Review Article

Streptococcus Mutans-Specific Antimicrobial Peptide C16G2-Mediated Caries Prevention: A Review

Abstract

Oral biofilms are a group of healthy synergistic organisms, that on interplay with the immune system undergo transition and colonize the pathogenic bacteria, leading to various diseases like dental caries, gingivitis, periodontitis and a few systemic conditions. Dental caries being the most common disease of the oral cavity, comprise a heterogeneous group of bacteria that can cause imbalance in the biofilm. Caries prevention has been in research for decades, where antibiotics, chemical biocides and fluoride-antimicrobial approaches have not been adequate for this multifactorial disease. In recent years, the major focus of caries prevention has been shifted to plaque-biofilm modification as an ecological approach that would prevent bacterial colonization. Saliva produces various natural antimicrobial peptides that can regulate biofilm modification. Synthetic production of antimicrobial peptides concentrates on selective elimination and a targeted approach towards cariogenic pathogens, precisely Streptococcus mutans (S. mutans). A search in Medline/PubMed, EBSCO and ScienceDirect databases on C16G2, antimicrobial peptides (AMPs) and S. mutans, using MeSH (Medical Subject Heading) terms was performed and papers published until 2020 were included for further evaluation. A total of eight articles written in English with available full texts were selected based on the search strategy. They included four publications on AMPs against S. mutans and another four articles on AMPs in caries prevention. This review focuses on C16G2 antimicrobial peptide and its potential to modify biofilm and inhibit the targeted bacteria causing dental caries.

1. Band VI, Weiss DS. Mechanisms of Antimicrobial Peptide Resistance in Gram-Negative Bacteria. Antibiotics (Basel). 2015 Mar;4(1):18-41.
2. Niu JY, Yin IX, Wu WKK, Li QL, Mei ML, Chu CH. Antimicrobial peptides for the prevention and treatment of dental caries: A concise review. Arch Oral Biol. 2021 Feb;122:105022.
3. Mwangi J, Hao X, Lai R, Zhang ZY. Antimicrobial peptides: new hope in the war against multidrug resistance. Zool Res. 2019 Nov 18;40(6):488-505.
4. He J, Eckert R, Pharm T, Simanian MD, Hu C, Yarbrough DK, et al. Novel synthetic antimicrobial peptides against Streptococcus mutans. Antimicrob Agents Chemother. 2007 Apr;51(4):1351-8.
5. Mahlapuu M, Håkansson J, Ringstad L, Björn C. Antimicrobial Peptides: An Emerging Category of Therapeutic Agents. Front Cell Infect Microbiol. 2016 Dec 27;6:194.
6. Peters BM, Shirtliff ME, Jabra-Rizk MA. Antimicrobial peptides: primeval molecules or future drugs? PLoS Pathog. 2010 Oct 28;6(10):e1001067.
7. Bahar AA, Ren D. Antimicrobial peptides. Pharmaceuticals (Basel). 2013 Nov 28;6(12):1543-75.
8. Philip N, Suneja B, Walsh LJ. Ecological Approaches to Dental Caries Prevention: Paradigm Shift or Shibboleth? Caries Res. 2018;52(1-2):153-165.
9. Santosh AB, Reddy BV. Oral Mucosal Infections: Insights into Specimen Collection and Medication Management. Dent Clin North Am. 2017 Apr;61(2):283-304.
10. Elías-Boneta AR, Toro MJ, Rivas-Tumanyan S, Rajendra-Santosh AB, Brache M, Collins C JR. Prevalence, Severity, and Risk Factors of Gingival Inflammation in Caribbean Adults: A Multi-City, Cross-Sectional Study. P R Health Sci J. 2018 Jun;37(2):115-123.
11. Tahmourespour A, Kermanshahi RK, Salehi R, Pero NG. Biofilm formation potential of oral streptococci in related to some carbohydrate substrates. Afr. J. Microbiol. Res. 2010 Jun 4;4(11):1051-6.
12. Marsh P, Martin MV, Rogers H, Williams D, Wilson M. Marsh and Martin's Oral Microbiology, 6th ed.; Elsevier: London, UK, 2016.
13. Malanovic N, Lohner K. Antimicrobial Peptides Targeting Gram-Positive Bacteria. Pharmaceuticals (Basel). 2016 Sep 20;9(3):59.
14. Nguyen LT, Haney EF, Vogel HJ. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol. 2011 Sep;29(9):464-72.
15. Sharma S, Sahoo N, Bhunia A. Antimicrobial Peptides and their Pore/Ion Channel Properties in Neutralization of Pathogenic Microbes. Curr Top Med Chem. 2016;16(1):46-53.
16. Yeaman MR, Yount NY. Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev. 2003 Mar;55(1):27-55.
17. Ebenhan T, Gheysens O, Kruger HG, Zeevaart JR, Sathekge MM. Antimicrobial peptides: their role as infection-selective tracers for molecular imaging. Biomed Res Int. 2014;2014:867381.
18. Lai Y, Gallo RL. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 2009 Mar;30(3):131-41.
19. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002 Jan 24;415(6870):389-95.
20. Matsuzaki K. Control of cell selectivity of antimicrobial peptides. Biochim Biophys Acta. 2009 Aug;1788(8):1687-92.
21. He X, Lux R, Kuramitsu HK, Anderson MH, Shi W. Achieving probiotic effects via modulating oral microbial ecology. Adv Dent Res. 2009;21(1):53-6.
22. Eckert R. Road to clinical efficacy: challenges and novel strategies for antimicrobial peptide development. Future Microbiol. 2011 Jun;6(6):635-51.
23. Murugesh J, Sameera A, Aysha S, “STAMPS” Smart therapy against streptococcus mutans: review article. Int J Oral Health Dent 2015;1(2):81-84
24. Dufour D, Barbour A, Chan Y, Cheng M, Rahman T, Thorburn M, et al. Genetic Analysis of Mutacin B-Ny266, a Lantibiotic Active against Caries Pathogens. J Bacteriol. 2020 May 27;202(12):e00762-19.
25. Kokilakanit P, Koontongkaew S, Roytrakul S, Utispan K. A novel non-cytotoxic synthetic peptide, Pug-1, exhibited an antibiofilm effect on Streptococcus mutans adhesion. Lett Appl Microbiol. 2020 Mar;70(3):151-158.
26. Zhong H, Xie Z, Wei H, Zhang S, Song Y, Wang M, et al. Antibacterial and Antibiofilm Activity of Temporin-GHc and Temporin-GHd Against Cariogenic Bacteria, Streptococcus mutans. Front Microbiol. 2019 Dec 11;10:2854.
27. Baker JL, He X, Shi W. Precision Reengineering of the Oral Microbiome for Caries Management. Adv Dent Res. 2019 Nov;30(2):34-39.
28. 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. 2006 Nov;50(11):3651-7.
29. Qiu XQ, Wang H, Lu XF, Zhang J, Li SF, Cheng G, et al. An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria. Nat Biotechnol. 2003 Dec;21(12):1480-5.
30. Krunić J, Stojanović N, Đukić L, Roganović J, Popović B, Simić I, et al. Clinical antibacterial effectiveness and biocompatibility of gaseous ozone after incomplete caries removal. Clin Oral Investig. 2019 Feb;23(2):785-792.
31. Wattanarat O, Makeudom A, Sastraruji T, Piwat S, Tianviwat S, Teanpaisan R, et al. Enhancement of salivary human neutrophil peptide 1-3 levels by probiotic supplementation. BMC Oral Health. 2015 Feb 10;15:19.
32. Martins C, Castro GF, Siqueira MF, Xiao Y, Yamaguti PM, Siqueira WL. Effect of dialyzed saliva on human enamel demineralization. Caries Res. 2013;47(1):56-62.
33. Kelly CG, Younson JS, Hikmat BY, Todryk SM, Czisch M, Haris PI, et al. A synthetic peptide adhesion epitope as a novel antimicrobial agent. Nat Biotechnol. 1999 Jan;17(1):42-7.
34. Becker MR, Paster BJ, Leys EJ, Moeschberger ML, Kenyon SG, Galvin JL, et al. Molecular analysis of bacterial species associated with childhood caries. J Clin Microbiol. 2002 Mar;40(3):1001-9.
35. Anderson MH, Shi W. A probiotic approach to caries management. Pediatr Dent. 2006 Mar-Apr;28(2):151-3; discussion 192-8.
36. 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 May;54(5):2143-51.
37. Eckert R, Sullivan R, Shi W. Targeted antimicrobial treatment to re-establish a healthy microbial flora for long-term protection. Adv Dent Res. 2012 Sep;24(2):94-7.
38. Qi F, Kreth J, Lévesque CM, Kay O, Mair RW, Shi W, et al. Peptide pheromone induced cell death of Streptococcus mutans. FEMS Microbiol Lett. 2005 Oct 15;251(2):321-6.
39. Hancock RE, Lehrer R. Cationic peptides: a new source of antibiotics. Trends Biotechnol. 1998 Feb;16(2):82-8.
40. Kaplan CW, Sim JH, Shah KR, Kolesnikova-Kaplan A, Shi W, Eckert R. Selective membrane disruption: mode of action of C16G2, a specifically targeted antimicrobial peptide. Antimicrob Agents
Chemother. 2011 Jul;55(7):3446-52.
41. 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(5):415-28.
42. Guo L, McLean JS, Yang Y, Eckert R, Kaplan CW, Kyme P, et al. Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology. Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):7569-74.
43. Li LN, Guo LH, Lux R, Eckert R, Yarbrough D, He J, et al. Targeted antimicrobial therapy against Streptococcus mutans establishes protective non-cariogenic oral biofilms and reduces subsequent infection. Int J Oral Sci. 2010 Jun;2(2):66-73.
IssueVol 19 (Continuously Published Article-Based) QRcode
SectionReview Article
DOI https://doi.org/10.18502/fid.v19i17.9963
Keywords
Antimicrobial Peptides Streptococcus mutans Mouthwashes Dental Caries Anti-Bacterial Agents

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
NAMBURU JR, RAJENDRA SANTOSH AB, POOSARLA CS, MANTHAPURI S, PINNAKA M, BADDAM VRR. Streptococcus Mutans-Specific Antimicrobial Peptide C16G2-Mediated Caries Prevention: A Review. Front Dent. 2022;19.