2007 Fiscal Year Final Research Report Summary
Functional analysis of virulence factor involved in intracellular survival and development to new drug cure
| Project/Area Number |
17590403
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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 Meijo University, Pharmacy, Assistant professor (70168714)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Salmonella / SPI-2 / spiC gene / Flagellum / FliC / Macrophage / SOCS-3 / Signal transduction |
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| Research Abstract |
SpiC is a virulence factor encoded within Salmonella pathogenicity island 2, which is required for survival within macrophages and systemic infection in mice. We previously reported that a strain carrying a mutation in the spiC gene is unable to survive within macrophages and has greatly reduced virulence in mice. Furthermore, gene expression analysis using a cDNA array showed the involvement of SpiC in the expression of suppressor of cytokine signaling 3 (SOCS-3).
In the present study, we have investigated the significance of SOCS-3 expression and the mechanism by which SpiC mediates the activation of signal transduction pathways in macrophages after Salmonella enterica serovar Typhimurium infection. Proteomic analysis showed that the level of FliC protein, a component of the flagellar filaments, was lower in the culture supernatant of a spiC mutant strain than in the supernatant from wild-type Salmonella. Furthermore, transcription of the fliC gene was greatly reduced by a mutation of the spiC gene. Electron microscopy revealed that the formation of flagellar filaments is defective in a spiC mutant strain. The level of SOCS-3 in J774 macrophages was lower when they were infected with thefliC mutant than with wild-type Salmonella. FliC participated in the activation of MAPK pathways in Salmonella-infected macrophages, leading to the up-regulation of SOCS-3 expression. Collectively, these results suggest that SpiC is required for FliC expression, which is needed for the assembly of flagellar filaments and which plays a significant role in the SpiC-dependent activation of MAPK pathways in Salmonella-infected macrophages. Thus, it is likely that SpiC plays a role in Salmonella virulence by making use of the flagellar system.
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