Research Focus

The role of extracellular polysaccharide matrix in the pathogenicity of oral biofilms; Development of effective therapeutics against biofilms

Research Overview

Oral diseases related to dental biofilms continue to afflict the majority of the World's population. Among them, dental caries is the most prevalent and costly oral infectious disease. This ubiquitous disease results from the interaction of specific bacteria and constituents of the diet within biofilms formed on the tooth surface. The majority of biofilm matrices are composed of polysaccharides, which provide bacterial binding sites, physical integrity and stability on the surface and influence the microenvironment of the biofilm. The exact structural and molecular basis of the role of these extracellular polysaccharides (EPS) in the development of cariogenic biofilms is being actively explored.

Our laboratory is focused on three major goals: 1) to understand the sequence of synthesis and assembly of complex polysaccharides (mostly high-molecular-weight polymers of glucose and fructose) in the matrix at molecular and structural levels using genomic, spectroscopic and fluorescence imaging techniques, 2) to elucidate how the structural and biophysical changes in the matrix affect the pathogenicity of the biofilms, and 3) to develop novel anti-biofilm therapies that could disrupt EPS matrix formation. We are particularly interested in finding new naturally occurring anti-biofilm agents from plant-derived foods and organic waste products. We work primarily with mono- and multi-species biofilms; Streptococcus mutans is our model organism because this bacterium is a key contributor for the synthesis of EPS and acid production within biofilms, and generally regarded as the primary microbial culprit of dental caries.

• Gregoire S, Xiao J, Silva BB, Gonzalez I, Agidi PS, Klein MI, Ambatipudi KS, Rosalen PL, Bauserman R, Waugh RE, Koo H. Role of glucosyltransferase B in interactions of Candida albicans with Streptococcus mutans and with an experimental pellicle on hydroxyapatite surfaces. Appl Environ Microbiol. 2011 Sep; 77(18):6357-67.
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• Jeon J, Jeong JH, Baek JH, Koo HJ, Park WH, Yang JS, Yu MH, Kim S, Pak YK. Network clustering revealed the systemic alterations of mitochondrial protein expression. PLoS Comput Biol. 2011 Jun; 7(6):e1002093.
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• Jeon JG, Rosalen PL, Falsetta ML, Koo H. Natural products in caries research: current (limited) knowledge, challenges and future perspective. Caries Res. 2011; 45(3):243-63.
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• Jeon JG, Pandit S, Xiao J, Gregoire S, Falsetta ML, Klein MI, Koo H. Influences of trans-trans farnesol, a membrane-targeting sesquiterpenoid, on Streptococcus mutans physiology and survival within mixed-species oral biofilms. Int J Oral Sci. 2011 Apr; 3(2):98-106.
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• 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.
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• Catalán MA, Scott-Anne K, Klein MI, Koo H, Bowen WH, Melvin JE. Elevated incidence of dental caries in a mouse model of cystic fibrosis. PLoS One. 2011; 6(1):e16549.
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• Klein MI, Xiao J, Heydorn A, Koo H. An analytical tool-box for comprehensive biochemical, structural and transcriptome evaluation of oral biofilms mediated by mutans streptococci. J Vis Exp. 2011; (47).
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• Ambatipudi KS, Hagen FK, Delahunty CM, Han X, Shafi R, Hryhorenko J, Gregoire S, Marquis RE, Melvin JE, Koo H, Yates JR. Human common salivary protein 1 (CSP-1) promotes binding of Streptococcus mutans to experimental salivary pellicle and glucans formed on hydroxyapatite surface. J Proteome Res. 2010 Dec 3; 9(12):6605-14.
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• Klein MI, DeBaz L, Agidi S, Lee H, Xie G, Lin AH, Hamaker BR, Lemos JA, Koo H. Dynamics of Streptococcus mutans transcriptome in response to starch and sucrose during biofilm development. PLoS One. 2010; 5(10):e13478.
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• Murata RM, Branco-de-Almeida LS, Franco EM, Yatsuda R, dos Santos MH, de Alencar SM, Koo H, Rosalen PL. Inhibition of Streptococcus mutans biofilm accumulation and development of dental caries in vivo by 7-epiclusianone and fluoride. Biofouling. 2010 Oct; 26(7):865-72.
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• Branco-de-Almeida LS, Murata RM, Franco EM, dos Santos MH, de Alencar SM, Koo H, Rosalen PL. Effects of 7-epiclusianone on Streptococcus mutans and caries development in rats. Planta Med. 2011 Jan; 77(1):40-5.
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• Koo H, Xiao J, Klein MI, Jeon JG. Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms. J Bacteriol. 2010 Jun; 192(12):3024-32.
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• Koo H, Duarte S, Murata RM, Scott-Anne K, Gregoire S, Watson GE, Singh AP, Vorsa N. 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. 2010; 44(2):116-26.
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• Aires CP, Koo H, Sassaki GL, Iacomini M, Cury JA. A procedure for characterizing glucans synthesized by purified enzymes of cariogenic Streptococcus mutans. Int J Biol Macromol. 2010 Jun; 46(5):551-4.
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• Lemos JA, Abranches J, Koo H, Marquis RE, Burne RA. Protocols to study the physiology of oral biofilms. Methods Mol Biol. 2010; 666:87-102.
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• Koo H, Xiao J, Klein MI. Extracellular polysaccharides matrix--an often forgotten virulence factor in oral biofilm research. Int J Oral Sci. 2009 Dec; 1(4):229-34.
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• Xiao J, Koo H. Structural organization and dynamics of exopolysaccharide matrix and microcolonies formation by Streptococcus mutans in biofilms. J Appl Microbiol. 2010 Jun; 108(6):2103-13.
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• Jeon JG, Klein MI, Xiao J, Gregoire S, Rosalen PL, Koo H. Influences of naturally occurring agents in combination with fluoride on gene expression and structural organization of Streptococcus mutans in biofilms. BMC Microbiol. 2009; 9:228.
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• Kajfasz JK, Martinez AR, Rivera-Ramos I, Abranches J, Koo H, Quivey RG, Lemos JA. Role of Clp proteins in expression of virulence properties of Streptococcus mutans. J Bacteriol. 2009 Apr; 191(7):2060-8.
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• Koo H, Jeon JG. Naturally occurring molecules as alternative therapeutic agents against cariogenic biofilms. Adv Dent Res. 2009; 21(1):63-8.
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• Berkowitz RJ, Koo H, McDermott MP, Whelehan MT, Ragusa P, Kopycka-Kedzierawski DT, Karp JM, Billings R. Adjunctive chemotherapeutic suppression of mutans streptococci in the setting of severe early childhood caries: an exploratory study. J Public Health Dent. 2009; 69(3):163-7.
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• Klein MI, Duarte S, Xiao J, Mitra S, Foster TH, Koo H. Structural and molecular basis of the role of starch and sucrose in Streptococcus mutans biofilm development. Appl Environ Microbiol. 2009 Feb; 75(3):837-41.
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• Paes Leme AF, Bellato CM, Bedi G, Cury AA, Koo H, Cury JA. Effects of sucrose on the extracellular matrix of plaque-like biofilm formed in vivo, studied by proteomic analysis. Caries Res. 2008; 42(6):435-43.
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• Aires CP, Del Bel Cury AA, Tenuta LM, Klein MI, Koo H, Duarte S, Cury JA. Effect of starch and sucrose on dental biofilm formation and on root dentine demineralization. Caries Res. 2008; 42(5):380-6.
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• Lima EM, Koo H, Vacca Smith AM, Rosalen PL, Del Bel Cury AA. Adsorption of salivary and serum proteins, and bacterial adherence on titanium and zirconia ceramic surfaces. Clin Oral Implants Res. 2008 Aug; 19(8):780-5.
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• Cury JA, Seils J, Koo H. Isolation and purification of total RNA from Streptococcus mutans in suspension cultures and biofilms. Braz Oral Res. 2008 Jul-Sep; 22(3):216-22.
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• Koo H. Strategies to enhance the biological effects of fluoride on dental biofilms. Adv Dent Res. 2008; 20(1):17-21.
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• Duarte S, Klein MI, Aires CP, Cury JA, Bowen WH, Koo H. Influences of starch and sucrose on Streptococcus mutans biofilms. Oral Microbiol Immunol. 2008 Jun; 23(3):206-12.
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• Murata RM, Branco de Almeida LS, Yatsuda R, Dos Santos MH, Nagem TJ, Rosalen PL, Koo H. Inhibitory effects of 7-epiclusianone on glucan synthesis, acidogenicity and biofilm formation by Streptococcus mutans. FEMS Microbiol Lett. 2008 May; 282(2):174-81.
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• Almeida LS, Murata RM, Yatsuda R, Dos Santos MH, Nagem TJ, Alencar SM, Koo H, Rosalen PL. Antimicrobial activity of Rheedia brasiliensis and 7-epiclusianone against Streptococcus mutans. Phytomedicine. 2008 Oct; 15(10):886-91.
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• Thimothe J, Bonsi IA, Padilla-Zakour OI, Koo H. Chemical characterization of red wine grape (Vitis vinifera and Vitis interspecific hybrids) and pomace phenolic extracts and their biological activity against Streptococcus mutans. J Agric Food Chem. 2007 Dec 12; 55(25):10200-7.
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• Gregoire S, Singh AP, Vorsa N, Koo H. Influence of cranberry phenolics on glucan synthesis by glucosyltransferases and Streptococcus mutans acidogenicity. J Appl Microbiol. 2007 Nov; 103(5):1960-8.
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• Cury JA, Koo H. Extraction and purification of total RNA from Streptococcus mutans biofilms. Anal Biochem. 2007 Jun 15; 365(2):208-14.
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• Fozo EM, Scott-Anne K, Koo H, Quivey RG. Role of unsaturated fatty acid biosynthesis in virulence of Streptococcus mutans. Infect Immun. 2007 Mar; 75(3):1537-9.
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• Paes Leme AF, Koo H, Bellato CM, Bedi G, Cury JA. The role of sucrose in cariogenic dental biofilm formation--new insight. J Dent Res. 2006 Oct; 85(10):878-87.
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• Duarte S, Gregoire S, Singh AP, Vorsa N, Schaich K, Bowen WH, Koo H. Inhibitory effects of cranberry polyphenols on formation and acidogenicity of Streptococcus mutans biofilms. FEMS Microbiol Lett. 2006 Apr; 257(1):50-6.
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• Koo H, Seils J, Abranches J, Burne RA, Bowen WH, Quivey RG. Influence of apigenin on gtf gene expression in Streptococcus mutans UA159. Antimicrob Agents Chemother. 2006 Feb; 50(2):542-6.
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• Koo H, Nino de Guzman P, Schobel BD, Vacca Smith AV, Bowen WH. Influence of cranberry juice on glucan-mediated processes involved in Streptococcus mutans biofilm development. Caries Res. 2006; 40(1):20-7.
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• Aires CP, Tabchoury CP, Del Bel Cury AA, Koo H, Cury JA. Effect of sucrose concentration on dental biofilm formed in situ and on enamel demineralization. Caries Res. 2006; 40(1):28-32.
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• Koo H, Sheng J, Nguyen PT, Marquis RE. Co-operative inhibition by fluoride and zinc of glucosyl transferase production and polysaccharide synthesis by mutans streptococci in suspension cultures and biofilms. FEMS Microbiol Lett. 2006 Jan; 254(1):134-40.
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• Koo H, Schobel B, Scott-Anne K, Watson G, Bowen WH, Cury JA, Rosalen PL, Park YK. Apigenin and tt-farnesol with fluoride effects on S. mutans biofilms and dental caries. J Dent Res. 2005 Nov; 84(11):1016-20.
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• Hayacibara MF, Koo H, Rosalen PL, Duarte S, Franco EM, Bowen WH, Ikegaki M, Cury JA. In vitro and in vivo effects of isolated fractions of Brazilian propolis on caries development. J Ethnopharmacol. 2005 Oct 3; 101(1-3):110-5.
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• Kho HS, Vacca Smith AM, Koo H, Scott-Anne K, Bowen WH. Interactions of Streptococcus mutans glucosyltransferase B with lysozyme in solution and on the surface of hydroxyapatite. Caries Res. 2005 Sep-Oct; 39(5):411-6.
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• Duarte S, Rosalen PL, Hayacibara MF, Cury JA, Bowen WH, Marquis RE, Rehder VL, Sartoratto A, Ikegaki M, Koo H. The influence of a novel propolis on mutans streptococci biofilms and caries development in rats. Arch Oral Biol. 2006 Jan; 51(1):15-22.
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• Isla MI, Paredes-Guzman JF, Nieva-Moreno MI, Koo H, Park YK. Some chemical composition and biological activity of northern Argentine propolis. J Agric Food Chem. 2005 Feb 23; 53(4):1166-72.
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• Chatfield CH, Koo H, Quivey RG. The putative autolysin regulator LytR in Streptococcus mutans plays a role in cell division and is growth-phase regulated. Microbiology. 2005 Feb; 151(Pt 2):625-31.
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• Yatsuda R, Rosalen PL, Cury JA, Murata RM, Rehder VL, Melo LV, Koo H. Effects of Mikania genus plants on growth and cell adherence of mutans streptococci. J Ethnopharmacol. 2005 Feb 28; 97(2):183-9.
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• Hayacibara MF, Koo H, Vacca-Smith AM, Kopec LK, Scott-Anne K, Cury JA, Bowen WH. The influence of mutanase and dextranase on the production and structure of glucans synthesized by streptococcal glucosyltransferases. Carbohydr Res. 2004 Aug 23; 339(12):2127-37.
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• Koo H, Hayacibara MF, Schobel BD, Cury JA, Rosalen PL, Park YK, Vacca-Smith AM, Bowen WH. Inhibition of Streptococcus mutans biofilm accumulation and polysaccharide production by apigenin and tt-farnesol. J Antimicrob Chemother. 2003 Nov; 52(5):782-9.
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• Duarte S, Koo H, Bowen WH, Hayacibara MF, Cury JA, Ikegaki M, Rosalen PL. Effect of a novel type of propolis and its chemical fractions on glucosyltransferases and on growth and adherence of mutans streptococci. Biol Pharm Bull. 2003 Apr; 26(4):527-31.
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• Hayacibara MF, Rosa OP, Koo H, Torres SA, Costa B, Cury JA. Effects of fluoride and aluminum from ionomeric materials on S. mutans biofilm. J Dent Res. 2003 Apr; 82(4):267-71.
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• Koo H, Pearson SK, Scott-Anne K, Abranches J, Cury JA, Rosalen PL, Park YK, Marquis RE, Bowen WH. Effects of apigenin and tt-farnesol on glucosyltransferase activity, biofilm viability and caries development in rats. Oral Microbiol Immunol. 2002 Dec; 17(6):337-43.
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• Koo H, Cury JA, Rosalen PL, Ambrosano GM, Ikegaki M, Park YK. Effect of a mouthrinse containing selected propolis on 3-day dental plaque accumulation and polysaccharide formation. Caries Res. 2002 Nov-Dec; 36(6):445-8.
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• Koo H, Rosalen PL, Cury JA, Park YK, Bowen WH. Effects of compounds found in propolis on Streptococcus mutans growth and on glucosyltransferase activity. Antimicrob Agents Chemother. 2002 May; 46(5):1302-9.
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• Koo H, Rosalen PL, Cury JA, Ambrosano GM, Murata RM, Yatsuda R, Ikegaki M, Alencar SM, Park YK. Effect of a new variety of Apis mellifera propolis on mutans Streptococci. Curr Microbiol. 2000 Sep; 41(3):192-6.
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• Koo H, Vacca Smith AM, Bowen WH, Rosalen PL, Cury JA, Park YK. Effects of Apis mellifera propolis on the activities of streptococcal glucosyltransferases in solution and adsorbed onto saliva-coated hydroxyapatite. Caries Res. 2000 Sep-Oct; 34(5):418-26.
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• Koo H, Gomes BP, Rosalen PL, Ambrosano GM, Park YK, Cury JA. In vitro antimicrobial activity of propolis and Arnica montana against oral pathogens. Arch Oral Biol. 2000 Feb; 45(2):141-8.
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• Cury JA, Rocha EP, Koo H, Francisco SB, Del Bel Cury AA. Effect of saccharin on antibacterial activity of chlorhexidine gel. Braz Dent J. 2000; 11(1):29-34.
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• Koo H, Rosalen PL, Cury JA, Park YK, Ikegaki M, Sattler A. Effect of Apis mellifera propolis from two Brazilian regions on caries development in desalivated rats. Caries Res. 1999 Sep-Oct; 33(5):393-400.
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• Koo RH, Cury JA. Soluble calcium/SMFP dentifrice: effect on enamel fluoride uptake and remineralization. Am J Dent. 1998 Aug; 11(4):173-6.
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• Park YK, Koo MH, Abreu JA, Ikegaki M, Cury JA, Rosalen PL. Antimicrobial activity of propolis on oral microorganisms. Curr Microbiol. 1998 Jan; 36(1):24-8.
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• Park YK, Koo MH, Oliveira IM. Biochemical characteristics of osmophilic yeasts isolated from pollens and honey. Biosci Biotechnol Biochem. 1996 Nov; 60(11):1872-3.
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