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Antimicrobial and antibiofilm effects of abietic acid on cariogenic Streptococcus mutans

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Abstract

Dental caries is a type of oral microbiome dysbiosis and biofilm infection that affects oral and systemic conditions. For healthy life expectancy, natural bacteriostatic products are ideal for daily and lifetime use as anti-oral infection agents. This study aimed to evaluate the inhibitory effects of abietic acid, a diterpene derived from pine rosin, on the in vitro growth of cariogenic bacterial species, Streptococcus mutans. The effective minimum inhibitory concentration of abietic acid was determined through observation of S. mutans growth, acidification, and biofilm formation. The inhibitory effects of abietic acid on the bacterial membrane were investigated through the use of in situ viability analysis and scanning electron microscopic analysis. Cytotoxicity of abietic acid was also examined in the context of several human cell lines using tetrazolium reduction assay. Abietic acid was found to inhibit key bacterial growth hallmarks such as colony forming ability, adenosine triphosphate activity (both planktonic and biofilm), acid production, and biofilm formation. Abietic acid was identified as bacteriostatic, and this compound caused minimal damage to the bacterial membrane. This action was different from that of povidone-iodine or cetylpyridinium chloride. Additionally, abietic acid was significantly less cytotoxic compared to povidone-iodine, and it exerted lower toxicity towards epithelial cells and fibroblasts compared to that against monocytic cells. These data suggest that abietic acid may prove useful as an antibacterial and antibiofilm agent for controlling S. mutans infection.

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References

  1. Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol. 2005;43:5721–32.

    PubMed  PubMed Central  Google Scholar 

  2. Paster BJ, Olsen I, Aas JA, Dewhirst FE. The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontology. 2000;2006(42):80–7.

    Google Scholar 

  3. Cisar JO, Kolenbrander PE, McIntire FC. Specificity of coaggregation reactions between human oral Streptococci and strains of Actinomyces viscosus or Actinomyces naeslundii. Infect Immun. 1979;24:742–52.

    PubMed  PubMed Central  Google Scholar 

  4. Simón-Soro A, Mira A. Solving the etiology of dental caries. Trends Microbiol. 2015;23(2):76–82.

    PubMed  Google Scholar 

  5. Bowen WH, Koo H. Biology of Streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms. Caries Res. 2011;45(1):69–86.

    PubMed  PubMed Central  Google Scholar 

  6. Metwalli KH, Khan SA, Krom BP, Jabra-Rizk MA. Streptococcus mutans, Candida albicans, and the human mouth: a sticky situation. PLoS Pathog. 2013;9(10):e1003616.

    PubMed  PubMed Central  Google Scholar 

  7. Nakano K, Hokamura K, Taniguchi N, Wada K, Kudo C, Nomura R, Kojima A, Naka S, Muranaka Y, Thura M, Nakajima A, Masuda K, Nakagawa I, Speziale P, Shimada N, Amano A, Kamisaki Y, Tanaka T, Umemura K, Ooshima T. The collagen-binding protein of Streptococcus mutans is involved in haemorrhagic stroke. Nat Commun. 2011;2:485.

    PubMed  PubMed Central  Google Scholar 

  8. Kojima A, Nakano K, Wada K, Takahashi H, Katayama K, Yoneda M, Higurashi T, Nomura R, Hokamura K, Muranaka Y, Matsuhashi N, Umemura K, Kamisaki Y, Nakajima A, Ooshima T. Infection of specific strains of Streptococcus mutans, oral bacteria, confers a risk of ulcerative colitis. Sci Rep. 2012;2:332.

    PubMed  PubMed Central  Google Scholar 

  9. Watanabe I, Kuriyama N, Miyatani F, Nomura R, Naka S, Nakano K, Ihara M, Iwai K, Matsui D, Ozaki E, Koyama T, Nishigaki M, Yamamoto T, Tamura A, Mizuno T, Akazawa K, Takada A, Takeda K, Yamada K, Nakagawa M, Tanaka T, Kanamura N, Friedland RP, Watanabe Y. Oral Cnm-positive Streptococcus Mutans expressing collagen binding activity is a risk factor for cerebral microbleeds and cognitive impairment. Sci Rep. 2016;9(6):38561.

    Google Scholar 

  10. Fung-Tomc J. Correlation of in vitro and in vivo resistance development to antimicrobial agents. Antimicrob Newslett. 1990;7:17–24.

    Google Scholar 

  11. Pallasch TJ, Slots J. Antibiotic prophylaxis and the medically compromised host. Periodontology. 2000;1996(10):107–38.

    Google Scholar 

  12. Scully C, El-Kabir M, Samaranayake LP. Candida and oral candidosis: a review. Crit Rev Oral Biol Med. 1994;5:125–57.

    PubMed  Google Scholar 

  13. Tacconelli E, De Angelis G, Cataldo MA, Pozzi E, Cauda R. Does antibiotic exposure increase the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis. J Antimicrob Chemother. 2008;61:26–38.

    PubMed  Google Scholar 

  14. Brecx M, Netuschil L, Hoffmann T. How to select the right mouthrinses in periodontal prevention and therapy. Part II. Clinical use and recommendations. Int J Dent Hyg. 2003;1(4):188–94.

    PubMed  Google Scholar 

  15. Bigliardi PL, Alsagoff SAL, El-Kafrawi HY, Pyon JK, Wa CTC, Villa MA. Povidone iodine in wound healing: a review of current concepts and practices. Int J Surg. 2017;44:260–8.

    PubMed  Google Scholar 

  16. Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis. 2011;11(11):845–54.

    PubMed  Google Scholar 

  17. Addy M, Wright R. Comparison of the in vivo and in vitro antibacterial properties of providone iodine and chlorhexidine gluconate mouthrinses. J Clin Periodontol. 1978;5(3):198–205.

    PubMed  Google Scholar 

  18. Jones CG. Chlorhexidine: is it still the gold standard? Periodontology 2000. 1997;15:55–62.

    PubMed  Google Scholar 

  19. Krautheim AB, Jermann TH, Bircher AJ. Chlorhexidine anaphylaxis: case report and review of the literature. Contact Dermat. 2004;50(3):113–6.

    Google Scholar 

  20. Aremu OS, Gopaul K, Kadam P, Singh M, Mocktar C, Singh P, Koorbanally NA. Synthesis, characterization, anticancer and antibacterial activity of some novel pyrano [2,3-d] pyrimidinone carbonitrile derivatives. Anticancer Agents Med Chem. 2017;17:719–25.

    PubMed  Google Scholar 

  21. Chung PY, Toh YS. Anti-biofilm agents: recent breakthrough against multi-drug resistant Staphylococcus aureus. Pathog Dis. 2014;70:231–9.

    PubMed  Google Scholar 

  22. Perumal S, Mahmud R. Chemical analysis, inhibition of biofilm formation and biofilm eradication potential of Euphorbia hirta L. against clinical isolates and standard strains. BMC Complement Altern Med. 2013;13:346.

    PubMed  PubMed Central  Google Scholar 

  23. Wu CY, Su TY, Wang MY, Yang SF, Mar K, Hung SL. Inhibitory effects of tea catechin epigallocatechin-3-gallate against biofilms formed from Streptococcus mutans and a probiotic lactobacillus strain. Arch Oral Biol. 2018;26:69–77.

    Google Scholar 

  24. Keeling CI, Bohlmann J. Genes, enzymes and chemicals of terpenoid diversity in the constitutive and induced defense of confers against insects and pathogens. New Phytol. 2006;170:657–75.

    PubMed  Google Scholar 

  25. Kitaoka N, Lu X, Yang B, Peters RJ. The application of synthetic biology to elucidation of Plant mono-, sesqui-, and diterpenoid metabolism. Mol Plant. 2015;8:6–16.

    PubMed  Google Scholar 

  26. Kowalski RJ, Giannakakou P, Hamel E. Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol®). J Biol Chem. 1997;272:2534–41.

    PubMed  Google Scholar 

  27. Galeotti N, Di Cesare Mannelli L, Mazzanti G, Bartolini A, Ghelardini C. Menthol: a natural analgesic compound. Neurosci Lett. 2002;322(3):145–8.

    PubMed  Google Scholar 

  28. Horiuchi K, Shiota S, Hatano T, Yoshida T, Kuroda T, Tsuchiya T. Antimicrobial activity of oleanolic acid from Salvia officinalis and related compounds on vancomycin-resistant enterococci (VRE). Biol Pharm Bull. 2007;30:1147–9.

    PubMed  Google Scholar 

  29. Raut JS, Shinde RB, Chauhan NM, Karuppayil SM. Terpenoids of plant origin inhibit morphogenesis, adhesion, and biofilm formation by Candida albicans. Biofouling. 2013;29:87–96.

    PubMed  Google Scholar 

  30. Zeiss HH. The chemistry of the resin acids. Chem Rev. 1948;42:163–87.

    PubMed  Google Scholar 

  31. Fernández MA, Tornos MP, García MD, de Heras B, Villar AM, Sáenz MT. Anti-inflammatory activity of abietic acid, a diterpene isolated from Pimenta recemosa var. grissea. J Pharm Pharmacol. 2001;53:867–72.

    PubMed  Google Scholar 

  32. Kim NH, Son Y, Jeong SO, Hur JM, Bang HS, Lee KN, Kim EC, Chung HT, Pae HO. Tetrahydroabietic acid, a reduced abietic acid, inhibits the production of inflammatory mediators in RAW264.7 macrophages activated with lipopolysaccharide. J Clin Biochem Nutr. 2010;46:119–25.

    PubMed  PubMed Central  Google Scholar 

  33. Ukiya M, Kawaguchi T, Ishii K, Ogihara E, Tachi Y, Kurita M, Ezaki Y, Fukatsu M, Kushi Y, Akihisa T. Cytotoxic activities of amino acid-conjugate derivatives of abietane-type diterpenoids against human cancer cell lines. Chem Biodivers. 2013;10:1260–8.

    PubMed  Google Scholar 

  34. Yoshida N, Takada T, Yamamura Y, Adachi I, Suzuki H, Kawakami J. Inhibitory effects of terpenoids on multidrug resistance-associated protein 2- and breast cancer resistance protein-mediated transport. Drug Metab Dispos. 2008;36:1206–11.

    PubMed  Google Scholar 

  35. Ohtsu H, Tanaka R, In Y, Matsunaga S, Tokuda H, Nishino H. Abietane diterpenoids from the cones of Larix kaempferi and their inhibitory effects on Epstein-Barr virus activation. Planta Med. 2001;67:55–60.

    PubMed  Google Scholar 

  36. Ganewatta MS, Miller KP, Singleton P, Mehrpouya-Bahrami P, Chen YP, Yan Y, Nagarkatti M, Nagarkatti P, Decho AW, Tang C. Antibacterial and biofilm-disrupting coatings from resin acid-derived materials. Biomacromol. 2015;16:3336–44.

    Google Scholar 

  37. Naruishi K, Takashiba S, Nishimura F, Chou HH, Arai H, Yamada H, Murayama Y. Impairment of gingival fibroblast adherence by IL-6/sIL-6R. J Dent Res. 2001;80:1421–4.

    PubMed  Google Scholar 

  38. Matsumi Y, Fujita K, Takashima Y, Yanagida K, Morikawa Y, Matsumoto-Nakano M. Contribution of glucan-binding protein A to firm and stable biofilm formation by Streptococcus mutans. Mol Oral Microbiol. 2015;30:217–26.

    PubMed  Google Scholar 

  39. Song JH, Kim SK, Chang KW, Han SK, Yi HK, Jeon JG. In vitro inhibitory effects of Polygonum cuspidatum on bacterial viability and virulence factors of Streptococcus mutans and Streptococcus sobrinus. Arch Oral Biol. 2006;51(12):1131–40 (Epub).

    PubMed  Google Scholar 

  40. Almagor J, Temkin E, Benenson I, Fallach N, Carmeli Y, DRIVE-AB consortium. The impact of antibiotic use on transmission of resistant bacteria in hospitals: Insights from an agent-based model. PLoS One. 2018;13:e0197111.

    PubMed  PubMed Central  Google Scholar 

  41. World Health Organization (WHO). Antimicrobial resistance: global report on surveillance. Geneva: WHO; 2014.

    Google Scholar 

  42. Krzyściak W, Jurczak A, Kościelniak D, Bystrowska B, Skalniak A. The virulence of Streptococcus mutans and the ability to form biofilms. Eur J Clin Microbiol Infect Dis. 2014;33:499–515.

    PubMed  Google Scholar 

  43. Hamada S, Slade HD. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev. 1980;44(2):331–84.

    PubMed  PubMed Central  Google Scholar 

  44. He J, Li Y, Cao Y, Xue J, Zhou X. The oral microbiome diversity and its relation to human disease. Folia Microbiol. 2015;60:69–80.

    Google Scholar 

  45. Arimatsu K, Yamada H, Miyazawa H, Minagawa T, Nakajima M, Ryder MI, Gotoh K, Motooka D, Nakamura S, Iida T, Yamazaki K. Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep. 2014;6:4828.

    Google Scholar 

  46. Kostic AG, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J, Baselga J, Liu C, Shivdasani RA, Ogino S, Meyarson M. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292–8.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Prof. Teruo Kuroda, Department of Microbiology, School of Pharmaceutical sciences, Hiroshima University, for his support from the beginning of this research. We would like to express our gratitude to Prof. Hiroshi Maeda, Department of Endodontics, Osaka Dental University, for his continuous dedication to this work.

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Authors and Affiliations

  1. Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Yuki Ito, Keisuke Yamashiro, Fumi Mineshiba, Kimito Hirai, Kazuhiro Omori, Tadashi Yamamoto & Shogo Takashiba

  2. Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Takashi Ito

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  1. Yuki Ito
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10266_2019_456_MOESM1_ESM.tiff

Supplementary Fig. 1: Structural formula of abietic acid: Terpenes consist of isoprene units with 5 carbons. Abietic acid is a diterpene derived from four isoprenes (molecular weight: 302.44)

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Ito, Y., Ito, T., Yamashiro, K. et al. Antimicrobial and antibiofilm effects of abietic acid on cariogenic Streptococcus mutans. Odontology 108, 57–65 (2020). https://doi.org/10.1007/s10266-019-00456-0

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