2000 Fiscal Year Final Research Report Summary
Mechanisms of a novel Salmonella virulence gene that involves in intramacrophage survival
| Project/Area Number |
11670277
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Meijo University |
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Principal Investigator |
UCHIYA Keiichi Pharmacy, Meijo University Assistant Professor, 薬学部, 助手 (70168714)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Salmonella / Virulence gene / Effector molecule / Regulation / Macrophage / Survival / IL-10 |
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| Research Abstract |
The spiC gene in the Salmonella Pathogenicity Island 2 (SPI-2) on the Salmonella enterica serovar Typhimurium chromosome is required for intramacrophage survival and systemic infection in mice. I have investigated the regulation of expression and the function of spiC gene according to the project plan of Grant-in-Aid for Scientific Research.
1. The regulation of spiC gene expression : (1) The spiC gene expression was positively regulated by the PhoP/PhoQ system, as well as the ssrA (spiR)/ssrB two-component regulatory genes in the SPI-2. (2) The spiC gene was specifically expressed when the bacteria are in stationary phase of growth, and was positively regulated by the sigma factor RpoS.(3) The spiC gene expression increased with the condition of low Mg^<2+> (10 μM) and low pH (5.0). (4) The expression of spiC gene in S.Typhimurium inside macrophages increased with time after phagocytosis, indicating that the phagosomal environment of macrophages induces the spiC gene expression.
2. The function of SpiC protein : (1) SpiC is a effector translocated into the cytosol of infected macrophages using the type III secretion system of SPI-2. (2) SpiC play an important in intramacrophage survival by interfering with the fusion between the phagosome and lysosomal compartments. Furthermore, when SpiC was expressed inside macrophages using a Sindbis virus system, the normal trafficking was blocked. (3) SpiC also participates in the increase of expression of Interleukin-10, which is known to be a deactivator of macrophages, in macrophages infected with Salmonella. I am planning to examine the relationship between the IL-10 expression and intramacrophage survial.
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