Analysisi of EGFR-signaling pathway in Mycoplasma pneumoniae infection

• Project/Area Number: 15K09589
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Kurume University
• Principal Investigator: KUWANO KOICHI 久留米大学, 医学部, 教授 (60215118)
• Co-Investigator(Kenkyū-buntansha): 山本 武司 久留米大学, 医学部, 助教 (20632566) ; 木田 豊 久留米大学, 医学部, 准教授 (30309752)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: マイコプラズマ肺炎 / EGFR / 細胞死 / Mycoplasma pneumoniae / ＥＧＦＲ / 過酸化水素 / 持続感染 / TLR / Mpn573 / TLR2 / サイトカイン / トランス活性化 / 炎症 / IL-8

Outline of Final Research Achievements

The excessive immune responses are thought to be responsible for the pathophysiology of Mycoplasma pneumoniae(Mp) pneumonia. Although TLR2 plays a predominant role in the inflammatory responses against Mp, the inflammatory responses still observed in TLR2-deficient mice. In this study, we investigated the involvement of EGFR in the TLR2-independent immune responses.
Since the membrane fraction of Mp induces EGFR activation, we first examined the mycoplasmal protein binding to EGFR. We found that Mpn573 binds to EGFR, but unfortunately the protein was unable to activate EGFR. Moreover, cytoadherence that is thought to be important for the progression of Mp pneumonia was not essential for the activation of EGFR. On the other hand, we found that Mp has an ability to regulate the infected cell death, and the ability may allow the EGFR activating factor of Mp to act on the infected cells for a long time.

Research Products

• [Journal Article] Mpn491, a secreted nuclease of Mycoplasma pneumoniae, plays a critical role in evading killing by neutrophil extracellular traps (2017)
  • Author(s): Yamamoto, T., Kida, Y., Sakamoto, Y., Kuwano, K.
  • Journal Title: Cell. Microbiol. Volume: 19 Issue: 3 Pages: 1-11
  • DOI: 10.1111/cmi.12666
  • Peer Reviewed / Open Access
• [Journal Article] 肺炎マイコプラズマの分泌型ヌクレアーゼは好中球のNETsを分解する (2015)
  • Author(s): 山本武司、桑野剛一、木田豊
  • Journal Title: 日本マイコプラズマ学会雑誌 Volume: 42 Pages: 57-58
• [Presentation] Mpn491, a secreted nuclease of Mycoplasma pneumoniae, plays a critical role in evading killing by neutrophil extracellular traps. (2017)
  • Author(s): Koichi Kuwano
  • Organizer: 2017CSHAC Bacterial infection & host defense
  • Int'l Joint Research
• [Presentation] Mycoplasma pneumoniaeの分泌型Nucleaseは好中球NETsによる殺菌の回避に関与する (2016)
  • Author(s): 山本武司、桑野剛一、木田豊、坂本勇一
  • Organizer: 第８９回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2016-03-24
• [Book] 標準微生物学 (2018)
  • Author(s): 桑野剛一 （分担）
  • Total Pages: 6
  • Publisher: 医学書院
  • ISBN: 9784260034562
• [Book] 最新マイコプラズマ学 日本マイコプラズマ学会編 (2016)
  • Author(s): 桑野剛一
  • Publisher: 近代出版