| Project/Area Number |
25460554
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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 |
Bacteriology (including mycology)
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Ikebe Tadayoshi 国立感染症研究所, 細菌第一部, 主任研究官 (20333362)
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| Co-Investigator(Renkei-kenkyūsha) |
ATO Manabu 国立感染症研究所, 免疫部, 部長 (20392318)
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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 |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 劇症型溶血性レンサ球菌感染症 / レンサ球菌 / 細菌 / 遺伝子 / A群レンサ球菌 / 遺伝子変異 |
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| Outline of Final Research Achievements |
Streptococcus pyogenes (group A Streptococcus; GAS) is a widespread human pathogen and causes streptococcal toxic shock syndrome (STSS). STSS isolates have been previously shown to have high frequency mutations in the csrS/csrR (covS/covR) and/or rgg (ropB) genes, which are negative regulators of virulence. However, these mutations were found at low frequencies in emm1-genotyped isolates, the most prevalent STSS genotype. We sought to detect causal mutations of enhanced virulence in emm1 isolates lacking mutation(s) in the csrS/csrR and rgg genes. Two mutations associated with elevated virulence were found in the sic (a virulence gene) promoter and the csrR promoter. In vivo contribution of the sic promoter to pathogenicity and lethality was confirmed in a GAS mouse model. Frequency of the sic promoter mutation was significantly higher in STSS emm1 isolates than in non-invasive STSS isolates. Thus, this mutation plays a key role in the dynamics of virulence and STSS pathogenesis.
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