| Project/Area Number |
25670797
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Okayama University |
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Principal Investigator |
Kokeguchi Susumu 岡山大学, 医歯(薬)学総合研究科, 准教授 (10144776)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA HIROSHI 大阪歯科大学, 歯学部, 教授 (00274001)
TAMAKI NAOFUMI 徳島大学, 大学院医歯薬学研究部, 准教授 (20335615)
KARIYAMA REIKO 岡山学院大学, 人間生活学部, 准教授 (40112148)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 感染症 / 歯学 / 細菌 / ゲノム / 抗菌薬 / 抗生物質 |
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| Outline of Final Research Achievements |
The bacterial enzyme LpxC catalyzes the first step of LPS biosynthesis in Gram-negative bacteria. It is essential for growth and viability of Gram-negative bacteria, which has no sequence homology with any mammalian protein. So, it is expected a promising target in the development of novel antibiotics against Gram-negative bacteria.
In this study, antibacterial activity of CHR-12, which is one of LpxC inhibitors, on various oral bacteria were investigated. CHR-12 was highly effective in suppressing the growth of A. actinomycetemcomitans, F. nucleatum, E. corrodens and C. rectus, which LpxC orthologs structure were resemble to E. coli LpxC, but not of P. gingivalis, P. intermedia, P. nigrescens and C. ochracea. These LpxC orthologs were different from E. coli LpxC. CHR-12 was also inhibit A. actinomycetemcomitans biofilm formation. P. gingivalis recombinant LpxC for X-ray crystal structural study was prepared, but it is difficult to assay the LPS synthesis by fluorescence-based method.
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