Abstract
Streptococcus mutans is a common pathogen present in the oral cavity and it causes dental caries for all aged groups of people, in particular, children. S. mutans have several virulence factors such as acidogenecity, aciduricity, adhesion and biofilm formation. These virulence factors are working together and lead to the development of caries in the tooth surface. The present study aimed to investigate the anticariogenic potential of 3, 5-di-tert-butylphenol (3, 5-DTBP) against S. mutans. 3, 5-DTBP biofilm inhibitory concentration (BIC) was found at 100 µg/ml concentration without any lethal effect on the growth. Moreover, 3, 5-DTBP significantly reduced water soluble and water insoluble glucans production, in concurrence with downregulation of gtfBC genes. Moreover, acidogenicity associated virulence factors such as lactate dehydrogenase and enolase enzymatic production was arrested upon 3, 5-DTBP treatment. In addition, 3, 5-DTBP greatly reduced acidtolerance ability through impedes of F1F0-ATPase. Gene expression analysis unveiled the downregulation of gtfB, gtfC, gtfD, vicRK, comDE, gbpB, smu0630 and relA upon 3, 5-DTBP treatment. The present study paves the way for exhibiting 3, 5-DTBP as a promising therapeutic agent to control S. mutans infections.
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References
Bagis B, Baltacioglu E, Oezcan M, Ustaomer S (2011) Evaluation of chlorhexidine gluconate mouthrinse-induced staining using a digital colorimeter: an in vivo study. Quintessence Int 42:213–223
Ban SH, Kim JE, Pandit S, Jeon JG (2012) Influences of Dryopteris crassirhizoma extract on the viability, growth and virulence properties of Streptococcus mutans. Molecules 17:9231–9244
Banas JA (2013) Delaying Streptococcus mutans colonization in children leads to reduced caries experience. J Evid Based Dent Pract 13:67–69
Belli WA, Buckley DH, Marquis RE (1995) Weak acid effects and fluoride inhibition of glycolysis by Streptococcus mutans GS-5. Can J Microbiol 41:785–791
Bencini DA, Shanley MS, Wild JR, O’Donovan GA (1983) New assay for enzymatic phosphate release: application to aspartate transcarbamylase and other enzymes. Anal Biochem 132:259–264
Borshchevskaya LN, Gordeeva TL, Kalinina AN, Sineokii SP (2016) Spectrophotometric determination of lactic acid. J Anal Chem 71:755–758
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analy Biochem 72:248–254
Brown TA Jr, Ahn SJ, Frank RN, Chen YYM, Lemos JA, Burne RA (2005) A hypothetical protein of Streptococcus mutans is critical for biofilm formation. Infect Immun 73:3147–3151
Cardoso JG, Iorio NL, Rodrigues LF, Couri ML, Farah A, Maia LC, Antonio AG (2016) Influence of a Brazilian wild green propolis on the enamel mineral loss and Streptococcus mutans’ count in dental biofilm. Arch Oral Biol 65:77–81
Crow VL, Pritchard GG (1977) Fructose 1, 6-diphosphate-activated L-lactate dehydrogenase from Streptococcus lactis: kinetic properties and factors affecting activation. J Bacteriol 131:82–91
Deng DM, Liu MJ, Ten Cate JM, Crielaard W (2007) The VicRK system of Streptococcus mutans responds to oxidative stress. J Dent Res 86:606–610
Flemming HC, Wingender J (2010) The biofilm matrix. Nat Rev Microbiol 8:623–633
Gabe V, Kacergius T, Abu-Lafi S, Zeidan M, Abu-Farich B, Austys D, Masalha M, Rayan A (2019) Suppressive effects of octyl gallate on Streptococcus mutans biofilm formation, acidogenicity, and gene expression. Molecules 24:3170
Gabe V, Zeidan M, Kacergius T, Bratchikov M, Falah M, Rayan A (2020) Lauryl gallate activity and Streptococcus mutans: its effects on biofilm formation, acidogenicity and gene expression. Molecules 25:3685
Gowrishankar S, Poornima B, Pandian SK (2014) Inhibitory efficacy of cyclo (l-leucyl-l-prolyl) from mangrove rhizosphere bacterium–Bacillus amyloliquefaciens (MMS-50) toward cariogenic properties of Streptococcus mutans. Res Microbiol 165:278–289
Gyawali R, Ibrahim SA (2014) Natural products as antimicrobial agents. Food Control 46:412–429
Hamilton IR, Buckley ND (1991) Adaptation by Streptococcus mutans to acid tolerance. Oral Microbiol Immunol 6:65–71
Hasan S, Singh K, Danisuddin M, Verma PK, Khan AU (2014a) Inhibition of major virulence pathways of Streptococcus mutans by quercitrin and deoxynojirimycin: a synergistic approach of infection control. PLoS One 9:e91736
Hasan S, Singh K, Danisuddin M, Verma PK, Khan AU (2014b) Inhibition of major virulence pathways of Streptococcus mutans by quercitrin and deoxynojirimycin: a synergistic approach of infection control. PLoS One 9:91736
Karuppiah V, Thirunanasambandham R, Thangaraj G (2021) Anti-quorum sensing and antibiofilm potential of 1, 8-cineole derived from Musa paradisiaca against Pseudomonas aeruginosa strain PAO1. World J Microbiol Biotechnol 37:1–12
Khan R, Zakir M, Khanam Z, Shakil S, Khan AU (2010) Novel compound from Trachyspermum ammi (ajowan caraway) seeds with antibiofilm and anti-adherence activities against Streptococcus mutans: a potential chemotherapeutic agent against dental caries. J Appl Microbiol 109(6):2151–2159
Khan R, Adil M, Danishuddin M, Verma PK, Khan AU (2012) In vitro and in vivo inhibition of Streptococcus mutans biofilm by Trachyspermum ammi seeds: an approach of alternative medicine. Phytomedicine 19:747–755
Koo H, Xiao J, Klein MI, Jeon JG (2010) Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms. J Bacteriol 192:3024–3032
Korithoski B, Lévesque CM, Cvitkovitch DG (2007) Involvement of the detoxifying enzyme lactoylglutathione lyase in Streptococcus mutans aciduricity. J Bacteriol 189:7586–7592
Lemos JA, Burne RA (2008) A model of efficiency: stress tolerance by Streptococcus mutans. Microbiology 154:3247
Li YH, Tang N, Aspiras MB, Lau PC, Lee JH, Ellen RP, Cvitkovitch DG (2002) A quorum-sensing signaling system essential for genetic competence in Streptococcus mutans is involved in biofilm formation. J Bacteriol 184:2699–2708
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
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2–∆∆CT method. Methods 25:402–408
Marsh PD (2004) Dental plaque as a microbial biofilm. Caries Res 38:204–211
Martins ML, de França Leite KL, Pacheco-Filho EF, de Miranda Pereira AF, Romanos MTV, Maia LC, Fonseca-Gonçalves A, Padilha WWN, Cavalcanti YW (2018) Efficacy of red propolis hydro-alcoholic extract in controlling Streptococcus mutans biofilm build-up and dental enamel demineralization. Archiv Oral Biol 93:56–65
Matsui R, Cvitkovitch D (2010) Acid tolerance mechanisms utilized by Streptococcus mutans. Future Microbiol 5:403–417
Matsumoto M, Minami T, Sasaki H, Sobue S, Hamada S, Ooshima T (1999) Inhibitory effects of oolong tea extract on caries–inducing properties of mutans streptococci. Caries Res 33:441–445
Mattos-Graner RO, Duncan MJ (2017) Two-component signal transduction systems in oral bacteria. J Oral Microbiol 9:1400858
Oh ET, So JS (2003) A rapid method for RNA preparation from Gram-positive bacteria. J Microbiol Methods 52:395–398
Postma PW, Lengeler JW, Jacobson GR (1993) Phosphoenolpyruvate: carbohydrate phosphotransferase systems of bacteria. Microbiol Mol Biol Rev 57:543–594
Rathna J, Bakkiyaraj D, Pandian SK (2016) Anti-biofilm mechanisms of 3,5-di-tert-butylphenol against clinically relevant fungal pathogens. Biofouling 32:979–993
Ren Z, Cui T, Zeng J, Chen L, Zhang W, Xu X, Cheng L, Li M, Li J, Zhou X, Li Y (2016) Molecule targeting glucosyltransferase inhibits Streptococcus mutans biofilm formation and virulence. Antimicrob Agents Chemother 60:126–135
Senadheera D, Cvitkovitch DG (2008) Quorum sensing and biofilm formation by Streptococcus mutans. In: Bacterial signal transduction: networks and drug targets. Springer, New York, pp 178–188
Senadheera MD, Guggenheim B, Spatafora GA, Huang YC, Choi J, Hung DC, Treglown JS, Goodman SD, Ellen RP, Cvitkovitch DG (2005) A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development. J Bacteriol 187:4064–4076
Smith EG, Spatafora GA (2012) Gene regulation in S. mutans: complex control in a complex environment. J Dent Res 91:133–141
Subramenium GA, Vijayakumar K, Pandian SK (2015) Limonene inhibits streptococcal biofilm formation by targeting surface-associated virulence factors. J Med Microbiol 64:879–890
Sorroche FG, Spesia MB, Zorreguieta Á, Giordano W (2012) A positive correlation between bacterial autoaggregation and biofilm formation in native Sinorhizobium meliloti isolates from Argentina. Appl Environ Microbiol 78:4092–4101
Tremblay YD, Lo H, Li YH, Halperin SA, Lee SF (2009) Expression of the Streptococcus mutans essential two-component regulatory system VicRK is pH and growth-phase dependent and controlled by the LiaFSR three-component regulatory system. Microbiology 155:2856–2865
Van Sorge NM, Beasley FC, Gusarov I, Gonzalez DJ, von Köckritz-Blickwede M, Anik S, Borkowski AW, Dorrestein PC, Nudler E, Nizet V (2013) Methicillin-resistant Staphylococcus aureus bacterial nitric-oxide synthase affects antibiotic sensitivity and skin abscess development. J Biol Chem 288:6417–6426
Vijayakumar K, Ramanathan T (2018) Antiquorum sensing and biofilm potential of 5-hydroxymethylfurfural against Gram positive pathogens. Microb Pathog 125:48–50
Vijayakumar K, Ramanathan T (2020) Musa acuminata and its bioactive metabolite 5-Hydroxymethylfurfural mitigates quorum sensing (las and rhl) mediated biofilm and virulence production of nosocomial pathogen Pseudomonas aeruginosa in vitro. J Ethnopharmacol 246:112242
Vijayakumar K, Bharathidasan V, Manigandan V, Jeyapragash D (2020) Quebrachitol inhibits biofilm formation and virulence production against methicillin-resistant Staphylococcus aureus. Microb Pathog 149:104286
Viszwapriya D, Subramenium GA, Radhika S, Pandian SK (2017) Betulin inhibits cariogenic properties of Streptococcus mutans by targeting vicRK and gtf genes. Antonie Van Leeuwenhoek 110:153–165
Welin-Neilands J, Svensater G (2007) Acid tolerance of biofilm cells of Streptococcus mutans. Appl Environ Microbiol 73:5633–5638
Xiao J, Klein MI, Falsetta ML, Lu B, Delahunty CM, Yates JR III, Heydorn A, Koo H (2012) The exopolysaccharide matrix modulates the interaction between 3D architecture and virulence of a mixed-species oral biofilm. PLoS Pathog 8:e1002623
Xu X, Zhou XD, Wu CD (2011) The tea catechin epigallocatechin gallate suppresses cariogenic virulence factors of Streptococcus mutans. Antimicrob Agents Chemother 55:1229–1236
Yamashita Y, Tomihisa K, Nakano Y, Shimazaki Y, Oho T, Koga T (1999) Recombination between gtfB and gtfC is required for survival of a dTDP-rhamnose synthesis-deficient mutant of Streptococcus mutans in the presence of sucrose. Infect Immun 67:3693–3697
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
Zhang Z, Liu Y, Lu M, Lyu X, Gong T, Tang B, Wang L, Zeng J, Li Y (2020) Rhodiola rosea extract inhibits the biofilm formation and the expression of virulence genes of cariogenic oral pathogen Streptococcus mutans. Arch Oral Biol 19:104762
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The authors gratefully thank Dr. G. Ashwinkumar Subramenium for support in discussing and fulfilling the work. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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KV Conceptualization of whole work, performed the experiments, data analyzed and co-wrote the manuscript. SM Co-wrote the manuscript,performed the experiments and data analyzed.
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Vijayakumar, K., MuhilVannan, S. 3, 5-Di-tert-butylphenol combat against Streptococcus mutans by impeding acidogenicity, acidurance and biofilm formation. World J Microbiol Biotechnol 37, 202 (2021). https://doi.org/10.1007/s11274-021-03165-5
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DOI: https://doi.org/10.1007/s11274-021-03165-5