| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
Infective endocarditis is an infection of the heart valves that causes the vegetation formation on the inner layer of the heart, sepsis, and thromboembolism. While infective endocarditis occurs in apparently healthy people, certain congenital heart defects increase its risk. Then, it needs to administrate of antibacterial agents to high-risk patient before medical treatment accompanied with bleeding. Unfortunately, there are few effects of administration of antibacterial agents before dental treatment. In this study, we identified a novel preventive agent for infective endocarditis. Streptococcus gordonii is one of viridans group streptococci and component of the normal microbial flora of human oral cavity. It plays significant roles as pioneer colonizers in the development of dental plaque. In addition, S. gordonii is also well known for its ability to colonize damaged heart valves and is the most frequently identified bacteria as primary etiological agents of infective endocarditis. An Hsa, is a surface protein of S. gordonii and binds to α2-3-link sialic acid-containing proteins, contributes to pathogenesis of infective endocarditis. In present study, we identified a novel compound to inhibit Hsa sialic acid binding activity. To identify Hsa inhibitors, we performed a screening of 9600 compounds by using hemagglutination assay. We identified 3 compounds as initial hits in the screening. Next, we examined their inhibition activity of GST-HsaNR2 binding to 3’-sialyllactose. Among these candidate compounds, No.2 showed more potent Hsa inhibition activity. In this study, we obtained one of candidate compound from chemical library.
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