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Inhibition of Streptococcus mutans biofilm formation, extracellular polysaccharide production, and virulence by an oxazole derivative

  • Applied microbial and cell physiology
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Abstract

Dental caries, a biofilm-related oral disease, is a result of disruption of the microbial ecological balance in the oral environment. Streptococcus mutans, which is one of the primary cariogenic bacteria, produces glucosyltransferases (Gtfs) that synthesize extracellular polysaccharides (EPSs). The EPSs, especially water-insoluble glucans, contribute to the formation of dental plaque, biofilm stability, and structural integrity, by allowing bacteria to adhere to tooth surfaces and supplying the bacteria with protection against noxious stimuli and other environmental attacks. The identification of novel alternatives that selectively inhibit cariogenic organisms without suppressing oral microbial residents is required. The goal of the current study is to investigate the influence of an oxazole derivative on S. mutans biofilm formation and the development of dental caries in rats, given that oxazole and its derivatives often exhibit extensive and pharmacologically important biological activities. Our data shows that one particular oxazole derivative, named 5H6, inhibited the formation of S. mutans biofilms and prevented synthesis of extracellular polysaccharides by antagonizing Gtfs in vitro, without affecting the growth of the bacteria. In addition, topical applications with the inhibitor resulted in diminished incidence and severity of both smooth and sulcal surface caries in vivo with a lower percentage of S. mutans in the animals’ dental plaque compared to the control group (P < 0.05). Our results showed that this oxazole derivative has the capacity to inhibit biofilm formation and cariogenicity of S. mutans.

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References

  • Ahn SJ, Browngardt CM, Burne RA (2009) Changes in biochemical and phenotypic properties of Streptococcus mutans during growth with aeration. Appl Environ Microbiol 75:2517–2527

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Anderson M (2002) Risk assessment and epidemiology of dental caries: review of the literature. Pediatr Dent 24:377–385

    PubMed  Google Scholar 

  • Barbachyn MR, Ford CW (2003) Oxazolidinone structure-activity relationships leading to linezolid. Angew Chem Int Ed Engl 42:2010–2023

    Article  PubMed  CAS  Google Scholar 

  • Bowen WH (2002) Do we need to be concerned about dental caries in the coming millennium? Crit Rev Oral Biol Med 13:126–131

    Article  PubMed  Google Scholar 

  • Bowen WH, Madison KM, Pearson SK (1988) Influence of desalivation in rats on incidence of caries in intact cagemates. J Dent Res 67:1316–1318

    Article  PubMed  CAS  Google Scholar 

  • Coenye T, Honraet K, Rigole P, Nadal Jimenez P, Nelis HJ (2007) In vitro inhibition of Streptococcus mutans biofilm formation on hydroxyapatite by subinhibitory concentrations of anthraquinones. Antimicrob Agents Chemother 51:1541–1544

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322

    Article  PubMed  CAS  Google Scholar 

  • Cummins D (2013) Dental caries: a disease which remains a public health concern in the 21st century--the exploration of a breakthrough technology for caries prevention. J Clin Dent A:A1–A14

    Google Scholar 

  • Davies D (2003) Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov 2:114–122

    Article  PubMed  CAS  Google Scholar 

  • Davyt D, Serra G (2010) Thiazole and oxazole alkaloids: isolation and synthesis. Mar Drugs 8:2755–2780

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Eguchi Y, Kubo N, Matsunaga H, Igarashi M, Utsumi R (2011) Development of an antivirulence drug against Streptococcus mutans: repression of biofilm formation, acid tolerance, and competence by a histidine kinase inhibitor, walkmycin C. Antimicrob Agents Chemother 55:1475–1484

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fejerskov O (2004) Changing paradigms in concepts on dental caries: consequences for oral health care. Caries Res 38:182–191

    Article  PubMed  CAS  Google Scholar 

  • Hall-Stoodley L, Costerton JW, Stoodley P (2004) Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2:95–108

    Article  PubMed  CAS  Google Scholar 

  • Hamada S, Slade HD (1980) Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev 44:331–384

    PubMed  PubMed Central  CAS  Google Scholar 

  • Hanada N, Kuramitsu HK (1988) Isolation and characterization of the Streptococcus mutans gtfC gene, coding for synthesis of both soluble and insoluble glucans. Infect Immun 56:1999–2005

    PubMed  PubMed Central  CAS  Google Scholar 

  • Hanada N, Kuramitsu HK (1989) Isolation and characterization of the Streptococcus mutans gtfD gene, coding for primer-dependent soluble glucan synthesis. Infect Immun 57:2079–2085

    PubMed  PubMed Central  CAS  Google Scholar 

  • Hirasawa M, Takada K, Otake S (2006) Inhibition of acid production in dental plaque bacteria by green tea catechins. Caries Res 40:265–270

    Article  PubMed  CAS  Google Scholar 

  • Ishihara J, Hatakeyama S (2014) Total synthesis of oxazolomycins. Chem Rec 14:663–677

    Article  PubMed  CAS  Google Scholar 

  • Jin Z (2011) Muscarine, imidazole, oxazole, and thiazole alkaloids. Nat Prod Rep 28:1143–1191

    Article  PubMed  CAS  Google Scholar 

  • Koo H, Hayacibara MF, Schobel BD, Cury JA, Rosalen PL, Park YK, Vacca-Smith AM, Bowen WH (2003) Inhibition of Streptococcus mutans biofilm accumulation and polysaccharide production by apigenin and tt-farnesol. J Antimicrob Chemother 52:782–789

    Article  PubMed  CAS  Google Scholar 

  • Koo H, Duarte S, Murata RM, Scott-Anne K, Gregoire S, Watson GE, Singh AP, Vorsa N (2010) Influence of cranberry proanthocyanidins on formation of biofilms by Streptococcus mutans on saliva-coated apatitic surface and on dental caries development in vivo. Caries Res 44:116–126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kopec LK, Vacca-Smith AM, Bowen WH (1997) Structural aspects of glucans formed in solution and on the surface of hydroxyapatite. Glycobiology 7:929–934

    Article  PubMed  CAS  Google Scholar 

  • Larson RM (1981) Merits and modifications of scoring rat dental caries by Keyes’ method. Animal Models Cariol pp 195–203

  • Lee CG, Park JK (2015) Comparison of inhibitory activity of bioactive molecules on the dextransucrase from Streptococcus mutans. Appl Microbiol Biotechnol. doi:10.1007/s00253-015-6693-z

    Google Scholar 

  • Lemos JA, Burne RA (2008) A model of efficiency: stress tolerance by Streptococcus mutans. Microbiology 154:3247–3255

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li YF, Sun HW, Gao R, Liu KY, Zhang HQ, Fu QH, Qing SL, Guo G, Zou QM (2015) Inhibited biofilm formation and improved antibacterial activity of a novel nanoemulsion against cariogenic Streptococcus mutans in vitro and in vivo. Int J Nanomedicine 10:447–462

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu C, Worthington RJ, Melander C, Wu H (2011) A new small molecule specifically inhibits the cariogenic bacterium Streptococcus mutans in multispecies biofilms. Antimicrob Agents Chemother 55:2679–2687

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu Y, Zhang X, Wang Y, Chen F, Yu Z, Wang L, Chen S, Guo M (2013) Effect of citrus lemon oil on growth and adherence of Streptococcus mutans. World J Microbiol Biotechnol 29:1161–1167

    Article  PubMed  CAS  Google Scholar 

  • Lynch DJ, Fountain TL, Mazurkiewicz JE, Banas JA (2007) Glucan-binding proteins are essential for shaping Streptococcus mutans biofilm architecture. FEMS Microbiol Lett 268:158–165

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ma R, Liu J, Jiang YT, Liu Z, Tang ZS, Ye DX, Zeng J, Huang ZW (2010) Modeling of diffusion transport through oral biofilms with the inverse problem method. Int J Oral Sci 2:190–197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Marsh PD (2003) Are dental diseases examples of ecological catastrophes? Microbiology 149:279–294

    Article  PubMed  CAS  Google Scholar 

  • Mattos-Graner RO, Napimoga MH, Fukushima K, Duncan MJ, Smith DJ (2004) Comparative analysis of Gtf isozyme production and diversity in isolates of Streptococcus mutans with different biofilm growth phenotypes. J Clin Microbiol 42:4586–4592

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murata RM, Branco-de-Almeida LS, Franco EM, Yatsuda R, dos Santos MH, de Alencar SM, Koo H, Rosalen PL (2010) Inhibition of Streptococcus mutans biofilm accumulation and development of dental caries in vivo by 7-epiclusianone and fluoride. Biofouling 26:865–872

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Paes Leme AF, Koo H, Bellato CM, Bedi G, Cury JA (2006) The role of sucrose in cariogenic dental biofilm formation—new insight. J Dent Res 85:878–887

    Article  PubMed  CAS  Google Scholar 

  • Paterson GK, Mitchell TJ (2004) The biology of Gram-positive sortase enzymes. Trends Microbiol 12:89–95

    Article  PubMed  CAS  Google Scholar 

  • Schilling KM, Bowen WH (1992) Glucans synthesized in situ in experimental salivary pellicle function as specific binding sites for Streptococcus mutans. Infect Immun 60:284–295

    PubMed  PubMed Central  CAS  Google Scholar 

  • Selwitz RH, Ismail AI, Pitts NB (2007) Dental caries. Lancet 369:51–59

    Article  PubMed  CAS  Google Scholar 

  • Shang D, Liang H, Wei S, Yan X, Yang Q, Sun Y (2014) Effects of antimicrobial peptide L-K6, a temporin-1CEb analog on oral pathogen growth, Streptococcus mutans biofilm formation, and anti-inflammatory activity. Appl Microbiol Biotechnol 98:8685–8695

    Article  PubMed  CAS  Google Scholar 

  • Sharma S, Lavender S, Woo J, Guo L, Shi W, Kilpatrick-Liverman L, Gimzewski JK (2014) Nanoscale characterization of effect of L-arginine on Streptococcus mutans biofilm adhesion by atomic force microscopy. Microbiology 160:1466–1473

    Article  PubMed  CAS  Google Scholar 

  • Stepanovic S, Vukovic D, Dakic I, Savic B, Svabic-Vlahovic M (2000) A modified microtiter-plate test for quantification of staphylococcal biofilm formation. J Microbiol Methods 40:175–179

    Article  PubMed  CAS  Google Scholar 

  • Stewart PS, Franklin MJ (2008) Physiological heterogeneity in biofilms. Nat Rev Microbiol 6:199–210

    Article  PubMed  CAS  Google Scholar 

  • Terao Y, Isoda R, Murakami J, Hamada S, Kawabata S (2009) Molecular and biological characterization of gtf regulation-associated genes in Streptococcus mutans. Oral Microbiol Immunol 24:211–217

    Article  PubMed  CAS  Google Scholar 

  • Utsumi R (2008) Bacterial signal transduction: networks and drug targets. Preface Adv Exp Med Biol 631:v

  • Wang RK, He XS, Hu W, Lux R, Li JY, Zhou XD, Shi WY (2011) Analysis of interspecies adherence of oral bacteria using a membrane binding assay coupled with polymerase chain reaction-denaturing gradient gel electrophoresis profiling. Int J Oral Sci 3:90–97

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu J, Panek JS (2010) Total synthesis of (−)-virginiamycin M2. Angew Chem Int Ed Engl 49:6165–6168

    Article  PubMed  CAS  Google Scholar 

  • Xie Q, Li J, Zhou X (2008) Anticaries effect of compounds extracted from Galla Ghinensis in a multispecies biofilm model. Oral Microbiol Immunol 23:459–465

    Article  PubMed  CAS  Google Scholar 

  • Yano A, Kikuchi S, Yamashita Y, Sakamoto Y, Nakagawa Y, Yoshida Y (2010) The inhibitory effects of mushroom extracts on sucrose-dependent oral biofilm formation. Appl Microbiol Biotechnol 86:615–623

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to give our thanks to Sang-Joon Ahn (of the laboratory of Robert A. Burne at University of Florida, Gainesville, FL) for providing the gtf mutant strains. This work was supported by the National Natural Science Foundation of China (31200985, 31400040 and 81470035), and State Key Laboratory of Oral Diseases (SKLOD201414).

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Correspondence to Jing Zou or Yuqing Li.

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Animal experiments in this study were approved by West China School of Stomatology Ethics Committee (WCCSSIRB-D-2014-013; Sichuan University, Chengdu, China).

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The authors declare that they have no conflict of interest.

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Lulu Chen and Zhi Ren contributed equally to this work.

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Chen, L., Ren, Z., Zhou, X. et al. Inhibition of Streptococcus mutans biofilm formation, extracellular polysaccharide production, and virulence by an oxazole derivative. Appl Microbiol Biotechnol 100, 857–867 (2016). https://doi.org/10.1007/s00253-015-7092-1

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