| Project/Area Number |
10470073
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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 | Niigata University |
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Principal Investigator |
YAMAMOTO Tatsuo Niigata University School of Medicine Professor, 医学部, 教授 (80095843)
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| Co-Investigator(Kenkyū-buntansha) |
脇阪 紀子 新潟大学, 医学部, 教務補佐員
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1998: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | Enterohemorrhagic Escherichia coli / O157 : H7 / O128 / EAST1 sequence / Adherence / Enterohemolysin / Anisodamine / Drug resistance / ベロ毒素 / O157 / 感染メカニズム / 溶血毒 |
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| Research Abstract |
・All the enterohemorrhagic Escherichia coli (EHEC) strains possessed the enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1) gene homologues but with two types of mutations. One of the mutation types (type 1) was strongly associated with the large outbreak episodes in 1996 in Japan. In order to detect EHEC O157 : H7 strains with type 1 sequence by PCR, the primer set (SHEAST1a/SHEAST1b) was successfully constructed. The gene homolugue was also found in the Yersinia. pestis IS sequence.
・Out of eleven O157 : H7 outbreaks, only one outbreak revealed infections due to multiple drug-resistant strains which carried an R plasmid. Tetracyclin, streptomycin, and sulfamethoxazole resistance, which was previously described with O157 : H7 strains isolated from a large outbreak as well as sporadic cases in the United States, were also found in Japan with human and bovine isolates. The entire sequences of the drug resiatnce genes were determined.
・Adherent EHEC O157 : H7 cells were enwrapped by elongated cell membrane on cell surface, while enteropathogenic E. coli (EPEC) was enwrapped by the elongated and crowded microvilli on cell surface. These phenomena must reflect distinct infectious mechanisms of EHEC O157 : H7 (toxin producer) and EPEC (non-toxin producer). Enwrapping of EHEC on cell surface by elongated cell membrane may result in effective toxin delivery across the epithelial cells.
・EHEC strains belonging to serotype O128 adhered to epithelial cells in a pattern of chains with a putative novel adherence factor, and produced EHEC-hemolysin to much greater extents than did the other strains.
・EHEC-hemolysin induced the release of interleukin-1β (IL-1β) but not tumor necrosis factor alpha(TNF-α) from human monocyte at subcytocidal concentrations.
Anisodamine suppressed Verotoxin-induced TNF-alpha production via PGE2-dependent mechanism, and decreased the lethality of Verotoxin in mice. Anisodamine could be a potential drug for treatment of HUS.
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