Inhibition of Streptococcus mutans polysaccharide synthesis by molecules targeting glycosyltransferase activity

Figures & data

Table 1 Molecules that inhibit glycosyltransferase activity

Category	Source of natural product	Representative substances	Inhibited Gtfs reported	Evidence of cariostatic efficacy in vivo	Reference
Inhibitors derived from natural products
Catechin-based polyphenols	Camellia sinensis (black, green and oolong tea)	Theaflavin (-)-Epigallocatechin gallate (-)-Epicatechin gallate	GtfB (solution) GtfB (solution) GtfB (solution)	Yes (as crude tea extract) Yes (as crude tea extract) Yes (as crude tea extract)	(26–(31))
Flavonoids	Apis mellifera propolis (bee hive)	Apigenin	GtfB, GtfC, and GtfD (solution/surface)	Yes	(36, (37))
		Kaempferol	GtfB, GtfC, and GtfD (solution/surface)	No	(36)
	Vaccinium macrocarpon (cranberry)	Myricetin	GtfB (surface)	No	(42)
Proanthocyanidin oligomers	Cranberry	A-type proanthocyanidin oligomers	GtfB (surface)	Yes	(42, (43))
	Apple	Condensed tannins	Crude Gtfs (solution)	No	(44)
Polymeric polyphenols	Oolong tea	OTF6	GtfB and GtfD (solution)	Yes (as crude tea extract)	(26, (48))
	Cocoa bean hust	Polymeric epicatechins	GtfB, GtfC, and GtfD (solution)	No	(49, (50))
Others	Rheedia gardneriana	7-Epiclusianone	GtfB and GtfC (solution)	No	(51)
	Azadirachta indica (Neem) Melaphis chinensis (Chinese Nutgall)	Gallotannin Gallotannin	Crude Gtfs (solution) Crude Gtfs (solution)	No No	(52) (53)
Synthesized inhibitors
		Quaternary ammonium	Crude Gtfs (solution)	No	(54)
		Aliphatic amines	Crude Gtfs (solution)	No	(54)
		1-Deoxynojirimycin	GtfB, GtfC, and GtfD (solution/surface)	No	(24, (57))
		Tris(hydroxymethyl) aminomethane	Crude Gtfs (solution/surface)	No	(56)
		Trichloro-galactosucrose	GtfB, GtfC, and GtfD (solution/surface)	No	(24)
		Acarbose	GtfB, GtfD (solution)	No	(57)
		Maltose	GtfB (solution)	No	(57)
		Nojirimycin	GtfB (solution)	No	(57)
		Quinoxaline derivative	GtfC and GtfD (solution)	Yes	(58)
Metal ions and oxidizing agents		Zn^2+	GtfB, GtfC, and GtfD (solution)	No	(24)
		Cu^2+	GtfB, GtfC, and GtfD (solution/surface)	No	(24)
		Fe^2+	GtfB, GtfC, and GtfD (solution/surface)	No	(24)
		Fe^3+	GtfB, GtfC, and GtfD (solution/surface)	No	(24)
		Rose bengal	GtfB, GtfC, and GtfD (solution/surface)	No	(24)
		Hypochlorite	GtfB, GtfC, and GtfD (solution/surface)	No	(24)
Antibodies		Antibody to GtfB	GtfB and GtfC (solution/surface)	Yes	(66, (68, 69))
		Antibody to GtfC	GtfB and GtfC (solution/surface)	No	(66)
		Antibody to GtfD	GtfD (solution), GtfC (surface)	No	(66)

Ooshima T, Minami T, Aono W, Izumitani A, Sobue S, Fujiwara T, etal. Oolong tea polyphenols inhibit experimental dental caries in SPF rats infected with mutans streptococci. Caries Res. 1993; 27: 124–9. [PubMed Abstract].

 Google Scholar

Nakahara K, Kawabata S, Ono H, Ogura K, Tanaka T, Ooshima T, etal. Inhibitory effect of oolong tea polyphenols on glycosyltransferases of mutans Streptococci. Appl Environ Microbiol. 1993; 59: 968–73. [PubMed Abstract] [PubMed CentralFull Text].

 Google Scholar

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; 46: 1302–9. [PubMed Abstract] [PubMed CentralFull Text].

 Google Scholar

Koo H, Pearson SK, Scott-Anne K, Abranches J, Cury JA, Rosalen PL, etal. Effects of apigenin and tt-farnesol on glucosyltransferase activity, biofilm viability and caries development in rats. Oral Microbiol Immunol. 2002; 17: 337–43. [PubMed Abstract].

 Google Scholar

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; 103: 1960–8. [PubMed Abstract].

 Google Scholar

Koo H, Duarte S, Murata RM, Scott-Anne K, Gregoire S, Watson GE, etal. 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: 116–26. [PubMed Abstract] [PubMed CentralFull Text].

 Google Scholar

Yanagida A, Kanda T, Tanabe M, Matsudaira F, Oliveira Cordeiro JG. Inhibitory effects of apple polyphenols and related compounds on cariogenic factors of mutans streptococci. J Agric Food Chem. 2000; 48: 5666–71. [PubMed Abstract].

 Google Scholar

Matsumoto M, Hamada S, Ooshima T. Molecular analysis of the inhibitory effects of oolong tea polyphenols on glucan-binding domain of recombinant glucosyltransferases from Streptococcus mutans MT8148. FEMS Microbiol Lett. 2003; 228: 73–80. [PubMed Abstract].

 Google Scholar

Osawa K, Miyazaki K, Shimura S, Okuda J, Matsumoto M, Ooshima T. Identification of cariostatic substances in the cacao bean husk: their anti-glucosyltransferase and antibacterial activities. J Dent Res. 2001; 80: 2000–4. [PubMed Abstract].

 Google Scholar

Hamada S, Kontani M, Hosono H, Ono H, Tanaka T, Ooshima T, etal. Peroxidase-catalyzed generation of catechin oligomers that inhibit glucosyltransferase from Streptococcus sobrinus. FEMS Microbiol Lett. 1996; 143: 35–40. [PubMed Abstract].

 Google Scholar

Murata RM, Branco de Almeida LS, Yatsuda R, Dos Santos MH, Nagem TJ, Rosalen PL, etal. Inhibitory effects of 7-epiclusianone on glucan synthesis, acidogenicity and biofilm formation by Streptococcus mutans. FEMS Microbiol Lett. 2008; 282: 174–81. [PubMed Abstract] [PubMed CentralFull Text].

 Google Scholar

Wolinsky LE, Mania S, Nachnani S, Ling S. The inhibiting effect of aqueous Azadirachta indica (Neem) extract upon bacterial properties influencing in vitro plaque formation. J Dent Res. 1996; 75: 816–22. [PubMed Abstract].

 Google Scholar

Wu-Yuan CD, Chen CY, Wu RT. Gallotannins inhibit growth, water-insoluble glucan synthesis, and aggregation of mutans streptococci. J Dent Res. 1988; 67: 51–5. [PubMed Abstract].

 Google Scholar

Ciardi JE, Bowen WH, Rolla G. The effect of antibacterial compounds on glucosyltransferase activity from Streptococcus mutans. Arch Oral Biol. 1978; 23: 301–5. [PubMed Abstract].

 Google Scholar

Wunder D, Bowen WH. Action of agents on glucosyltransferases from Streptococcus mutans in solution and adsorbed to experimental pellicle. Arch Oral Biol. 1999; 44: 203–14. [PubMed Abstract].

 Google Scholar

Newbrun E, Hoover CI, Walker GJ. Inhibition by acarbose, nojirimycin and 1-deoxynojirimycin of glucosyltransferase produced by oral streptococci. Arch Oral Biol. 1983; 28: 531–6. [PubMed Abstract].

 Google Scholar

Wright WG, Thelwell C, Svensson B, Russell RR. Inhibition of catalytic and glucan-binding activities of a streptococcal GTF forming insoluble glucans. Caries Res. 2002; 36: 353–9. [PubMed Abstract].

 Google Scholar

Ren Z, Cui T, Zeng J, Chen L, Zhang W, Xu X, etal. Molecule targeting Glucosyltransferase Inhibits Streptococcus mutans biofilm formation and virulence. Antimicrob Agents Chemother. 2015; 60: 126–35. [PubMed Abstract].

 Google Scholar

Wunder D, Bowen WH. Effects of antibodies to glucosyltransferase on soluble and insolubilized enzymes. Oral Dis. 2000; 6: 289–96. [PubMed Abstract].

 Google Scholar

Hamada S, Horikoshi T, Minami T, Kawabata S, Hiraoka J, Fujiwara T, etal. Oral passive immunization against dental caries in rats by use of hen egg yolk antibodies specific for cell-associated glucosyltransferase of Streptococcus mutans. Infect Immun. 1991; 59: 4161–7. [PubMed Abstract] [PubMed CentralFull Text].

 Google Scholar

Kruger C, Pearson SK, Kodama Y, Vacca Smith A, Bowen WH, Hammarstrom L. The effects of egg-derived antibodies to glucosyltransferases on dental caries in rats. Caries Res. 2004; 38: 9–14. [PubMed Abstract].

 Google Scholar