Construction of a New Fusion Anti-caries DNA Vaccine

2009 ◽  
Vol 88 (5) ◽  
pp. 455-460 ◽  
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.

Role of sweeteners in the etiology and prevention of dental caries

2002 ◽  
Vol 74 (7) ◽  
pp. 1293-1300 ◽  
Author(s):  
Shigeyuki Hamada
Keyword(s):  
Dental Caries ◽  
Mutans Streptococci ◽  
Tooth Surface ◽  
Surface Attachment ◽  
Epidemiological Surveys ◽  
High Prevalence ◽  
Insoluble Glucan ◽  
Causative Agents ◽  
Glucan Synthesis ◽  
Major Factors

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.

A DNA Vaccine Encoding a Cell-surface Protein Antigen of Streptococcus mutans Protects Gnotobiotic Rats from Caries

2002 ◽  
Vol 81 (11) ◽  
pp. 784-787 ◽  
Author(s):  
M.W. Fan ◽  
Z. Bian ◽  
Z.X. Peng ◽  
Y. Zhong ◽  
Z. Chen ◽  
...  
Keyword(s):  
Dental Caries ◽  
Cell Surface ◽  
Streptococcus Mutans ◽  
Dna Vaccine ◽  
Recombinant Dna ◽  
Surface Protein ◽  
Protein Antigen ◽  
Cell Surface Protein ◽  
Igg Antibody ◽  
A Cell

A cell-surface protein antigen (PAc) of Streptococcus mutans is considered a virulence factor because it may mediate initial attachment of Streptococcus mutans to tooth surfaces. Thus, inhibiting PAc is predicted to provide protection against caries. To develop vaccines against dental caries, we constructed a DNA vaccine, pCIA-P, which encodes two high-conservative regions of PAc. Expression of the recombinant protein was obtained in eukaryotic cells in vitro and in vivo. In this report, we provide evidence that fewer caries lesions, and high levels of PAc-specific salivary IgA antibody and serum IgG antibody, were observed in gnotobiotic rats following targeted salivary gland (TSG) administration of pCIA-P. This study shows that the recombinant DNA vaccine pCIA-P could induce protective anti-caries immune responses and that TSG immunization is a promising strategy for the inhibition of dental caries.

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

2000 ◽  
Vol 68 (5) ◽  
pp. 2698-2703 ◽  
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.

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

2016 ◽  
Vol 10 (1) ◽  
pp. 360-366 ◽  
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.

Protein Antigen in Serotype k Streptococcus mutans Clinical Isolates

2008 ◽  
Vol 87 (10) ◽  
pp. 964-968 ◽  
Author(s):  
K. Nakano ◽  
R. Nomura ◽  
H. Nemoto ◽  
J. Lapirattanakul ◽  
N. Taniguchi ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Dental Caries ◽  
Cell Surface ◽  
Streptococcus Mutans ◽  
Western Blotting ◽  
Surface Protein ◽  
Clinical Isolates ◽  
Cell Surface Protein ◽  
Western Blotting Analysis ◽  
Blotting Analysis

Streptococcus mutans, a major pathogen of dental caries and infective endocarditis, is classified into serotypes c, e, f, and k, with serotype k strains recently reported to be frequently detected in persons with infective endocarditis. Thus, we hypothesized that common properties associated with infective endocarditis are present in those strains. Fifty-six oral S. mutans strains, including 11 serotype k strains, were analyzed. Western blotting analysis revealed expression of the 3 types of glucosyltransferases in all strains, while expression of the approximately 190-kDa cell-surface protein (PA) was absent in 12 strains, among which the prevalence of serotype k (7/12) was significantly high. Furthermore, cellular hydrophobicity and phagocytosis susceptibility were lower in the group of serotype k strains. These results indicate that the absence of PA expression, low cellular hydrophobicity, and phagocytosis susceptibility are common bacterial properties associated with serotype k strains, which may be associated with virulence for infective endocarditis.

scholarly journals Bis-methionyl Coordination in the Crystal Structure of the Heme-binding Domain of the Streptococcal Cell Surface Protein Shp

2007 ◽  
Vol 374 (2) ◽  
pp. 374-383 ◽  
Author(s):  
Roman Aranda ◽  
Chad E. Worley ◽  
Mengyao Liu ◽  
Eduard Bitto ◽  
M. Susan Cates ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cell Surface ◽  
Surface Protein ◽  
Binding Domain ◽  
Heme Binding ◽  
Cell Surface Protein

scholarly journals Passive Immunization with Bovine Milk Containing Antibodies to a Cell Surface Protein Antigen-Glucosyltransferase Fusion Protein Protects Rats against Dental Caries

2002 ◽  
Vol 70 (5) ◽  
pp. 2721-2724 ◽  
Author(s):  
Morihide Mitoma ◽  
Takahiko Oho ◽  
Naoko Michibata ◽  
Kaoru Okano ◽  
Yutaka Nakano ◽  
...  
Keyword(s):  
Cell Surface ◽  
Bovine Milk ◽  
Passive Immunization ◽  
Surface Protein ◽  
Protein Antigen ◽  
Cell Surface Protein ◽  
Rich Region ◽  
A Cell ◽  
Colonization Factors ◽  
Glucan Binding Domain

ABSTRACT Cell surface protein antigen (PAc) and glucosyltransferases (GTF) of Streptococcus mutans are major colonization factors of the organism. We prepared bovine milk containing antibodies against a fusion of the saliva-binding alanine-rich region of PAc with the glucan-binding domain of GTF-I. This study examined the effect of the immune milk on the cariogenicity of S. mutans in a rat model. Concentrated immune milk was fed to rats once a day for 55 days. The group that received immune milk had significantly less caries development than controls.

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