| Project/Area Number |
01440031
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
細菌学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIKAWA Masanosuke The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (80012714)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Nobuhiko As above Assistant, 医科学研究所, 助手 (80194364)
FUKUDA Ichiro As above Assistant, 医科学研究所, 助手 (10242108)
TOBE Toru As above Assistant, 医科学研究所, 助手 (70207596)
SASAKAWA Chihiro As above Associate Professor, 医科学研究所, 助教授 (70114494)
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| Project Period (FY) |
1989 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥28,700,000 (Direct Cost: ¥28,700,000)
Fiscal Year 1992: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1991: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1990: ¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1989: ¥10,600,000 (Direct Cost: ¥10,600,000)
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| Keywords | Shigella / virulence / virulence gene / chromosome / chromosome map / dysentery / 細胞間拡散 / 遺伝子調節 / 細胞性赤痢 / 細胞侵入 / NotI切断地図 / トランスポソン / 病原性 |
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| Research Abstract |
The essential steps leading to dysenteric symptomes by the bacterium Shigella is invasion of colonic epithelial cells, followed by intracellular bacterial multiplication and spread of invading bacteria to adjacent cells. The genetic determinants for the virulence of shigellae are located on the large 230 kb plasmid as well as on the chromosome. Extensive molecular studies have been performed on the plasmid virulence genes by the investigators from many laboratories. We also engaged in such studies in the previous project which resulted in showing that the plasmid encodes virulence-associated functions involved in intracellular invasion, secretion of virulence proteins, intra-and intercellular spreading and regulation of the expression of these plasmid-coded virulence genes. The present project was an extention of these studies aiming to clarify the significance of chromosomal virulence genes in collaboration with the plasmid genes in the pathogenesis of bacillary dysentery. The following are the summary of the results obtained:(1) Avirulent transposon insertion mutants were isolated by random transposon insertion mutagenesis. (2) The virulence-associated phenotypes of these mutants were analysed. (3) A NotI restriction cleavage map of the chromosome was constructed and the above-described mutants were assigned on it. (4) Some of the loci identified by these methods were analysed further genetically and by cellular biological techiques. These virulence-associated regions were found to be involved in either (I) LPS biosynthesis, (II) intracellular multiplication, (III) intercellular spreading, or (IV) regulation of the expression of the virulence genes on the large plasmid. For the regions classified into category (III) or (IV), a detailed analysis was made and the results have already been published as articles or reviews in international journals.
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