R. E. (1989) Scand. J. Dent. Res. 97:247–256

    PubMed  CAS  Google Scholar 

  • Clare D. A., Catignani G. L., Swaisgood H. E. (2003) Curr. Pharm. Des. 9:1239–1255

    Article  PubMed  CAS  Google Scholar 

  • Clark D. P., Durell S., Maloy W. L., Zasloff M. (1994) J. Biol. Chem. 269:10849–10855

    PubMed  CAS  Google Scholar 

  • Costerton J. W., Lewandowski Z., Caldwell D. E., Korber D. R., Lappin-Scott H. M. (1995) Annu. Rev. Microbiol. 49:711–745

    Article  PubMed  CAS  Google Scholar 

  • Creamer, L. K. and Harris, D. P.: 1997, in Milk Protein Polymorphism. International Dairy Federation Special Issue, pp. 110–123

  • Cummins D. (1991) J. Clin. Periodontol. 18:455–461

    Article  PubMed  CAS  Google Scholar 

  • Cummins D., Creeth J. E. (1992) J. Dent. Res. 71:1439–1449

    PubMed  CAS  Google Scholar 

  • Cvitkovitch D. G., Li Y. H., Ellen R. P. (2003) J. Clin. Invest. 112:1626–1632

    Article  PubMed  CAS  Google Scholar 

  • Dashper S. G., Reynolds E. C. (1990) J. Bacteriol. 172:556–563

    PubMed  CAS  Google Scholar 

  • Dashper S. G., Reynolds E. C. (1992) J. Dent. Res. 71:1159–1165

    PubMed  CAS  Google Scholar 

  • Dashper S. G., Reynolds E. C. (2000) J. Dent. Res. 79:90–96

    PubMed  CAS  Google Scholar 

  • Dashper S. G., O’brien-Simpson N. M., Cross K. J., Paolini R. A., Hoffmann B., Catmull D. V., Malkoski M., Reynolds E. C. (2005) Antimicrob. Agents Chemother. 49:2322–2328

    Article  PubMed  CAS  Google Scholar 

  • Eckert R., He J., Yarbrough D. K., Qi F., Anderson M. H., Shi W. (2006a) Antimicrob. Agents Chemother. 50:3651–3657

    PubMed  CAS  Google Scholar 

  • Eckert R., Qi F., Yarbrough D. K., He J., Anderson M. H., Shi W. (2006b) Antimicrob. Agents Chemother. 50:1480–1488

    Article  PubMed  CAS  Google Scholar 

  • Ellen R. P., Lepine G., Nghiem P. M. (1997) Adv. Dent. Res. 11:33–42

    PubMed  CAS  Google Scholar 

  • Farnaud S., Patel A., Odell E. W., Evans R. W. (2004a) FEMS Microbiol. Lett. 238:221–226

    Article  PubMed  CAS  Google Scholar 

  • Farnaud S., Spiller C., Moriarty L. C., Patel A., Gant V., Odell E. W., Evans R. W. (2004b) FEMS Microbiol. Lett. 233:193–199

    Article  PubMed  CAS  Google Scholar 

  • Floris R., Recio I., Berkhout B., Visser S. (2003) Curr. Pharm. Des. 9:1257–1275

    Article  CAS  Google Scholar 

  • Giovannini M. G., Poulter L., Gibson B. W., Williams D. H. (1987) Biochem. J. 243:113–120

    PubMed  CAS  Google Scholar 

  • Goumon Y., Strub J. M., Moniatte M., Nullans G., Poteur L., Hubert P., Van Dorsselaer A., Aunis D., Metz-Boutigue M. H. (1996) Eur. J. Biochem. 235:516–525

    Article  PubMed  CAS  Google Scholar 

  • Hayes M., Ross R. P., Fitzgerald G. F., Hill C., Stanton C. (2006) Appl. Environ. Microbiol. 72:2260–2264

    Article  PubMed  CAS  Google Scholar 

  • Hill R. D., Lahav E., Givol D. (1974) J. Dairy Res. 41:147–153

    PubMed  CAS  Google Scholar 

  • Hope C. K., Wilson M. (2003) J. Microbiol. Methods 54:403–410

    Article  PubMed  CAS  Google Scholar 

  • Hultmark D., Steiner H., Rasmuson T., Boman H. G. (1980) Eur. J. Biochem. 106:7–16

    Article  PubMed  CAS  Google Scholar 

  • Hwang P. M., Vogel H. J. (1998) Biochem. Cell Biol. 76:235–246

    Article  PubMed  CAS  Google Scholar 

  • Kieffer B., Dillmann B., Lefevre J. F., Goumon Y., Aunis D., Metz-Boutigue M. H. (1998) J. Biol. Chem. 273:33517–33523

    Article  PubMed  CAS  Google Scholar 

  • Kolenbrander P. E., Ganeshkumar N., Cassels F. J., Hughes C. V. (1993) FASEB J. 7:406–413

    PubMed  CAS  Google Scholar 

  • Lahov E., Regelson W. (1996) Food Chem. Toxicol. 34:131–145

    Article  PubMed  CAS  Google Scholar 

  • Lai R., Lomas L. O., Jonczy J., Turner P. C., Rees H. H. (2004) Biochem. J. 379:681–685

    Article  PubMed  CAS  Google Scholar 

  • Lee W. J., Brey P. T. (1994) Anal. Biochem. 217:231–235

    Article  PubMed  CAS  Google Scholar 

  • Loë H., Theilade E., Jensen S. B. (1965) J. Periodontol. 36:177–187

    PubMed  Google Scholar 

  • Loesche W. J. (1986) Microbiol. Rev. 50:353–380

    PubMed  CAS  Google Scholar 

  • Malin E. L., Alaimo M. H., Brown E. M., Aramini J. M., Germann M. W., Farrell H. M. Jr., Mcsweeney P. L., Fox P. F. (2001) J. Protein Chem. 20:391–404

    Article  PubMed  CAS  Google Scholar 

  • Malkoski M., Dashper S. G., O’brien-Simpson N. M., Talbo G. H., Macris M., Cross K. J., Reynolds E. C. (2001) Antimicrob. Agents Chemother. 45:2309–2315

    Article  PubMed  CAS  Google Scholar 

  • Marsh P. D. (1991) Newsl. Int. Acad. Periodontol. 1:4–5

    PubMed  CAS  Google Scholar 

  • Marsh P. D. (2003) Oral Dis. 9(Suppl 1):16–22

    Article  PubMed  Google Scholar 

  • Maruniak J., Clark W. B., Walker C. B., Magnusson I., Marks R. G., Taylor M., Clouser B. (1992) J. Clin. Periodontol. 19:19–23

    Article  PubMed  CAS  Google Scholar 

  • Matin M. A., Otani H. (2002) J. Dairy Res. 69:329–334

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki K., Murase O., Fujii N., Miyajima K. (1995) Biochemistry 34:6521–6526

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki K., Murase O., Tokuda H., Funakoshi S., Fujii N., Miyajima K. (1994) Biochemistry 33:3342–3349

    Article  PubMed  CAS  Google Scholar 

  • McBain A. J., Bartolo R. G., Catrenich C. E., Charbonneau D., Ledder R. G., Gilbert P. (2003) Appl. Environ. Microbiol. 69:4770–4776

    Article  PubMed  CAS  Google Scholar 

  • Minikiewicz P., Slangen C. J., Lagerwerf F. M., Haverkamp J., Rollema H. S., Visser S. (1996) J. Chromatogr. A 743:123–135

    Article  PubMed  CAS  Google Scholar 

  • Moore L. V., Moore W. E., Cato E. P., Smibert R. M., Burmeister J. A., Best A. M., Ranney R. R. (1987) J. Dent. Res. 66:989–995

    PubMed  CAS  Google Scholar 

  • Mor A. (2003) Peptides 24:1645

    Article  PubMed  CAS  Google Scholar 

  • Neeser J. R., Chambaz A., Del Vedovo S., Prigent M. J., Guggenheim B. (1988) Infect. Immun. 56:3201–3208

    PubMed  CAS  Google Scholar 

  • Nguyen L. T., Schibli D. J., Vogel H. J. (2005) J. Pept. Sci. 11:379–389

    Article  PubMed  CAS  Google Scholar 

  • Oppermann R. V., Rolla G., Johansen J. R., Assev S. (1980) Scand. J. Dent. Res. 88:389–396

    PubMed  CAS  Google Scholar 

  • Orsi N. (2004) Biometals 17:189–196

    Article  PubMed  CAS  Google Scholar 

  • Palmer R. J. Jr., Gordon S. M., Cisar J. O., Kolenbrander P. E. (2003) J. Bacteriol. 185:3400–3409

    Article  PubMed  CAS  Google Scholar 

  • Park Y., Lee D. G., Jang S. H., Woo E. R., Jeong H. G., Choi C. H., Hahm K. S. (2003) Biochim. Biophys. Acta 1645:172–182

    PubMed  CAS  Google Scholar 

  • Pellegrini A., Dettling C., Thomas U., Hunziker P. (2001) Biochim. Biophys. Acta 1526:131–140

    PubMed  CAS  Google Scholar 

  • Pellegrini A., Thomas U., Bramaz N., Hunziker P., Von Fellenberg R. (1999) Biochim. Biophys. Acta 1426:439–448

    PubMed  CAS  Google Scholar 

  • Peters, A. C. and Wimpenny, J. W. T.: 1988, Biotechnol. Bioeng. 32, 263–270

    Google Scholar 

  • Phan T. N., Buckner T., Sheng J., Baldeck J. D., Marquis R. E. (2004) Oral Microbiol. Immunol. 19:31–38

    Article  PubMed  CAS  Google Scholar 

  • Plowman J. E., Creamer L. K., Liddell M. J., Cross J. J. (1997) J. Dairy Res. 64:377–397

    Article  PubMed  CAS  Google Scholar 

  • Recio I., Visser S. (1999) Biochim. Biophys. Acta 1428:314–326

    PubMed  CAS  Google Scholar 

  • Reynolds E. C. (1997) J. Dent. Res. 76:1587–1595

    PubMed  CAS  Google Scholar 

  • Reynolds E. C. (1998) Spec. Care Dentist 18:8–16

    Article  PubMed  CAS  Google Scholar 

  • Rinaldi A. C., Mangoni M. L., Rufo A., Luzi C., Barra D., Zhao H., Kinnunen P. K., Bozzi A., Di Giulio A., Simmaco M. (2002) Biochem. J. 368:91–100

    Article  PubMed  CAS  Google Scholar 

  • Romeo D., Skerlavaj B., Bolognesi M., Gennaro R. (1988) J. Biol. Chem. 263:9573–9575

    PubMed  CAS  Google Scholar 

  • Saito T., Itoh T. (1992) J. Dairy Sci. 75:1768–1774

    Article  PubMed  CAS  Google Scholar 

  • Sauer K., Camper A. K. (2001) J. Bacteriol. 183:6579–6589

    Article  PubMed  CAS  Google Scholar 

  • Schupbach P., Neeser J. R., Golliard M., Rouvet M., Guggenheim B. (1996) J. Dent. Res. 75:1779–1788

    PubMed  CAS  Google Scholar 

  • Shapiro S., Giertsen E., Guggenheim B. (2002) Caries Res. 36:93–100

    Article  PubMed  CAS  Google Scholar 

  • Shu M., Browngardt C. M., Chen Y. Y., Burne R. A. (2003) Infect. Immun. 71:7188–7192

    Article  PubMed  CAS  Google Scholar 

  • Simmaco M., Barra D., Chiarini F., Noviello L., Melchiorri P., Kreil G., Richter K. (1991) Eur. J. Biochem. 199:217–222

    Article  PubMed  CAS  Google Scholar 

  • Sitaram N., Nagaraj R. (1999) Biochim. Biophys. Acta 1462:29–54

    Article  PubMed  CAS  Google Scholar 

  • Socransky S. S., Haffajee A. D., Cugini M. A., Smith C., Kent R. L. Jr. (1998) J. Clin. Periodontol. 25:134–144

    Article  PubMed  CAS  Google Scholar 

  • Spencer A. J. (1985) Commun. Dent. Health 2:277–283

    CAS  Google Scholar 

  • Spencer D. E. (2004) J. Calif. Dent. Assoc. 32:663–664

    PubMed  Google Scholar 

  • Stickler D., Morris N., Moreno M. C., Sabbuba N. (1998) Eur. J. Clin. Microbiol. Infect. Dis. 17:649–652

    Article  PubMed  CAS  Google Scholar 

  • Strub J. M., Garcia-Sablone P., Lonning K., Taupenot L., Hubert P., Van Dorsselaer A., Aunis D., Metz-Boutigue M. H. (1995) Eur. J. Biochem. 229:356–368

    Article  PubMed  CAS  Google Scholar 

  • Svedberg J., De Haas J., Leimenstoll G., Paul F., Teschemacher H. (1985) Peptides 6:825–830

    Article  PubMed  CAS  Google Scholar 

  • Svensater G., Welin J., Wilkins J. C., Beighton D., Hamilton I. R. (2001) FEMS Microbiol. Lett. 205:139–146

    Article  PubMed  CAS  Google Scholar 

  • Talbo G. H., Suckau D., Malkoski M., Reynolds E. C. (2001) Peptides 22:1093–1098

    Article  PubMed  CAS  Google Scholar 

  • Tasiemski A., Vandenbulcke F., Mitta G., Lemoine J., Lefebvre C., Sautiere P. E., Salzet M. (2004) J. Biol. Chem. 279:30973–30982

    Article  PubMed  CAS  Google Scholar 

  • Teughels W., Van Assche N., Sliepen I., Quirynen M. (2006) Clin. Oral Implants Res. 17(Suppl 2):68–81

    Article  PubMed  Google Scholar 

  • Tomita M., Bellamy W., Takase M., Yamauchi K., Wakabayashi H., Kawase K. (1991) J. Dairy Sci. 74:4137–4142

    Article  PubMed  CAS  Google Scholar 

  • Ulvatne H., Samuelsen O., Haukland H. H., Kramer M., Vorland L. H. (2004) FEMS Microbiol. Lett. 237:377–384

    PubMed  CAS  Google Scholar 

  • Vacca-Smith A. M., Van Wuyckhuyse B. C., Tabak L. A., Bowen W. H. (1994) Arch. Oral Biol. 39:1063–1069

    Article  PubMed  CAS  Google Scholar 

  • Van Der Kraan M. I., Groenink J., Nazmi K., Veerman E. C., Bolscher J. G., Nieuw Amerongen A. V. (2004) Peptides 25:177–183

    Article  PubMed  CAS  Google Scholar 

  • Vanhoye D., Bruston F., Nicolas P., Amiche M. (2003) Eur. J. Biochem. 270:2068–2081

    Article  PubMed  CAS  Google Scholar 

  • Weinberg A., Krisanaprakornkit S., Dale B. A. (1998) Crit. Rev. Oral Biol. Med. 9:399–414

    Article  PubMed  CAS  Google Scholar 

  • Wilson M. (1996) J. Med. Microbiol. 44:79–87

    Article  PubMed  CAS  Google Scholar 

  • Zanetti M., Storici P., Tossi A., Scocchi M., Gennaro R. (1994) J. Biol. Chem. 269:7855–7858

    PubMed  CAS  Google Scholar 

  • Zasloff M. (1987) Proc. Natl. Acad. Sci. USA 84:5449–5453

    Article  PubMed  CAS  Google Scholar 

  • Zucht H. D., Raida M., Adermann K., Magert H. J., Forssmann W. G. (1995) FEBS Lett. 372:185–188

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Keith Cross, Neil O’Brien-Simpson, Rita Paolini, Deanne Catmull, Gitti Hoffmann and Marina Malkoski for their contributions to the research. Parts of this research were funded by the CRC for Oral Health Science, Recaldent Pty Ltd. and the Dairy Research and Development Corporation (Australia).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eric C. Reynolds.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dashper, S.G., Liu, S.W. & Reynolds, E.C. Antimicrobial Peptides and their Potential as Oral Therapeutic Agents. Int J Pept Res Ther 13, 505–516 (2007). https://doi.org/10.1007/s10989-007-9094-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-007-9094-z

Keywords

Navigation