Pathogenicity of hydrogen peroxide produced by oral streptococci

• Project/Area Number: 26463112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Osaka University
• Principal Investigator: Okahashi Nobuo 大阪大学, 歯学研究科, 准教授 (40150180)
• Co-Investigator(Kenkyū-buntansha): 中田 匡宣 大阪大学, 歯学研究科, 准教授 (90444497)
• Co-Investigator(Renkei-kenkyūsha): KUWATA Hirotaka 昭和大学, 歯学部, 教授 (60380523)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ミティス群口腔レンサ球菌 / 過酸化水素 / マクロファージ / 細胞死 / リソソーム / 好中球 / 口腔レンサ球菌 / 細胞内オルガネラ

Outline of Final Research Achievements

Members of the oral mitis group streptococci are dominant colonizers of dental plaque, and causative agents of infective endocarditis.
In the present study, we found that these streptococci produce hydrogen peroxide (H2O2), which is cytotoxic to human macrophages and neutrophils. The cytotoxic effect seemed to be independent of inflammatory responses, because H2O2 was not a potent stimulator of inflammatory cytokines such as TNF-a in macrophages. Our study reveals that streptococcal H2O2 plays as a cytotoxin, and is implicated in the evasion of these streptococci from host defense system by inducing cell death of innate immune cells.

Research Products

• [Journal Article] Microarray analysis of macrophage response to infection with Streptococcus oralis reveals the immunosuppressive effect of hydrogen peroxide (2017)
  • Author(s): H. Matsushima, Y. Kumagai, A. Vandenbon, H. Kataoka, M. Kadena, H. Fukamachi, T. Arimoto, H. Morisaki, N. Fujiwara, N. Okahashi, and H. Kuwata
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 485(2) Issue: 2 Pages: 461-467
  • DOI: 10.1016/j.bbrc.2017.02.048
  • Peer Reviewed / Open Access
• [Journal Article] Streptococcus sanguinis induces neutrophil cell death by production of hydrogen peroxide. (2017)
  • Author(s): Sumioka, R., Nakata, M., Okahashi, N., Li, Y., Wada, S., Yamaguchi, M., Sumitomo, T., Hayashi, M., Kawabata, S.
  • Journal Title: PLoS One Volume: 12 Issue: 2 Pages: e0172223-e0172223
  • DOI: 10.1371/journal.pone.0172223
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] treptococcus pyogenes Endopeptidase O Contributes to Evasion from Complement-mediated Bacteriolysis via Binding to Human Complement Factor C1q (2017)
  • Author(s): Honda-Ogawa M., Sumitomo T., Mori Y., Hamd DT, Ogawa T., Yamaguchi M., Nakata M., Kawabata S.
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 10 Pages: 4244-4254
  • DOI: 10.1074/jbc.m116.749275
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Streptococcus oralis induces lysosomal impairment of macrophages via bacterial hydrogen peroxide. (2016)
  • Author(s): Okahashi, N., Nakata, M., Kuwata, H., Kawabata, S.
  • Journal Title: Infection and Immunity Volume: 84 Issue: 7 Pages: 2042-2050
  • DOI: 10.1128/iai.00134-16
  • Peer Reviewed
• [Journal Article] Evolutionary inactivation of a sialidase ingroup B Streptococcus. (2016)
  • Author(s): Yamaguchi, M., Hirose, Y., Nakata, M., Uchiyama, S., Yamaguchi, Y., Goto, K., Sumitomo, T., Lewis, A., Kawabata, S., Nizet, V.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 28852-28852
  • DOI: 10.1038/srep28852
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions. (2016)
  • Author(s): Sumitomo T, Nakata M, Higashino M, Yamaguchi M, Kawabata S.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 20069-20069
  • DOI: 10.1038/srep20069
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 肺炎球菌と現行ワクチン (2015)
  • Author(s): 中田匡宣、川端重忠
  • Journal Title: 日本歯科医師会雑誌 Volume: 68 Pages: 16-17
• [Journal Article] Hydrogen peroxide contributes to the epithelial cell death induced by the oral mitis group of streptococci. (2014)
  • Author(s): Okahashi N, Sumitomo T, Nakata M, Sakurai A, Kuwata H, and Kawabata S.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: 88136-88136
  • DOI: 10.1371/journal.pone.0088136
  • Peer Reviewed / Open Access
• [Journal Article] Cell wall-anchored nuclease of Streptococcus sanguinis contributes to escape from neutrophil extracellular trap-medicated bacteriocidal activity. (2014)
  • Author(s): Morita C, Sumioka R, Nakata M, Okahashi N, Wada S, Yamashiro T, Hayashi M, Hamada S, Sumitomo T, and Kawabata S.
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: e103125-e103125
  • DOI: 10.1371/journal.pone.0103125
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Streptococcus oralis 産生過酸化水素によるマクロファージの炎症性遺伝子発現制御について (2017)
  • Author(s): 松島瞳、片岡嗣雄、岡橋暢夫、熊谷雄太郎、井上美津子、桑田啓貴
  • Organizer: 第９０回日本細菌学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2017-03-19
• [Presentation] インフルエンザウイルス感染は化膿レンサ球菌の上皮バリア突破を亢進させる (2017)
  • Author(s): 住友倫子、中田匡宣、山口雅也、川端重忠
  • Organizer: 第９０回日本細菌学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2017-03-19
• [Presentation] Streptococcus oralis 由来の過酸化水素はマクロファージのリソソームを傷害する (2016)
  • Author(s): 岡橋暢夫、中田匡宣、桑田啓貴、川端重忠
  • Organizer: 第５８回歯科基礎医学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-08-24
• [Presentation] インフルエンザウイルス感染に伴い上皮表層に誘導されるGP96は化膿レンサ球菌の上皮細胞への付着を亢進させる (2016)
  • Author(s): 住友倫子、中田匡宣、毛利泰士、小川真理子、山口雅也、川端重忠
  • Organizer: 第５８回歯科基礎医学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-08-24
• [Presentation] 環境温度の変化に対する肺炎球菌の適応と血中における菌体生存の関連 (2016)
  • Author(s): 中田匡宣、住友倫子、山口雅也、川端重忠
  • Organizer: 第５８回歯科基礎医学会学術大会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-08-24
• [Presentation] Streptococcus sanguinis 由来の過酸化水素は好中球に NETs を誘導する (2016)
  • Author(s): 住岡龍一、中田匡宣、和田聖史、岡橋暢夫、住友倫子、山口雅也、林美加子、川端重忠
  • 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（大阪府・大阪市）
  • Year and Date: 2016-03-23
• [Presentation] 培養温度の変化が肺炎球菌の血中での生存に及ぼす影響 (2016)
  • Author(s): 中田匡宣、住友倫子、山口雅也、川端重忠
  • 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（大阪府・大阪市）
  • Year and Date: 2016-03-23
• [Presentation] 口腔レンサ球菌が産生する過酸化水素は上皮細胞に対する細胞傷害性を有する (2015)
  • Author(s): 岡橋暢夫、中田匡宣、住友倫子、桜井敦朗、桑田啓貴、川端重忠
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県・新潟市）
  • Year and Date: 2015-09-11
• [Presentation] ミテイスレンサ球菌が産生する過酸化水素によるマクロファージ活性化制御 (2015)
  • Author(s): 松島瞳、片岡嗣雄、岡橋暢夫、井上美津子、桑田啓貴
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県・新潟市）
  • Year and Date: 2015-09-11
• [Presentation] Group A Streptococcus penetrates across an epithelial barrier via tricellular tight junctions. (2015)
  • Author(s): Sumitomo T, Nakata M, Yamaguchi M, Kawabata S
  • Organizer: 115th General Meeting of American Society for Microbiology
  • Place of Presentation: New Orleans (USA)
  • Year and Date: 2015-05-30
  • Int'l Joint Research
• [Presentation] Enzymatically active extracellular hyaluronidase (HylA) of group A Streptococcus promotes intracellular survival and virulence. (2014)
  • Author(s): Yamaguchi M, Yamaguchi Y, Nakata M, Henningham A, Olson J, Dahesh S, Cole J, Kawabata S, Varki A, Nizet V.
  • Organizer: SFG and JSCR 2014 Joint Annual Meeting
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2014-11-16 – 2014-11-19
• [Presentation] Role of Streptococcus sanguinis cell wall-anchored nuclease. (2014)
  • Author(s): Morita C, Nakata M, Sumioka R, Okahashi N, Hamada S, Sumitomo T, Kawabata S
  • Organizer: XIX Lancefield International Symposium on Streptococci and Streptococal Disease.
  • Place of Presentation: Buenos Aires, Argentina
  • Year and Date: 2014-11-09 – 2014-11-12
• [Presentation] 口腔レンサ球菌２型線毛の分布とその機能 (2014)
  • Author(s): 岡橋暢夫、中田匡宣、川端重忠
  • Organizer: 第５６回歯科基礎医学会学術大会
  • Place of Presentation: 福岡市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Streptococcus sanguinis の細胞壁架橋型ヌクレアーゼの酵素活性 (2014)
  • Author(s): 森田知里、住岡龍一、中田匡宣、和田聖史、岡橋暢夫、住友倫子、山口雅也、浜田茂幸、川端重忠
  • Organizer: 第５６回歯科基礎医学会学術大会
  • Place of Presentation: 福岡市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Book] 免疫系のしくみ (2015)
  • Author(s): 桑田啓貴、岡橋暢夫
  • Total Pages: 233
  • Publisher: 東京化学同人
• [Remarks] 大阪大学歯学研究科口腔科学フロンテイアセンターホームページ
  • URL: http://web.dent.osaka-u.ac.jp/~cfos/index.html
• [Remarks] 大阪大学歯学研究科口腔科学フロンテイアセンター
  • URL: http://web.dent.osaka-u.ac.jp/~cfos/index.html