| Project/Area Number |
07457070
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SASAKAWA Chihiro The University of Tokyo, Institute of Med.Science, Professor, 医科学研究所, 教授 (70114494)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Nobuhiko The University of Tokyo, Institute of Med.Science, Research Associate, 医科学研究所, 助手 (80194364)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1995: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | Shigellosis / Shigella / Pathogenicity / infection / invasiveness / integrin / 細菌病原性 / 細胞外マトリックス |
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| Research Abstract |
Ipa proteins secreted from Shigella play a crucial role in the invasion of epithelial cells by the bacteria, in which they could be directly involved in eliciting rearrangement of host actin cytoskeletons at the site of bacterial attachment of the epithelial cells. However, the mechanisms underlying the Ipa secretion or the involvement in the invasion have been remain unclear. In this study, we found the following three properties of Ipa proteins : (1 ) Release of Ipa proteins into the external medium from Shigella surface is triggered upon contact of the bacterium with the epithelial cells or the extracellular matrix such as fibronectin, laminine, or collargen type IV,and the released Ipa proteins from the bacterial surface is essential for expressing the invasive phenotype. (2) In a Shigella invasive system with CHO cell monolayrs, the released Ipa proteins are capable of interacting directly with alpha5beta1 integrin. The invasive capacity of Shigella for CHO cells increased as levels of alpha5beta1 integrin are elevated. When CHO cells are infected with Shigella, the tyrosine phosphorylation both of FAK and paxillin is stimulated. At the site of attachment of Shigella to CHO cells, alpha5beta1 integrin converged with polymerization of actin. (3) The invasion capacity of Shigella for CHO cells and other optithelial cells are greatly reduced when treated with C3 trandferase. Conversely, uptake of bacteria by CHO cells is promoted upon microinjection of an activated rho variant, Val14RhoA.These results indicate that the capacity of Ipa proteins to interact with alpha5beta1 integrin is an important Shigella factor in the invasion process, and that the cellular signal transduction regulated by rho is essential for Shigella invasion of epithelial cells.
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