| Project/Area Number |
18580184
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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 |
General fisheries
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| Research Institution | Kyoto Pharmaceutical University (2007)
Hiroshima University (2006) |
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Principal Investigator |
OKUDA Jun Kyoto Pharmaceutical University, 薬学部, Associate Professor (90334276)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAI Toshihiro Hiroshima University, 生物圏科学研究科, Professor (60164117)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,670,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Edwardsiella tarda / the type III secretion system / antiphagocytosis / Invasion to epithelial cell / pathogenicity / 新規エフェクター / エフェクター / 食菌抵抗性 |
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| Research Abstract |
(1) Intracellular replication of Edwardsiella tarda in murine macrophage is dependent on the type III secretion system
Edwardsiella tarda is a pathogen with a broad host range that infects both animals and humans. Resistance to phagocytic killing may be involved in the pathogenicity of this bacterium. We showed that intracellular replication of E. tarda in murine macrophages is dependent on the type III secretion system and induces an anti-apoptotic effect by up-regulating anti-apoptotic NF-kappaB target genes. The wild-type strain replicates within the phagosomal membrane of macrophages ; whereas the type III mutant does not.
(2) Microarray analysis
Microarray analysis shows the mRNA expression level of NF-kappaB target genes (e.g. pro-inflammatory cytokines and anti-apoptotic genes) in macrophages infected with the wild-type strain were up-regulated compared to macrophages infected with the type III mutant. Up-regulation of anti-apoptotic NF-kappaB target genes is responsible for the an
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ti-apoptotic activity of E. tarda and is required for intracellular replication in murine macrophages
(3) The type III secretion system-dependent repression of NF-kappaB activation to the intracellular growth of Edwardsiella tarda in human epithelial cells
We next showed that the TTSS is also needed for intracellular growth of the bacterium in human epithelial cells (Hep-2). However, different from the previous microarray analyses on murine macrophages, upregulation of the mRNA expression level of NF-kappaB target genes was not detected in the infected Hep-2 cells. The wild-type E tarda, but not its TTSS mutant, actually repressed the tumor necrosis factor alpha-dependent NF-kappaB activation in an NF-kappaB reporter gene assay. These results suggest TTSS-dependent repression of the NF-kappaB activation in Hep-2 cells infected with E. tarda.
Taken together, these results suggest that drug or vaccine specifically targeting the type III secretion system of this bacterium may contribute to decreasing the industrial loss caused by E. tarda infection to cultured fish such as red sea bream and Japanese flounder. Less
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