The mechanism of paroxysmal cough in pertussis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03485
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Osaka University
• Principal Investigator: Horiguchi Yasuhiko 大阪大学, 微生物病研究所, 教授 (00183939)
• Co-Investigator(Kenkyū-buntansha): 西田 隆司 大阪大学, 微生物病研究所, 助教 (20845200) ; 平松 征洋 大阪大学, 微生物病研究所, 助教 (90739210)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 百日咳 / 百日咳毒素 / Vag8 / エンドトキシン / 咳発作 / ブラジキニン / TRPV1

Outline of Final Research Achievements

In this study, we analyzed the mechanism by which Bordetella pertussis causes severe paroxysmal coughing in host animals. We had previously identified the bacterial virulence factors, pertussis toxin, Vag8, and LOS, as causative agents for paroxysmal cough. Using a mouse coughing model in this study, we clarified that LOS, pertussis toxin (PTx), and Vag8 of the bacteria cooperatively function to cause coughing. Bradykinin induced by LOS sensitized a transient receptor potential ion channel, TRPV1, which acts as a sensor to evoke the cough reflex. Vag8 further increased bradykinin levels by inhibiting the C1 esterase inhibitor, the major downregulator of the contact system, which generates bradykinin. PTx inhibits intrinsic negative regulation systems for TRPV1 through the inactivation of Gi GTPases. Our findings provide a basis to answer long-standing questions on the pathophysiology of pertussis cough.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により百日咳の咳発作のメカニズムが明らかとなった。その成果により、ブラジキニンやTRPV1の作用を阻害することなどによって、百日咳症の患者に多大な負担をかける咳発作に対する原因療法の開発に道が拓かれる可能性が示された。また、研究実施者らが開発したマウスの咳モデルは、咳誘発因子を必要としない覚醒状態の動物の咳を観察できるため、未だ不明な点が多い動物の咳反射メカニズムの解析に大いに役立つと考えられた。