Role of P2X7 receptor on C. perfringens beta-toxin-induced pathogenesis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08794
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Tokushima Bunri University
• Principal Investigator: Masahiro Nagahama 徳島文理大学, 薬学部, 教授 (40164462)
• Research Collaborator: Takehara Masaya ; Kobayashi Keiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ウエルシュ菌 / β毒素 / P2X7受容体 / 病原性

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.

Free Research Field

細菌学

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。