Role of P2X7 receptor on C. perfringens beta-toxin-induced pathogenesis
| Project/Area Number |
16K08794
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
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| Research Collaborator |
Takehara Masaya
Kobayashi Keiko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | ウエルシュ菌 / β毒素 / P2X7受容体 / 病原性 / ウエルシュ菌β毒素 / 腸管毒性 / Pannexin1 / 細胞毒性 / オリゴマー |
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| Outline of Final Research Achievements |
For the first time, we have found that β-toxin produced by Clostridium perfringens type C, which is the cause of necrotizing enteritis, acts on the P2X7 receptor of host cells to develop toxicity. In this study, we clarified the pathogenesis of the toxin, and established the research base to expand to therapeutic application of this infection. 1) Cytotoxic mechanism of β-toxin: After acting on the P2X7 receptor of host cells, it was found that β-toxin damages the cell via the pannexin 1 involved in ATP release. 2) β-toxin-induced Intestinal injury: In the mouse ileal loop test, the toxin induced disruption of intestinal tissue, which revealed that the P2X7 receptor is involved. 3) Development of therapeutic agents for the toxin: It was found that the mouse lethal activity and enteric injury of β-toxin are suppressed by administration of BBG, which is a P2X7 receptor inhibitor, to be candidates for therapeutic agents.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトの壊疽性腸炎の原因であるC型ウエルシュ菌β毒素は、日本においては豚などの家畜に感染し、経済的な損失が懸念されている。本毒素の作用メカニズムが解明されれば、本菌による感染症の克服につながる。本研究では、β毒素の細胞障害作用や腸管障害作用を検討し、ATPの受容体の1つであるP2X7受容体に本毒素が作用して、障害を引き起こすことを明らかにした。さらに、P2X7受容体の阻害薬が、本毒素の作用を抑制することが判明した。以上より、本感染症の治療薬に候補が見出され、今後の応用が期待される。
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system.2018
Author(s)
Zeniya S, Kuwahara H, Daizo K, Watari K, Kondoh M, Yoshida-Tanaka K, Kaburagi H, Asada K, Nagata T, Nagahama M, Yagi K, Yokota T
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Journal Title
J. Control Release 283, 126-134 (2018)
Volume: 283
Pages: 126-134
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Angubindin-1, a novel paracellular absorption enhancer acting at the tricellular tight junction.2017
Author(s)
Krug SM, Hayaishi T, Iguchi D, Watari A,Takahashi A, Fromm M, Nagahama M, Takeda H, Okada Y,Sawasaki T, Doi T, Yagi K, Kondoh M
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Journal Title
J Control Release
Volume: 260
Pages: 1-11
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cellular entry of Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin.2017
Author(s)
Takehara, M., Takagishi, T., Seike, S., Oda, M., Sakaguchi, Y., Hisatsune, J., Ochi, S., Kobayashi, K., Nagahama, M.
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Journal Title
Toxins.
Volume: 9(8)
Pages: 247-247
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 光親和性標識体を用いたネオビブサニン類の受容体探索2018
Author(s)
岸本卓, 清水奈津美, 柳本剛志, 柳井翠, 小松加奈, 高岸照久, 葛西祐介,竹原正也, 松井敦聡, 久保美和, 山本博文, 永浜政博, 喜多紗斗美, 赤木正明, 福山愛保, 今川洋
Organizer
日本薬学会 第138年会（金沢）
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