Gallotannins Inhibit Growth, Water-insoluble Glucan Synthesis, and Aggregation of Mutans Streptococci

Dental caries is a multifactorial disease that is caused by an interplay of three major factors, i.e., teeth, cariogenic bacteria, and fermentable sugars. Streptococcus mutans and S. sobrinus, collectively termed mutans streptococci (MS), are principal causative agents of dental caries. Initial MS-tooth surface attachment is followed by firm and irreversible adhesion of MS to the tooth surface, accompanied by the synthesis of water-insoluble glucan from sucrose via enzymatic action of glucosyltransferases (GTases). MS induce severe dental caries in rats fed on a high-sucrose diet. Epidemiological surveys indicate that frequent sucrose intakes are associated with high prevalence of dental caries in humans. In contrast, dietary sucrose restrictions and/or use of nonfermentable sucrose substitutes clearly influence the GTase activities of MS, resulting in decreased caries development. Structural isomers of sucrose (i.e., disaccharides composed of glucose and fructose with different linkages) will not function as substrates for GTases of MS, nor be utilized as energy sources by MS. Palatinose and trehalulose are included in this category, and are produced in commercial scales in Japan. Glucose oligomers containing α-1, 6 and/or α-1, 4 linkages are found to inhibit glucan synthesis by MS from sucrose, although these oligomers are hydrolyzed by MS to release acids. Lastly, sugar alcohols, including maltitol and palatinit, are useful as noncaries-inducing sweeteners.

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Inhibition by Hop Bract Polyphenols of Cellular Adherence and Water-insoluble Glucan Synthesis of Mutans Streptococci

Bioscience Biotechnology and Biochemistry ◽

10.1271/bbb.61.332 ◽

1997 ◽

Vol 61 (2) ◽

pp. 332-335 ◽

Cited By ~ 55

Author(s):

Motoyuki Tagashira ◽

Keiko Uchiyama ◽

Tomoaki Yoshimura ◽

Masayuki Shirota ◽

Nobuo Uemitsu

Keyword(s):

Mutans Streptococci ◽

Insoluble Glucan ◽

Glucan Synthesis

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Coimmunization with Complementary Glucosyltransferase Peptides Results in Enhanced Immunogenicity and Protection against Dental Caries

Infection and Immunity ◽

10.1128/iai.68.5.2698-2703.2000 ◽

2000 ◽

Vol 68 (5) ◽

pp. 2698-2703 ◽

Cited By ~ 20

Author(s):

Martin A. Taubman ◽

Daniel J. Smith ◽

Cynthia J. Holmberg ◽

Jean W. Eastcott

Keyword(s):

Dental Caries ◽

Functional Significance ◽

Serum Antibody ◽

Mutans Streptococci ◽

Streptococcus Sobrinus ◽

Insoluble Glucan ◽

Glucan Synthesis ◽

The Individual ◽

Antibody Levels

ABSTRACT Peptide constructs from the catalytic (CAT) and glucan-binding (GLU) regions of the mutans streptococcal glucosyltransferase enzymes (GTF) can provide immunity to dental caries infection. A strategy of coimmunization was tested to determine whether protection could be enhanced. Rats were immunized with one of the previously described peptide constructs from the CAT or GLU region of the GTF of mutans streptococci or coimmunized with a combination of these constructs (CAT-GLU). Coimmunized animals demonstrated significantly higher serum immunoglobulin G (IgG) and salivary IgA antibody levels to CAT or GTF than rats immunized with either construct alone. To assess the functional significance of coimmunization with these constructs, animals were immunized as above or with Streptococcus sobrinus GTF and then infected with S. sobrinus to explore the effects of immunization on immunological, microbiological, and disease (dental caries) parameters. Serum antibody from the communized group inhibited S. sobrinus GTF-mediated insoluble glucan synthesis in vitro above that of the individual-construct-immunized groups. Immunization with CAT or GLU constructs resulted in significantly reduced dental caries after infection with S. sobrinus compared with sham-immunized animals. Coimmunization produced greater reductions in caries than after immunization with either CAT or GLU. Also, significant elevations in lymphocyte proliferative responses to CAT, GLU, and GTF were observed after coimmunization with CAT-GLU compared with the responses after immunization with the individual constructs. The results suggested that increased numbers of memory T cells, which could proliferate to CAT, were generated by coimmunization. The experiments support the functional significance of these GTF domains in dental caries pathogenesis and present coimmunization as a simple alternative to intact GTF to enhance protective immunity against cariogenic microorganisms.

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Construction of a New Fusion Anti-caries DNA Vaccine

Journal of Dental Research ◽

10.1177/0022034509336727 ◽

2009 ◽

Vol 88 (5) ◽

pp. 455-460 ◽

Cited By ~ 9

Author(s):

Y. Niu ◽

J. Sun ◽

M. Fan ◽

Q.-A. Xu ◽

J. Guo ◽

...

Keyword(s):

Dental Caries ◽

Dna Vaccine ◽

Surface Protein ◽

Binding Domain ◽

Mutans Streptococci ◽

Cell Surface Protein ◽

Insoluble Glucan ◽

Antigenic Domains ◽

Glucan Synthesis ◽

Glucan Binding Domain

Mutans streptococci (MS) are generally considered to be the principal etiological agent of dental caries. MS have two important virulence factors: cell- surface protein PAc and glucosyltransferases (GTFs). GTFs have two functional domains: an N-terminal catalytic sucrose-binding domain (CAT) and a C-terminal glucan-binding domain (GLU). A fusion anti-caries DNA vaccine, pGJA-P/VAX, encoding two important antigenic domains, PAc and GLU, of S. mutans, was successful in reducing the levels of dental caries caused by S. mutans in gnotobiotic animals. However, its protective effect against S. sobrinus infection proved to be weak. Does the DNA vaccine need an antigen of S. sobrinus to enhance its ability to inhibit infection? To answer this question, in this study, we cloned the catalytic ( cat) fragment of S. sobrinus gtf-I, which demonstrated its ability to inhibit water-insoluble glucan synthesis by S. sobrinus, into pGJA-P/VAX to produce a new anti-caries DNA vaccine.

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Functional and Immunogenic Characterization of Two Cloned Regions of Streptococcus mutansGlucosyltransferase I

Infection and Immunity ◽

10.1128/iai.67.2.810-816.1999 ◽

1999 ◽

Vol 67 (2) ◽

pp. 810-816 ◽

Cited By ~ 30

Author(s):

Christina Jespersgaard ◽

George Hajishengallis ◽

Terrence E. Greenway ◽

Daniel J. Smith ◽

Michael W. Russell ◽

...

Keyword(s):

Mutans Streptococci ◽

Water Soluble ◽

Antibody Activity ◽

Amino Acid Residues ◽

Igg Antibody ◽

Mucosal Antibody ◽

Insoluble Glucan ◽

Iga Antibody ◽

Glucan Synthesis

ABSTRACT Glucosyltransferase (GTF) enzymes of mutans streptococci are considered virulence factors due to their ability to synthesize adhesive glucans, which facilitate cell-to-cell adherence and accumulation. In this study we report the cloning, expression, and characterization of the catalytic (CAT) and glucan-binding (GLU) domains of S. mutans GTF-I encoded by gtfB. The CAT and GLU polypeptides represent amino acid residues 253 to 628 and 1183 to 1473, respectively, of S. mutans GTF-I. Antibodies to recombinant CAT and GLU were generated in rabbits and purified by affinity chromatography. Purified anti-CAT antibodies significantly inhibited water-insoluble glucan synthesis by S. mutans andS. sobrinus GTFs (P < 0.0001 andP < 0.05, respectively). The purified anti-GLU antibodies significantly inhibited both water-insoluble and water-soluble glucan synthesis by S. mutans GTFs (P < 0.0001 and P < 0.05, respectively). These results demonstrate that anti-CAT and anti-GLU antibodies are capable of inhibiting a variety of GTF activities. Since antibodies to S. mutans in saliva are implicated in protection against disease, we next assessed the ability of CAT and GLU polypeptides to induce mucosal antibody responses in mice. Intranasal (i.n.) immunization of mice with CAT showed significantly (P < 0.005) elevated levels of specific immunoglobulin G (IgG) antibody activity in serum and specific IgA antibody activity in serum, saliva, vaginal washes, and fecal samples. GLU immunized animals showed significantly (P < 0.005) elevated levels of specific IgA antibody activity in serum and vaginal secretions. Taken together, these results demonstrate that the recombinant CAT and GLU polypeptides are effective in inducing both mucosal and systemic immune responses. The ability of these polypeptides to induce a mucosal IgA immune response in mice after i.n. immunization supports their use as subunit vaccine candidates in the development of an anticaries vaccine.

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Streptococcus mutans Dextransucrase: Functioning of Primer Dextran and Endogenous Dextranase in Water-Soluble and Water-Insoluble Glucan Synthesis

Infection and Immunity ◽

10.1128/iai.16.2.637-648.1977 ◽

1977 ◽

Vol 16 (2) ◽

pp. 637-648 ◽

Cited By ~ 42

Author(s):

Greg R. Germaine ◽

Susan K. Harlander ◽

Woon-Lam S. Leung ◽

Charles F. Schachtele

Keyword(s):

Streptococcus Mutans ◽

Water Soluble ◽

Insoluble Glucan ◽

Glucan Synthesis

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Cationic Lipid Content in Liposome-Encapsulated Nisin Improves Sustainable Bactericidal Activity against Streptococcus mutans

The Open Dentistry Journal ◽

10.2174/1874210616021001360 ◽

2016 ◽

Vol 10 (1) ◽

pp. 360-366 ◽

Cited By ~ 4

Author(s):

Kazuo Yamakami ◽

Hideaki Tsumori ◽

Yoshitaka Shimizu ◽

Yutaka Sakurai ◽

Kohei Nagatoshi ◽

...

Keyword(s):

Dental Caries ◽

Streptococcus Mutans ◽

Cationic Lipid ◽

Cationic Liposome ◽

Bactericidal Effect ◽

Insoluble Glucan ◽

Inhibitory Efficiency ◽

Bactericidal Activities ◽

Glucan Synthesis ◽

Sustained Inhibition

An oral infectious disease, dental caries, is caused by the cariogenic streptococci Streptococcus mutans. The expected preventive efficiency for prophylactics against dental caries is not yet completely observed. Nisin, a bacteriocin, has been demonstrated to be microbicidal against S. mutans, and liposome-encapsulated nisin improves preventive features that may be exploited for human oral health. Here we examined the bactericidal effect of charged lipids on nisin-loaded liposomes against S. mutans and inhibitory efficiency for insoluble glucan synthesis by the streptococci for prevention of dental caries. Cationic liposome, nisin-loaded dipalmitoylphosphatidylcholine/phytosphingosine, exhibited higher bactericidal activities than those of electroneutral liposome and anionic liposome. Bactericidal efficiency of the cationic liposome revealed that the vesicles exhibited sustained inhibition of glucan synthesis and the lowest rate of release of nisin from the vesicles. The optimizing ability of cationic liposome-encapsulated nisin that exploit the sustained preventive features of an anti-streptococcal strategy may improve prevention of dental caries.

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