Real-time nanoscale analysis of immune evasion molecules from Streptococcus pyogenes using bio-imaging technologies

• Project/Area Number: 21689048
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Morphological basic dentistry
• Research Institution: Osaka University
• Principal Investigator: TERAO Yutaka Osaka University, 大学院・歯学研究科, 准教授 (50397717)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000); Fiscal Year 2010: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2009: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
• Keywords: 感染症 / 細菌 / 微生物 / 免疫学 / バイオ関連機器 / バイオ関連機

Research Abstract

Neutrophils are part of the initial group of immune cells recruited to the site of infection. However, in severe streptococcal infection including streptococcal toxic shock syndrome, few neutrophils have been found near Streptococcus pyogenes, which rapidly infects various organs in STSS patients. S.pyogenes is thought to be equipped with virulence factors to evade the neutrophil immune system. Previously, we found that complement C3b functioned as an opsonin is degraded in sera from patients with streptococcal toxic shock syndrome. Furthermore, it has been revealed that S.pyogenes is able to fragment neutrophil extracellular traps (NETs). In the present study, we investigated the mechanism of S.pyogenes evasion from neutrophils. Biacore analysis demonstrated that rSpeB and wild-type S.pyogenes rapidly degrade C3b. In a mouse model, bacterial survival rate was lower for the ΔspeB mutant than the wild-type strain. Furthermore, histopathological observations showed that neutrophils infiltrated to the site of infection by the ΔspeB mutant, whereas few migrated to the infection site in mice injected with the wild type and S. pyogenes continued to spread along the fascia. Time-lapse microscopic analysis revealed that digestion of NETs was seen by the wild-type strain, but not ΔspeB mutant strain. Our results indicate that SpeB contributes to the escape of S. pyogenes from neutrophil immunity by degrading C3b and NETs at the site of initial infection.

Research Products

• [Journal Article] Biofilm formation or internalization into epithelial cells enable Streptococcus pyogenes to evade antibiotic eradication in patients with pharyngitis. (2011)
  • Author(s): Ogawa, T., Terao, Y., Okuni, H., Ninomiya, K., Sakata, H., Ikebe, K., Maeda, Y., Kawabata, S.
  • Journal Title: Microb. Pathog. (in press,出版予定)
  • Peer Reviewed
• [Journal Article] Epidemiological characterization of Streptococcus pyogenes isolated from patients with multiple onsets of pharyngitis. (2011)
  • Author(s): Ogawa, T., Terao, Y., Sakata, H., Okuni, H., Ninomiya, K., Ikebe, K., Maeda, Y., Kawabata, S.
  • Journal Title: FEMS Microbiol.Lett. 318 Pages: 143-151
  • Peer Reviewed
• [Journal Article] Pili of oral Streptococcus sanguinis bind to salivary amylase and promote the biofilm formation. (2011)
  • Author(s): Okahashi, N., Nakata M., Sakurai A., Terao Y., Hoshino T., Yamaguchi Y., Isoda R., Sumitomo T., Nakano K., Kawabata S., Ooshima T.
  • Journal Title: Microb. Pathog. 50 Pages: 148-154
  • Peer Reviewed
• [Journal Article] Streptolysin S contributes to group A streptococcal translocation across an epithelial barrier. (2011)
  • Author(s): Sumitomo, T., Nakata M., Higashino M., Jin Y., Terao Y., Fujinaga Y., Kawabata S.
  • Journal Title: J.Biol.Chem. 286 Pages: 2750-2761
  • Peer Reviewed
• [Journal Article] Streptolysin S contributes to group A streptococcal translocation across an epithelial barrier (2011)
  • Author(s): Sumitomo, T., Nakata M., Higashino M., Jin Y., Terao Y., Fujinaga Y., Kawabata S.
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 2750-2761
  • Peer Reviewed
• [Journal Article] Pili of oral Streptococcus sanguinis bind to salivary amylase and promote the biofilm formation (2011)
  • Author(s): Okahashi, N., Nakata M., Sakurai A., Terao Y., Hoshino T., Yamaguchi Y., Isoda R., Sumitomo T., Nakano K., Kawabata S., Ooshima T.
  • Journal Title: Microbial Pathogenesis Volume: 50 Pages: 148-154
  • Peer Reviewed
• [Journal Article] Epidemiological characterization of Streptococcus pyogenes isolated from patients with multiple onsets of pharyngitis (2011)
  • Author(s): Ogawa, T., Terao, Y., Sakata, H., Okuni, H., Ninomiya, K., Ikebe, K., Maeda, Y., Kawabata S.
  • Journal Title: FEMS Microbiology Letters Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Biofilm formation or internalization into epithelial cells enable Streptococcus pyogenes to evade antibiotic eradication in patients with pharyngitis (2011)
  • Author(s): Ogawa, T., Terao, Y., Okuni, H., Ninomiya, K., Sakata, H., Ikebe, K., Maeda, Y., Kawabata S.
  • Journal Title: Microbial Pathogenesis Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Fusobacterium nucleatum envelope protein, FomA, is immunogenic and binds to salivary statherin-derived peptide. (2010)
  • Author(s): Nakagaki, H., Sekine S., Terao Y., Toe M., Tanaka M., Shizukuishi S., Ito H., Kawabata S., McGhee JR., Fujihashi K., Kataoka K.
  • Journal Title: Infect. Immun. 78 Pages: 1185-1192
  • Peer Reviewed
• [Journal Article] Pili of oral Streptococcus sanguinis bind to fibronectin and contribute to cell adhesion. Biochem. (2010)
  • Author(s): Okahashi, N., Nakata M., Sakurai A., Terao Y., Hoshino T., Yamaguchi Y., Isoda R., Sumitomo T., Nakano K., Kawabata S., Ooshima T.
  • Journal Title: Biophys.Res.Commun. 391 Pages: 1192-1196
  • Peer Reviewed
• [Journal Article] Fusobacterium nucleatum envelope protein FomA is immunogenic and binds to the salivary statherin-derived peptide (2010)
  • Author(s): Nakagaki, H., Sekine S., Terao Y., Toe M., Tanaka M., Shizukuishi S., Ito H., Kawabata S., McGhee JR., Fujihashi K., Kataoka K.
  • Journal Title: Infection and Immunity Volume: 78 Pages: 1185-1192
  • Peer Reviewed
• [Journal Article] Pili of oral Streptococcus sanguinis bind to fibronectin and contribute to cell adhesion. (2010)
  • Author(s): Okahashi N, M.Nakata, A.Sakurai, Y.Terao, T.Hoshino, M.Yamaguchi, R.Isoda, T.Sumitomo, K.Nakano, S.Kawabata, T.Ooshima.
  • Journal Title: Biochem.Biophys.Res.Commun. 391(2) Pages: 1192-1196
  • Peer Reviewed
• [Journal Article] Nrc of Streptococcus pneumoniae suppresses capsule expression and enhances anti-phagocytosis. Biochem. (2009)
  • Author(s): Yamaguchi, M., Minamide M., Terao Y., Isoda R., Ogawa T., Yokota S., Hamada S.Kawabata S.
  • Journal Title: Biophys.Res.Commun. 390 Pages: 155-160
  • Peer Reviewed
• [Journal Article] Molecular and biological characterization of novel gtf regulation-associated genes in Streptococcus mutans. (2009)
  • Author(s): Terao, Y., Isoda R., Murakami, J.Hamada, S.Kawabata, S.
  • Journal Title: Oral Microbiol. Immunol. 24 Pages: 211-217
  • Peer Reviewed
• [Journal Article] Mode of expression and functional characterization of FCT-3 pilus region encoded proteins in the Streptococcus pyogenes serotype M49. (2009)
  • Author(s): Nakata, M., Koller, T., Moritz, K., Ribardo, D., Jonas, L., McIver, K.S., Sumitomo, T., Terao, Y., Kawabata, S., Podbielski, A.Kreikemeyer, B.
  • Journal Title: Infect. Immun. 77 Pages: 32-44
  • Peer Reviewed
• [Journal Article] Nrc of Streptococcus pneumoniae suppresses capsule expression and enhances anti-phagocytosis. (2009)
  • Author(s): Yamaguchi, M., Y.Minaimide, Y.Terao, R.Isoda, T.Ogawa, S.Yokota, S.Hamada, S.Kawabata.
  • Journal Title: Biochem.Biophys.Res.Commun. 390(1) Pages: 155-160
  • Peer Reviewed
• [Journal Article] Molecular and biological characterization of novel gtf regulation-associated genes in Streptococcus mulans. (2009)
  • Author(s): Terao, Y., R.Isoda, J.Murakami, S.Hamada, S.Kawabata.
  • Journal Title: Oral Microbiol.Immunol. 24(3) Pages: 211-217
  • Peer Reviewed
• [Journal Article] Mode of expression and functional characterization of FCT-3 piles region encoded proteins in the Streptococcus pyogenes serotype M49. (2009)
  • Author(s): Nakata, M., T.Kuller, K.Moritz, D.Ribardo, L.Jonas, K.S.McIver, T.Sumitomo, Y.Terao, S.Kawabata, A.Podbielski, B.Kreikemeyer.
  • Journal Title: Infect.Immun. 77(1) Pages: 32-44
  • Peer Reviewed
• [Presentation] M6型A群レンサ球菌が産生する線毛形成機構と機能解析 (2010)
  • Author(s): 木村敬次リチャード, 住友倫子, 寺尾豊, 磯田竜太朗, 中田匡宣, 川端重忠
  • Organizer: 第63回日本細菌学会関西支部総会
  • Place of Presentation: 枚方市
  • Year and Date: 2010-11-20
• [Presentation] Streptolysin S contributes to group A streptococcal paracellular translocation across epithelial cells. (2010)
  • Author(s): Sumitomo T, Nakata M, Terao Y, Kawabata S.
  • Organizer: The 10th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji, Hyogo, Japan.
• [Presentation] Characterization of Streptococcus pyogenes isolated from patients with recurrent pharyngitis. (2010)
  • Author(s): Ogawa T, Terao Y, Ohkuni H, Ninomiya K, Sakata H, Ikebe K, Maeda Y, Kawabata S.
  • Organizer: 88^<th> General Session & Exhibition of the International Association for Dental Research.
  • Place of Presentation: Barcelona, Spain.
• [Presentation] Streptococcus pneumoniae evades neutrophil phagocytosis through its surface protein PfbA. (2010)
  • Author(s): Yamaguchi M, Terao Y, Nishino K, Yamaguchi A, Hamada S, Kawabata, S.
  • Organizer: 110th General Meeting of American Society for Microbiology.
  • Place of Presentation: San Diego, USA.
• [Presentation] Streptolysin S contributes to group A streptococcal paracellular translocation across epithelial cells (2010)
  • Author(s): T.Sumitomo, M.Nakata, Y.Terao, S.Kawabata
  • Organizer: 第62回日本細胞生物学会
  • Place of Presentation: 大阪市
• [Presentation] Streptococcus pneumoniae evades neutrophil phagocytosis through its surface protein PfbA (2010)
  • Author(s): M.Yamaguchi, Y.Terao, K.Nishino, A.Yamaguchi, S.Hamada, S.Kawabata
  • Organizer: 110^<th> General Meeting of the American Society for Microbiology
  • Place of Presentation: San Diego CA, U.S.A.
• [Presentation] 再発性咽頭炎患者より分離されたA群レンサ球菌の分子解析に基づく新規治療法の提案 (2010)
  • Author(s): 小川泰治, 寺尾豊, 大国壽士, 二宮恵子, 坂田宏, 入江正寛, 本間信夫, 中野正大, 明貝路子, 浜田茂幸, 川端重忠
  • Organizer: 第19回レンサ球菌研究会
  • Place of Presentation: 東京都
• [Presentation] Characterization of Streptococcus pyogenes Isolated from Patients with Recurrent Pharyngitis (2010)
  • Author(s): T.Ogawa., Y.Terao, H.Ohkuni, K.Ninomiya, H.Sakata, K.Ikebe, Y.Maeda, S.Kawabata
  • Organizer: 88^<th> General Session and Exhibition of the IADR
  • Place of Presentation: Barcelona, Spain
• [Presentation] Streptococcus pyogenes C6結合タンパクのナノスケール・バイオイメージング解析 (2010)
  • Author(s): 寺尾豊, 浜田茂幸, 川端重忠
  • Organizer: 第47回補体シンポジウム
  • Place of Presentation: 福島市
• [Presentation] 病態観察とゲノム情報から展開するA群レンサ球菌の分子解析 (2010)
  • Author(s): 寺尾豊, 川端重忠
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京都(招待講演)
• [Presentation] Streptolysin S contributes to group A streptococcal paracellular translocation across epithelial cells (2010)
  • Author(s): T.Sumitomo, M.Nakata, Y.Terao, S.Kawabata
  • Organizer: 10^<th> Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji, Japan
• [Presentation] Streptococcus pneumoniaeは赤血球に侵入し自然免疫を回避する (2010)
  • Author(s): 山口雅也, 寺尾豊, 八木哲也, 西野邦彦, 山口明人, 川端重忠
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸市
• [Presentation] 新規免疫システムNETsを誘導する肺炎レンサ球菌タンパクの同定 (2010)
  • Author(s): 森有可, 寺尾豊, 山口雅也, 浜田茂幸, 大嶋隆, 川端重忠
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸市
• [Presentation] 難治性咽頭炎の発症メカニズム解析と再発防止へのアプローチ (2010)
  • Author(s): 小川泰治, 寺尾豊, 坂田宏, 川端重忠
  • Organizer: 第80回日本感染症学会 西日本地方会学術集会
  • Place of Presentation: 松山市
• [Presentation] A群レンサ球菌の上皮バリア突破機構に関与する宿主プロテアーゼの検索 (2010)
  • Author(s): 住友倫子, 中田匡宣, 東野美晴, 寺尾豊, 川端重忠
  • Organizer: 第7回感染症沖縄フォーラム
  • Place of Presentation: 那覇市
• [Presentation] Streptococcus pyogenesの補体C6結合タンパクの同定と機能解析 (2010)
  • Author(s): 寺尾豊, 浜田茂幸, 川端重忠
  • Organizer: 第83回日本細菌学会総大会
  • Place of Presentation: 横浜市
• [Presentation] A群レンサ球菌が産生する線毛の細胞壁架橋機構の解析 (2010)
  • Author(s): 中田匡宣, 住友倫子, 磯田竜太朗, 寺尾豊, 川端重忠
  • Organizer: 第83回日本細菌学会総大会
  • Place of Presentation: 横浜市
• [Presentation] A群レンサ球菌の上皮バリア突破機構に関与する宿主プロテアーゼの解析 (2010)
  • Author(s): 住友倫子, 中田匡宣, 東野美晴, 寺尾豊, 川端重忠
  • Organizer: 第83回日本細菌学会総大会
  • Place of Presentation: 横浜市
• [Presentation] Streptococcus pneumoniaeと赤血球の相互作用の解祈 (2010)
  • Author(s): 山口雅也, 寺尾豊, 川端重忠
  • Organizer: 第83回日本細菌学会総大会
  • Place of Presentation: 横浜市
• [Presentation] Streptococcus pneumoniaeの自然免疫回避におけるEnolaseの役割 (2010)
  • Author(s): 森有可, 寺尾豊, 山口雅也, 浜田茂幸, 川端重忠
  • Organizer: 第83回日本細菌学会総大会
  • Place of Presentation: 横浜市
• [Presentation] A群レンサ球菌性咽頭炎の再発メカニズムの解祈 (2010)
  • Author(s): 小川泰治, 寺尾豊, 大國壽士, 二宮恵子, 坂田宏, 川端重忠
  • Organizer: 第83回日本細菌学会総大会
  • Place of Presentation: 横浜市
• [Presentation] 宿主細胞間接着分子の破壊に関与するA群レンサ球菌プロテアーゼの検索 (2010)
  • Author(s): 東野美晴, 住友倫子, 中田匡宣, 寺尾豊, 川端重忠
  • Organizer: 第83回日本細菌学会総大会
  • Place of Presentation: 横浜市
• [Presentation] Streptococcus pneumoniaeの好中球に対する抗食食能のバイオイメージング解析 (2009)
  • Author(s): 山口雅也, 寺尾豊, 浜田茂幸, 川端重忠
  • Organizer: 第62回日本細菌学会関西支部総会
  • Place of Presentation: 泉佐野市
  • Year and Date: 2009-11-04
• [Presentation] Neonatal exposure induced commensal-like immune-response against Aggregatibacter actinomycetemcomitans in mice. (2009)
  • Author(s): Isoda R, Terao Y, Nakata M, Sumitomo T, Kawabata S.
  • Organizer: 87th General Session & Exhibition of the International Association for Dental Research.
  • Place of Presentation: Miami, USA.
• [Presentation] FomA specific-salivary secretary-IgA inhibits Fusobacterium nucleatum binding to statherin. (2009)
  • Author(s): Kataoka K, Nakagaki H, Terao Y, Toe M, Sekine S, Fujihashi K, Kawabata S, Shizukuishi S.
  • Organizer: 87th General Session & Exhibition of the International Association for Dental Research.
  • Place of Presentation: Miami, USA.
• [Presentation] Group A Streptococci translocates across epithelial barrier via intercellular junction cleavage. (2009)
  • Author(s): Sumitomo T, Nakata M, Terao Y, Kawabata S.
  • Organizer: 109th General Meeting of American Society for Microbiology.
  • Place of Presentation: Philadelphia, USA.
• [Presentation] Cysteine protease SpeB enables Streptococcus pyogenes to evade neutrophil immunity. (2009)
  • Author(s): Terao Y, Yamaguchi M, Ogawa T, Kawabata S.
  • Organizer: FEMS 2009 3rd Congress of European Microbiologists.
  • Place of Presentation: Gothenburg, Sweden
• [Presentation] Role of Streptococcus pneumoniae PfbA in adhesion to human epithelial cells and resistance to neutrophil phagocytosis. (2009)
  • Author(s): Yamaguchi M, Terao Y, Hamada S, Kawabata S.
  • Organizer: The 9th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji, Hyogo, Japan.
• [Presentation] Group A streptococci translocates across epithelial barrier via intercellular junction cleavage (2009)
  • Author(s): Sumitomo T., M.Nakata, Y.Terao, S.Kawabata.
  • Organizer: 109^<th> General Meeting American Society for Microbiology
  • Place of Presentation: Philadelphia, U.S.A.
• [Presentation] Cysteine protease SpeB enables Streptococcus pyogenes to evade neutrophil immunity (2009)
  • Author(s): Terao Y, M.Yamaguchi, T.Ogawa, S.Kawabata.
  • Organizer: 3^<rd> FEMS Congress of European Microbiologists
  • Place of Presentation: Gotenburg, Sweden
• [Presentation] Role of Streptococcus pneumoniae PfbA in adhesion to human epithelial cells and resistance to neutrophil phagocytosis (2009)
  • Author(s): Yamaguchi M., Y.Terao, S.Hamada, S.Kawabata
  • Organizer: 9^<th> Awaji International Forum on Infection and Immunity
  • Place of Presentation: Hyogo, Japan
• [Presentation] 菌体表層クンパクPfbAによるStreptococcus pneumoniaeの上皮細胞定着と抗食機構のバイオイメージング解析 (2009)
  • Author(s): 山口雅也, 寺尾豊, 森有可, 浜田茂幸, 川端重忠
  • Organizer: 第18回Lancefieldレンサ球菌研究会
  • Place of Presentation: 福岡市
• [Presentation] 再発性咽頭炎患者より分離されたA群レンサ球菌の分子生物学的解析 (2009)
  • Author(s): 小川泰治, 孝尾豊, 大国壽士, 二宮恵子, 浜田茂幸, 川端重忠
  • Organizer: 第18回Lancefieldレンサ球菌研究会
  • Place of Presentation: 福岡市
• [Presentation] 口腔領城レンサ球菌による宿主上皮細胞への付着侵入と炎症の誘導 (2009)
  • Author(s): 桜井敦朗, 岡橋暢夫, 中田匡宣, 寺尾豊, 丸山史人, 川端重忠, 大嶋隆
  • Organizer: 第18回Lancefieldレンサ球菌研究会
  • Place of Presentation: 福岡市
• [Presentation] A群レンサ球菌が産生する線毛の発現機構の解析 (2009)
  • Author(s): 中田匡宣, 寺尾豊, 川端重忠
  • Organizer: 第51回日本歯科基礎医学会
  • Place of Presentation: 新潟市
• [Presentation] ターメリックはStreptococcus mutansの生育を阻害する (2009)
  • Author(s): 泉井秀介, 山口雅也, 寺尾豊, 川端重忠
  • Organizer: 第51回日本歯科基礎医学会
  • Place of Presentation: 新潟市
• [Book] 口腔微生物学・免疫学第三版(浜田茂幸, 川端重忠, 西原達次, 菅井基行, 中川一路編) (2010)
  • Author(s): 寺尾豊, 川端重忠
  • Publisher: 医歯薬出版社
• [Book] 口腔微生物学・免疫学第3版 (2010)
  • Author(s): 寺尾豊, 川端重忠(浜田茂幸, 川端重忠, ら編)
  • Total Pages: 279
  • Publisher: 医歯薬出版社
• [Book] A群レンサ球菌のサバイバル・ストラテジー,蛋白質核酸酵素増刊号,54 (2009)
  • Author(s): 寺尾豊, 川端重忠
  • Publisher: 共立出版
• [Book] -感染現象 その理解の深化から疾患制御への展望-蛋白質核酸酵素2009年6月増刊号担当頁「A群連鎖球菌のサバイバル・ストラテジー」 (2009)
  • Author(s): 寺尾豊, 川端重忠(木下タロウ, 熊ノ郷淳, 竹田潔, 松浦善治, 川端重忠(編))
  • Publisher: 共立出版
• [Remarks] ホームページ等
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• [Remarks]
  • URL: http://www.dent.osaka-u.ac.jp/admission/course/mcrbio.html
• [Remarks]
  • URL: http://www.dent.osaka-u.ac.jp/~mcrbio/kenkyuu.html