Elucidation of a novel mechanism for repairing oxidized proteins in the bacterial periplasmic space

• Project/Area Number: 18K05388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38020:Applied microbiology-related
• Research Institution: Shinshu University
• Principal Investigator: OGASAWARA Hiroshi 信州大学, 学術研究院総合人間科学系, 准教授 (30535232)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Escherichia coli / Two-component system / HprS/HprR / ROS / Periplasmic space / Oxidative stress / HprS/R / H2O2 / hydrogen peroxide / Hydrogen peroxide / 大腸菌 / ペリプラズム

Outline of Final Research Achievements

Proteins located in the periplasmic space near by the outermembrane of bacteria are likely to be exposed to reactive oxygen species in the environment and frequently undergoing oxidative damage. Most of the repair mechanisms for oxidized proteins that have been identified and elucidated so far work mainly in the cytoplasm, and the mechanism in the periplasmic space has remained unclear. In this study, we aimed to clarify the molecular mechanisms involved in the activation of HprS, which functions as a sensor for the reactive oxygen species in the periplasmic space of bacteria, and the role of HprS homologues in Gram-negative bacteria.

Academic Significance and Societal Importance of the Research Achievements

本研究は、細菌のペリプラズム空間における酸化的損傷タンパク質の修復機構とその発現誘導の分子メカニズムの解明が主な目的である。これまで細菌ペリプラズム空間で機能するプロテアーゼやシャペロンタンパク質は知られているが、酸化的損傷タンパク質の修復機構は、殆ど不明であった。本研究で機能解析を進めたセンサーキナーゼHprSとその制御下にあるメチオニンスルホキシド還元酵素MsrQPは、グラム陰性細菌に広く保存され、これらは細胞外ROSに対する耐性能付与に重要な役割を果たしていると考えられるため、病原性大腸菌を始めとする多くのグラム陰性細菌の新たな創薬ターゲットとしての可能性も期待できる。

Research Products

• [Journal Article] Novel regulators of the csgD gene encoding the master regulator of biofilm formation in Escherichia coli K-12 (2020)
  • Author(s): Ogasawara H., Ishizuka T., Hotta S., Aoki M., Shimada T., Ishihama A.
  • Journal Title: Microbiology Volume: 166 Issue: 9 Pages: 880-890
  • DOI: 10.1099/mic.0.000947
  • Peer Reviewed
• [Journal Article] Regulatory Role of Pyruvate-Sensing BtsSR in Biofilm Formation by Escherichia Coli K-12 (2019)
  • Author(s): Ogasawara H., Ishizuka T., Yamaji K., Kato Y., Shimada T., Ishihama A.
  • Journal Title: FEMS microbiology letters Volume: 366 Issue: 24
  • DOI: 10.1093/femsle/fnz251
  • Peer Reviewed
• [Journal Article] Genomic SELEX Screening of Regulatory Targets of Escherichia coli Transcription Factors (2018)
  • Author(s): Shimada Tomohiro、Ogasawara Hiroshi、Ishihama Akira
  • Journal Title: Methods in Molecular Biology Volume: 1837 Pages: 49-69
  • DOI: 10.1007/978-1-4939-8675-0_4
  • ISBN: 9781493986743, 9781493986750
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Single-target regulators form a minor group of transcription factors in Escherichia coli K-12 (2018)
  • Author(s): Shimada Tomohiro、Ogasawara Hiroshi、Ishihama Akira
  • Journal Title: Nucleic Acids Research Volume: 46 Issue: 8 Pages: 3921-3936
  • DOI: 10.1093/nar/gky138
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 大腸菌二成分制御系HprS/HprRの次亜塩素酸応答における作用機序 (2020)
  • Author(s): 山路幸太郎、谷口瑠美音、小笠原寛
  • Organizer: 第43回日本分子生物学会年会
• [Presentation] 細菌ペリプラズム空間における過酸化水素感知センサーHprSの機能解析 (2019)
  • Author(s): 山路幸太郎、浦野浩行、小笠原寛
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] 大腸菌K-12株のゲノム転写制御ネットワークにおけるSingle-target regulatorsの機能解析 (2018)
  • Author(s): 島田友裕、小笠原寛、石浜明
  • Organizer: 第41回日本分子生物学会年会