2005 Fiscal Year Final Research Report Summary
Genome Analysis of Emergence Mechanisms of New Enterohemorrhagic Escherichia coli and Genome-Based Drug Research toward HUS Treatment
| Project/Area Number |
16390128
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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, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (80095843)
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| Co-Investigator(Kenkyū-buntansha) |
TANEIKE Ikue Niigata University, Faculty of Medicine, Assistant Teacher, 医学部, 教務補佐員 (50397105)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Enterohemorrhagic Escherichia coli (EHEC) / HUS / Genome analysis / WIM model / Adherence factor / IgA1 protease |
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| Research Abstract |
Infection of children and the elderly with enterohemorrhagic Escherichia coli (EHEC) results in hemolytic uremic syndrome (HUS), a severe complication with a poor prognosis. The type III secretion system (mechanism of intestinal colonization) of EHEC has been considered to be essential for the development of HUS. However, in case of intrafamilinal infection due to serotype O86 EHEC, although the E.coli strains do not have the type III secretion system, infected children developed HUS, and died. In this study, we investigated the molecular genetic properties of serotype O86 EHEC strains. These strains had a 120.73-kb plasmid (pO86A) encoding a diffuse adherence factor (HdaA), and lysogenized a 60.238-kb phage encoding type 2 Shiga toxin (Stx2). pO86A also had the Shigella flexneri type IgA1 protease gene, and conferred resistance to mucosal immunity to serotype O86 EHEC strains. The Stx phage showed properties of the insertion site found only in O86 strains, but not in O157 strains. These results support the hypothesis that in the intestinal tract of a child, serotype O86-specific Stx2 phage is lysogenized into highly-colonizing (diffusely-adhering and IgA1 protease-producing) O86 E.coli strains, resulting in the emergence of new EHEC, causing fatal HUS. It was also concluded that type III secretion is not essential for the development of HUS. Moreover, it is considered that Shiga toxin induces inflammatory cytokines such as IL-6 and IL-8 to cause HUS. We demonstrated that a Chinese herb, anisodamine, and an antimicrobial agent, azityhromycin, inhibited such an inflammatory cytokine induction, most probably blocking the NF-kB activation pathway.
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Research Products
(12 results)
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[Journal Article] A Panton-Valentine leukocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strain, another such strain carrying a multiple-drug resistance plasmid, and other more-typical PVL-negative strains found in Japan.2005
Author(s)
Takizawa Y, Taneike I, Nakagawa S, Oishi T, Nitahara Y, Iwakura N, Ozaki K, Takano M, Nakayama T, Yamamoto T
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Journal Title
J. Clin. Microbiol 43(7)
Pages: 3356-3363
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A Panton-Valentine leukocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strain, another such strain carrying a multiple-drug resistance plasmid, and other more-typical PVL-negative strains found in Japan.2005
Author(s)
Takizawa Y, Taneike I, Nakagawa S, Oishi T, Nitahara Y, Iwakura N, Ozaki K, Takano M, Nakayama T, Yamamoto T
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Journal Title
J.Clin.Microbiol 43(7)
Pages: 3356-3363
Description
「研究成果報告書概要(欧文)」より
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