2003 Fiscal Year Final Research Report Summary
Development of new antibiotics targeting cell wall biosynthesis of oral pathogenic bacteria
| Project/Area Number |
12557186
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
矯正・小児・社会系歯学
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| Research Institution | Kyushu University (2003)
Nihon University (2000-2002) |
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Principal Investigator |
YAMASHITA Yoshihisa Kyushu University, Faculty of Dental Science, Professor, 歯学研究院, 教授 (20192403)
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| Co-Investigator(Kenkyū-buntansha) |
NOKANO Yoshio Kyushu University, Faculty of Dental Science, Associate Professor, 歯学研究院, 助教授 (80253459)
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| Project Period (FY) |
2000 – 2003
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| Keywords | Streptococcus mutans / Actinobacillus actinomycetemcomitans / cell wall polysaccharide / antibiotics |
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| Research Abstract |
(The 2000 fiscal year)The genes which were related to the synthesis of the capsule polysaccharide of A.actinomycetemconutans(Aa) and cell wall polysaccharide of S.mutans was cloned. Homologous research for the determined sequence of the cloned genes revealed that some of them seemed to encode glycosyltransferases.
(The 2001 fiscal year)The detailed function of each gene product was analyzed with the expressed gene products in Escherichia coli. The result indicated that the gene product of rgpA which is located in the uppermost stream of rgp gene cluster was glycosyltransferase which catalyzes the transfer of the first rhamnose residue. Furthermore, it became to be obvious that the serotype specific cell wall polysaccharide was important for the drug tolerance of S.mutans by comparing the drug tolerance for antibiotics of wild type strain Xc and its mutant strain Xc41.
(The 2002 fiscal year)The genes which encode GDP-D-mannose 4,6-dehydratase and GDP-keto-6-deoxy-D-mannose reductase were
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cloned from the chromosome of the serotype a Aa SUNYaB75 strain. In addition, construction of the variant mutant strains Aa which lost serotype a,c, and d capsular polysaccharide antigens was succeeded by the insertional inactivation. When the tolerance of these variants for several antimicrobial drugs was examined, the sensitivity for bacitracin and vancomycin also slightly increased in any variants.
(The 2003 fiscal year)The antibodies were raised against the rgpC and rgpD gene products of S.mutans expressed in and purified from E.coli. Though S.mutans was cultivated in the presence of the obtained antibodies, it was not possible to effectively inhibit the cell wall polysaccharide synthesis. When the antibody was taken in liposome and added to the culture medium, the interference tendency in the cell wall polysaccharide synthesis was slightly recognized. In case of Aa, antibodies against ABC transporters concerning the synthesis of the polysaccharide were prepared. Every antibodies showed slight blocked effect on capusular polysaccharide synthesis. Less
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[Publications] Engels-Deutsch, M., Pini, A., Yamashita, Y., et al.: "Insertional inactivation of pac and rmlB genes reduces the release of tumor necrosis factor alpha, interleukin-6, and interleukin-8 induced by Streptococcus mutans in monocytic, dental pulp, and periodontal ligament cells"Infect.Immun.. 71. 5169-5177 (2003)
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「研究成果報告書概要(和文)」より
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[Publications] Suzuki, N., Nakano, Y., Yoshida, Y., Nezu, T., Terada, Y., Yamashita, Y., Koga, T.: "Guanosine diphosphate-4-keto-6-deoxy-D-mannose reductase in the pathway for the synthesis of GDP-6-deoxy-D-talose in Actinobacillus actinomycetemcomitans."Eur.J.Biochem.. 269. 5963-5971 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Ozaki, K., Shibata, Y., Yamashita, Y., Yamashita, Y., Tsuda, H., Koga, T.: "A novel mechanism for glucose side-chain formation in rhamnose-glucose polysaccharide synthesis."FEBS Letters. 532. 159-163 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Engels-Deutsch, M., Pini, A., Yamashita, Y., Shibata, Y., Haikel, Y., Scholler-Guinard, M., Klein, J.P.: "Insertional inactivation of pac and rmlB genes reduces the release of tumor necrosis factor alpha, interleukin-6,and interieukin-8 induced by Streptococcus mutans in monocytic, dental pulp, and periodontal ligament cells."Infect.Immun.. 71. 5169-5177 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Shibata, Y., Ozaki, K., Seki, M., Kawato, K., Tanaka, H., Nakano, Y., Yamashita, Y.: "Analysis of loci required for determination of serotype antigenicity in Streptococcus mutans and its clinical utilization."J.Clin.Microbiol.. 41. 4107-4112 (2003)
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「研究成果報告書概要(欧文)」より
