| Project/Area Number |
23590147
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | University of Fukui |
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Principal Investigator |
TANAKA Yukie 福井大学, 医学部, 助教 (10197486)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Yutaka 福井大学, 医学部, 教授 (80211522)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
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| Keywords | 微生物感染症学 / 溶血性連鎖球菌 / NADase / SNI |
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| Research Abstract |
The virulence of S. pyogenes is enhanced by toxins like NADase. S. pyogenes additionally express the SNI, which forms an inhibitory complex with NADase. SNI is a target for the development of novel antimicrobials functioning by blocking the bacterium's self-immunity to the NADase toxin. Recent study has shown the crystal structure of NADase-SNI complex to understand the physical basis for NADase inhibition by SNI. We have exploited the conformational information required SNI to bind to NADase to develop novel SNI inhibitors that block immunity of S. pyogenes to NADase and unleash the toxicity of NADase. We have explored the release of NADase toxicity by expressing dominant negative mutants of NADase. Some dominant negative mutants partially inhibited SNI function, resulting in unleashing the weak toxicity of NADase. These results suggest that we should understand more physical basis, particularly in the interaction of NADase-SNI, to improve dominant negative mutants of NADase.
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