Background/Aims:Streptococcus mutans, the major etiological agent of dental caries, has a measurable impact on domestic and global health care costs. Though persistent in the oral cavity despite conventional oral hygiene, S. mutans can be excluded from intact oral biofilms through competitive exclusion by other microorganisms. This suggests that therapies capable of selectively eliminating S. mutans while limiting the damage to the normal oral flora might be effective long-term interventions to fight cariogenesis. To meet this challenge, we designed C16G2, a novel synthetic specifically targeted antimicrobial peptide with specificity for S. mutans. C16G2 consists of a S. mutans-selective ‘targeting region’ comprised of a fragment from S. mutans competence stimulation peptide (CSP) conjoined to a ‘killing region’ consisting of a broad-spectrum antimicrobial peptide (G2). In vitro studies have indicated that C16G2 has robust efficacy and selectivity for S. mutans, and not other oral bacteria, and affects targeted bacteria within seconds of contact. Methods: In the present study, we evaluated C16G2 for clinical utility in vitro, followed by a pilot efficacy study to examine the impact of a 0.04% (w/v) C16G2 rinse in an intra-oral remineralization/demineralization model. Results and Conclusions: C16G2 rinse usage was associated with reductions in plaque and salivary S. mutans, lactic acid production, and enamel demineralization. The impact on total plaque bacteria was minimal. These results suggest that C16G2 is effective against S. mutans in vivo and should be evaluated further in the clinic.

Keywords:
Antimicrobial, Antimicrobial peptide, Caries, Demineralization, Dental plaque, Lactic acid, Mouth rinse, Oral therapeutic, Selective antibiotic, Selective therapeutic
1.
Anderson MH, Shi W: A probiotic approach to caries management. Pediatr Dent 2006;28:151–153; discussion 192–198.
2.
Anonymous: National health expenditure projections 2008–2018; in Services USCfMaM (ed). Office of the Actuary, 2008.
3.
Beighton D: The complex oral microflora of high-risk individuals and groups and its role in the caries process. Community Dent Oral Epidemiol 2005;33:248–255.
4.
Blondelle SE, Simpkins LR, Perez-Paya E, Houghten RA: Influence of tryptophan residues on melittin’s hemolytic activity. Biochim Biophys Acta 1993;1202:331–336.
5.
Carounanidy U, Sathyanarayanan R: Dental caries: A complete changeover, part iii: Changeover in the treatment decisions and treatments. J Conserv Dent 2010;13:209–217.
6.
Corby PM, Lyons-Weiler J, Bretz WA, Hart TC, Aas JA, Boumenna T, Goss J, Corby AL, Junior HM, Weyant RJ, Paster BJ: Microbial risk indicators of early childhood caries. J Clin Microbiol 2005;43:5753–5759.
7.
Damen JJ, Buijs MJ, ten Cate JM: Acidogenicity of buccal plaque after a single rinse with amine fluoride-stannous fluoride mouthrinse solution. Caries Res 2002;36:53–57.
8.
Dickinson DP: Cysteine peptidases of mammals: Their biological roles and potential effects in the oral cavity and other tissues in health and disease. Crit Rev Oral Biol Med 2002;13:238–275.
9.
Eckert R, He J, Yarbrough DK, Qi F, Anderson MH, Shi W: Targeted killing of Streptococcus mutans by a pheromone-guided ‘smart’ antimicrobial peptide. Antimicrob Agents Chemother 2006a;50:3651–3657.
10.
Eckert R, Qi F, Yarbrough DK, He J, Anderson MH, Shi W: Adding selectivity to antimicrobial peptides: Rational design of a multidomain peptide against Pseudomonas spp. Antimicrob Agents Chemother 2006b;50:1480–1488.
11.
Evans CA, Kleinman DV: The surgeon general’s report on America’s oral health: Opportunities for the dental profession. J Am Dent Assoc 2000;131:1721–1728.
12.
Fennell JF, Shipman WH, Cole LJ: Antibacterial action of a bee venom fraction (melittin) against a penicillin-resistant staphylococcus and other microorganisms. USNRDL-TR- 67-101. Res Dev Tech Rep 1967:1–13.
13.
Gerardu VA, Buijs M, van Loveren C, Ten Cate JM: Plaque formation and lactic acid production after the use of amine fluoride/stannous fluoride mouthrinse. Eur J Oral Sci 2007;115:148–152.
14.
Gobor T, Corol G, Ferreira LE, Rymovicz AU, Rosa RT, Campelo PM, Rosa EA: Proposal of protocols using D-glutamine to optimize the 2,3-bis(2-methoxy-4-nitro-5-sulfophenly)-5-[(phenylamino) carbonyl]-2h-tetrazolium hydroxide (XTT) assay for indirect estimation of microbial loads in biofilms of medical importance. J Microbiol Methods 2011;84:299–306.
15.
Gu F, Lux R, Anderson MH, del Aguila MA, Wolinsky L, Hume WR, Shi W: Analyses of Streptococcus mutans in saliva with species-specific monoclonal antibodies. Hybrid Hybridomics 2002;21:225–232.
16.
He J, Yarbrough DK, Kreth J, Anderson MH, Shi W, Eckert R: Systematic approach to optimizing specifically targeted antimicrobial peptides against Streptococcus mutans. Antimicrob Agents Chemother 2010;54:2143–2151.
17.
He X, Lux R, Kuramitsu HK, Anderson MH, Shi W: Achieving probiotic effects via modulating oral microbial ecology. Adv Dent Res 2009;21:53–56.
18.
Izco JM, Tormo M, Jimenez-Flores R: Rapid simultaneous determination of organic acids, free amino acids, and lactose in cheese by capillary electrophoresis. J Dairy Sci 2002;85:2122–2129.
19.
Kaplan CW, Sim JH, Shah KR, Kolesnikova A, Shi W, Eckert R: Selective membrane disruption: The mode of action of C16G2, a specifically targeted antimicrobial peptide. Antimicrob Agents Chemother 2011;55:3446–3452.
20.
Keene HJ, Shklair IL: Relationship of Streptococcus mutans carrier status to the development of carious lesions in initially cariesfree recruits. J Dent Res 1974;53:1295.
21.
Keyes PH, White CL: Dental caries in the molar teeth of rats. III. Bio-assay of sodium fluoride and sodium lauroyl sarcosinate as caries-inhibitory agents. J Am Dent Assoc 1959;58:43–55.
22.
Koch G, Petersson LG, Ryden H: Effect of fluoride varnish (Duraphat) treatment every six months compared with weekly mouthrinses with 0.2 per cent NaF solution on dental caries. Swed Dent J 1979;3:39–44.
23.
Li LN, Guo LH, Lux R, Eckert R, Yarbrough D, He J, Anderson M, Shi WY: Targeted antimicrobial therapy against Streptococcus mutans establishes protective non-cariogenic oral biofilms and reduces subsequent infection. Int J Oral Sci 2010;2:66–73.
24.
Loesche WJ: Role of Streptococcus mutans in human dental decay. Microbiol Rev 1986;50:353–380.
25.
Marsh PD: Microbiology of dental plaque biofilms and their role in oral health and caries. Dent Clin North Am 2010;54:441–454.
26.
Pitanga Fernandes ET, Duarte Vargas AM, Oliveira AC, Camargo da Rosa MA, Dutra Lucas S, Ferreira EFE: Factors related to dental caries in adolescents in southeastern Brazil. Eur J Paediatr Dent 2010;11:165–170.
27.
Sawai MV, Waring AJ, Kearney WR, McCray PB Jr, Forsyth WR, Lehrer RI, Tack BF: Impact of single-residue mutations on the structure and function of ovispirin/novispirin antimicrobial peptides. Protein Eng 2002;15:225–232.
28.
Tanzer JM, Livingston J, Thompson AM: The microbiology of primary dental caries in humans. J Dent Educ 2001;65:1028–1037.
29.
Tom D: Review: Increasing fluoride concentrations in toothpastes improved prevention of dental caries. Arch Dis Child Educ Pract Ed 2011;96:159.
30.
Tong Z, Dong L, Zhou L, Tao R, Ni L: Nisin inhibits dental caries-associated microorganism in vitro. Peptides 2010;31:2003–2008.
31.
Tsang PW, Qi F, Huwig AK, Anderson MH, Wesley D, Shi W: A medical approach to the diagnosis and treatment of dental caries. AHIP Cover 2006;47:38–42.
32.
Vaucher RA, Teixeira ML, Brandelli A: Investigation of the cytotoxicity of antimicrobial peptide p40 on eukaryotic cells. Curr Microbiol 2010;60:1–5.
33.
Vollmer WM, Papas AS, Bader JD, Maupome G, Gullion CM, Hollis JF, Snyder JJ, Fellows JL, Laws RL, White BA: Design of the prevention of adult caries study (PACS): A randomized clinical trial assessing the effect of a chlorhexidine dental coating for the prevention of adult caries. BMC Oral Health 2010;10:23.
34.
Williams MI, Cummins D: The technology behind Colgate Total Advanced Fresh. Compend Contin Educ Dent 2003;24:4–9, quiz 42.
35.
Young DA, Lyon L, Azevedo S: The role of dental hygiene in caries management: A new paradigm. J Dent Hyg 2010;84:121–129.
36.
Zhu WL, Nan YH, Hahm KS, Shin SY: Cell selectivity of an antimicrobial peptide melittin diastereomer with D-amino acid in the leucine zipper sequence. J Biochem Mol Biol 2007;40:1090–1094.
© 2011 S. Karger AG, Basel
2011
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.