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

2010 Fiscal Year Final Research Report

• 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
• Keywords: 感染症 / 細菌 / 微生物 / 免疫学 / バイオ関連機器

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] 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] 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
• [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.
  • Year and Date: 20100907-20100910
• [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.
  • Year and Date: 20100714-20100717
• [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.
  • Year and Date: 20100523-20100527
• [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.
  • Year and Date: 20090908-20090911
• [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
  • Year and Date: 20090628-20090702
• [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.
  • Year and Date: 20090517-20090521
• [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.
  • Year and Date: 20090401-20090404
• [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.
  • Year and Date: 20090401-20090404
• [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
  • Total Pages: 89-92
  • 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
  • Total Pages: 982-987
  • Publisher: 共立出版
• [Remarks] ホームページ等
  • URL: http://web.dent.osaka-u.ac.jp/~mcrbio/kenkyuuterao1.html