| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Streptococcal toxic shock syndrome has been occurred since around 1990 and the mechanism of the disease is considered to be tightly connected the virulent proteins. We analyzed the mechanism of the production of virulent proteins of Streptococus pyogenes, especially by using two-dimensional gel electrophoresis.
1. We established the mga-associated gene knock out strain. This gene is located near Mga coding region. Mga has been studied extensively because it is one of the important regulators. In this mutant, Sic production increased. The mechanism was proposed that it interacts with Mga protein and influence the binding capacity to the sic promoter.
2. We established transcription termination regulator nusG knock out strain. The strain produced more NAD-glycohydrolase, Streptolysin O, and Sic protein.
3. We examined the effect of clindamycin which is recommended for the therapy of streptococcal toxic shock-syndrome because it was reported that this antibiotic suppresses the production of virulent proteins. We found that sublethal dose administration of clindamycin increased some exoproteins, especially, Nga, Slo and Sic, when it was administrated at the beginning of the bacteria culture. However the effect was greatly dependent on the administration timing, that is, the effect differed according to the growth phase of bacteria.
4. We established signal peptidase I (sipC and lsp) knock out strains and found LSP is involved in Sec pathway ; on the other hand SipC is not. But some secreted proteins are influenced with both proteins.
5. Different 2DE profiles of exoproteins of M1 type clinical isolate of S.pyogenes were detected. The big difference is the production of SpeB and Sic. By the sequence analysis and gene knock out studies, the difference could be dependent the amino acid difference of CsrS, one of the important two-component regulator.
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