Comparison of antibacterial and antifungal efficacy of self-assembling peptide P11-4 with different remineralization agents: an in-vitro microbiological study

Background: The aim of this study is to evaluate the effect of self-assembling peptide (SAP) P11-4 on the Streptococcus mutans American Type Culture Collection (ATCC) 10449, Lactobacillus casei ATCC 11578 and Candida albicans ATCC 60193 and to compare the antibacterial and antifungal activity with different remineralisation agents. Methods: This in-vitro microbiological study was performed with five independent groups (G1. Chlorhexidine Gel (Best Dental, Istanbul, Turkey), G2. Profluorid Varnish® (VOCO GmbH, Cuxhaven, Germany), G3. Curodont™ Protect (Credentis AG, Windisch, Switzerland), G4. Tooth Mousse™ (GC Corporation, Tokyo, Japan) and G5. MI Paste Plus (GC Corporation, Tokyo, Japan)). The antimicrobial activities of the samples were evaluated according to 24-hour time kill assay against S. mutans, L. casei and C. albicans. Results: The control, Group 1—Chlorhexidine gel, had the strongest antibacterial activity against all of the tested microorganisms. The results showed that Group 4—Tooth Mousse™ was the most effective remineralization agent with the best antimicrobial activity against S. mutans and C. albicans, followed behind respectively with Group 5—MI Paste Plus, Group 3—Curodont™ Protect, and Group 2—Profluorid Varnish®. Group 5—MI Paste Plus demonstrated the most effective antibacterial activity against L. casei. Group 4—Tooth Mousse™, Group 2—Profluorid Varnish®, and Group 3—Curodont™ Protect were afterwards in order. Conclusions: SAP P11-4 can be used as an antimicrobial agent to prevent opportunistic fungal infections as well as to prevent and halt the progression of incipient lesions.

Self-assembling peptide; Tooth remineralization; Sodium fluoride; Casein Phosphopeptide-amorphous calcium phosphate; Antibacterial; Antifungal

[1] Pitts NB, Zero DT, Marsh PD, Ekstrand K, Weintraub JA, Ramos-Gomez F, et al. Dental caries. Nature Reviews Disease Primers. 2017; 3: 17030.

[2] Machiulskiene V, Campus G, Carvalho JC, Dige I, Ekstrand KR, Jablonski-Momeni A, et al. Terminology of dental caries and dental caries management: consensus report of a workshop organized by ORCA and cariology research group of IADR. Caries Research. 2020; 54: 7–14.

[3] Selwitz RH, Ismail AI, Pitts NB. Dental caries. The Lancet. 2007; 369: 51–59.

[4] Ten Cate JM, Buzalaf MAR. Fluoride mode of action: once there was an observant dentist... Journal of Dental Research. 2019; 98: 725–730.

[5] Reynolds EC. Casein phosphopeptide-amorphous calcium phosphate: the scientific evidence. Advances in Dental Research. 2009; 21: 21–29.

[6] Keskin G, Güler Ç. Casein phosphopeptide amorphous calicum phosphate in dentistry. Journal of Dental Faculty of Atatürk University. 2012; 23: 261–268. (In Turkish)

[7] Cross KJ, Huq NL, Stanton DP, Sum M, Reynolds EC. NMR studies of a novel calcium, phosphate and fluoride delivery vehicle-αS1-casein(59–79) by stabilized amorphous calcium fluoride phosphate nanocomplexes. Biomaterials. 2004; 25: 5061–5069.

[8] Kirkham J, Brookes SJ, Shore RC, Wood SR, Smith DA, Zhang J, et al. Physico-chemical properties of crystal surfaces in matrix-mineral interactions during mammalian biomineralisation. Current Opinion in Colloid & Interface Science. 2002; 7: 124–132.

[9] Bonchev A, Vasileva R, Dyulgerova E, Yantcheva S. Self-assembling Peptide P11‑4: a biomimetic agent for enamel remineralization. International Journal of Peptide Research and Therapeutics. 2021; 27: 899–907.

[10] Aggeli A, Bell M, Boden N, Keen JN, Knowles PF, McLeish TC, et al. Responsive gels formed by the spontaneous self-assembly of peptides in to polymeric ß-sheet tapes. Nature. 1997; 386: 259–262.

[11] Aggeli A, Bell M, Boden N, Carrick LM, Strong AE. Self-assembling peptide polyelectrolyte β-sheet complexes form nematic hydrogels. Angewandte Chemie. 2003; 42: 5603–5606.

[12] Brunton PA, Davies RP, Burke JL, Smith A, Aggeli A, Brookes SJ, et al. Treatment of early caries lesions using biomimetic self-assembling peptides—a clinical safety trial. British Dental Journal. 2013; 215: E6.

[13] Kind L, Stevanovic S, Wuttig S, Wimberger S, Hofer J, Müller B, et al. Biomimetic remineralization of carious lesions by self-assembling peptide. Journal of Dental Research. 2017; 96: 790–797.

[14] Harper DS, Loesche WJ. Growth and acid tolerance of human dental plaque bacteria. Archives of Oral Biology. 1984; 29: 843–848.

[15] Tanzer JM, Livingston J, Thompson AM. The microbiology of primary dental caries in humans. Journal of Dental Education. 2001; 65: 1028–1037.

[16] Banas JA. Virulence properties of steptococcus mutans. Frontiers in Bioscience. 2004; 9: 1267–1277.

[17] Van Houte J, Gibbons RJ, Pulkkinen AJ. Ecology of human oral lactobacilli. Infection and Immunity.1972; 6: 723–729.

[18] Loesche WJ, Syed SA. The predominant cultivable flora of carious plaque and carious dentine. Caries Research. 1973; 7: 201–216.

[19] Lu Y, Lin Y, Li M, He J. Roles of Streptococcus mutans-candida albicans interaction in early childhood caries: a literature review. Frontiers in Cellular and Infection Microbiology. 2023; 13: 1151532.

[20] Gunaratnam G, Dudek J, Jung P, Becker SL, Jacobs K, Bischoff M, et al. Quantification of the adhesion strength of Candida albicans to tooth enamel. Microorganisms. 2021; 9: 2213.

[21] Kundu R, Tripathi AM, Jaiswal JN, Ghoshal U, Palit M, Khanduja S. Effect of fixed space maintainers and removable appliances on oral microflora in children: an in vivo study. Journal of Indian Society of Pedodontics and Preventive Dentistry. 2016; 34: 3–9.

[22] Chandran V, Smitha M, Azher U, Paul ST. Comparative evaluation of antimicrobial efficacy of silver diamine fluoride and curodonttm protect remineralizing agents on streptococcus mutans: an in vitro microbiological study. Journal of South Asian Association of Pediatric Dentistry. 2022; 5: 147–151.

[23] Gayas Z, Azher U, Paul ST, Selvan A, Reddy CD, Raghu D, et al. Comparative evaluation of antimicrobial efficacy of fluoride‑based and self-assembling peptide P11-4-based tooth remineralization agents on streptococcus mutans: a microbiological study. Contemporary Clinical Dentistry. 2023; 14: 141–144.

[24] İlgen G, Çoğulu D, Uçan E, Uzel A. Evaluation of the etiological factors of black tooth stain in children. The Journal of Pediatric Research. 2023; 10: 216–221.

[25] Özyildiz F, Uzel A, Hazar AS, Guden M, Olmez S, Aras I, et al. Photocatalytic antimicrobial effect of TiO2 anatase thin-film-coated orthodontic arch wires on 3 oral pathogens. Turkish Journal of Biology. 2014; 38: 289–295.

[26] Forssten SD, Björklund M, Ouwehand AC. Streptococcus mutans, caries and simulation models. Nutrients. 2010; 2: 290–298.

[27] Bratthal D, Carlsson P. Clinical microbiology of saliva. In Tenovuo JO (ed.) Human saliva: clinical chemistry and microbiology vol II (pp. 203–241). 1st edn. CRC Press: Florida. 1989.

[28] Guo L, Shi W. Salivary biomarkers for caries risk assessment. Journal of the California Dental Association. 2013; 41: 107–118.

[29] Badet C, Thebaud NB. Ecology of lactobacilli in the oral cavity: a review of literature. The Open Microbiology Journal. 2008; 2: 38–48.

[30] Ribeiro LG, Hashizume LN, Maltz M. The effect of different formulations of chlorhexidine in reducing levels of mutans streptococci in the oral cavity: a systematic review of the literature. Journal of Dentistry. 2007; 35: 359–370.

[31] Walsh T, Oliveira-Neto JM, Moore D. Chlorhexidine treatment for the prevention of dental caries in children and adolescents. Cochrane Database of Systematic Reviews. 2015; 2015: CD008457.

[32] Pinar Erdem A, Sepet E, Kulekci G, Trosola SC, Guven Y. Effects of two fluoride varnishes and one fluoride/chlorhexidine varnish on streptococcus mutans and Streptococcus sobrinus biofilm formation in vitro. International Journal of Medical Sciences. 2012; 9: 129–136.

[33] Philip N, Leishman SJ, Bandara HMHN, Healey DL, Walsh LJ. Randomized controlled study to evaluate microbial ecological effects of CPP-ACP and cranberry on dental plaque. JDR Clinical & Translational Research. 2020; 5: 118–126.

[34] Al-Haj Ali SN, Al-Ogayyel S, Farah RI. Antibacterial efficacy of silver diamine fluoride compared to casein phosphopeptide-amorphous calcium phosphate against streptococcus mutans in a biofilm caries model. Pesquisa Brasileira em Odontopediatria e Clínica Integrada. 2023; 23: e220148.(In Portuguese)

[35] Monica M, Fauziah E, Budiardjo SB, Suharsini M. Antifungal effectiveness of virgin coconut oil mousse against Candida albicans biofilm in children with early childhood caries. Journal of Stomatology. 2018; 71: 259–262.

[36] Aparna BK, Yashoda R, Puranik MP. Remineralization of early enamel caries lesions using self-assembling peptides P11-4: systematic review and meta-analysis. Journal of Oral Biology and Craniofacial Research. 2022; 12: 324–331.

[37] Hong W, Zhao Y, Guo Y, Huang C, Qiu P, Zhu J, et al. Correction: “PEGylated self-assembled nano-bacitracin A: probing the antibacterial mechanism and real-time tracing of target delivery in vivo”. ACS Applied Materials & Interfaces. 2019; 11: 7635.

[38] Nguyen LT, Haney EF, Vogel HJ. The expanding scope of antimicrobial peptide structures and their modes of action. Trends in Biotechnology. 2011; 29: 464–472.

[39] Magalhães GAP, Fraga MAA, de Souza Araújo IJ, Pacheco RR, Correr AB, Puppin-Rontani RM. Effect of a self-assembly peptide on surface roughness and hardness of bleached enamel. Journal of Functional Biomaterials. 2022; 13: 79.

[40] Eslemez Topcu E, Şahin O, Köroğlu A, Cömert F, Yilmaz B. Surface roughness and Streptococcus mutans adhesion on surface sealant agent coupled interim crown materials after dynamic loading. BMC Oral Health. 2022; 22: 299.