Molecular analysis of bacterial invasion strategies and intracellular growth of pathogenic streptococci

2010 Fiscal Year Final Research Report

• Project Area: Matrix of Infection Phenomena
• Project/Area Number: 18073011
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: KAWABATA Shigetada Osaka University, 大学院・歯学研究科, 教授 (50273694)
• Co-Investigator(Kenkyū-buntansha): TERAO Yutaka 大阪大学, 大学院・歯学研究科, 准教授 (50397717) ; NAKATA Masanobu 大阪大学, 大学院・歯学研究科, 助教 (90444497)
• Project Period (FY): 2006 – 2010
• Keywords: レンサ球菌 / 組織侵入 / 増殖 / タンパク質 / 病原因子 / 感染症 / 細菌 / 微生物

Research Abstract

Streptococcus pyogenes causes pharyngitis, sepsis, and rheumatic fever. Cell-associated streptococcal C5a peptidase (ScpA) protects S. pyogenes from phagocytosis and has been suggested to interrupt host defenses by enzymatically cleaving complement C5a, a major factor in the accumulation of neutrophils at sites of infection. How S. pyogenes recognizes and binds to C5a, however, is unclear. We detected a C5a-binding protein in 8 M urea extracts of S. pyogenes by ligand blotting using biotinylated C5a. Searching of genome databases showed that the C5a-binding protein is identical to the streptococcal plasmin receptor (Plr), also known as streptococcal surface dehydrogenase (SDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the present study, we identified a novel function of this multifunctional protein. We examined whether the streptococcal Plr/SDH/GAPDH inhibits the biological effects of C5a on human neutrophils. Together, these results indicate that the multifunctional protein Plr/SDH/GAPDH has additional functions that help S. pyogenes escape detection by the host immune system.

Research Products

• [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(4) 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(3) 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., Nakata M., Sakurai A., Terao Y., Hoshino T., Yamaguchi Y., Isoda R., Sumitomo T., Nakano K., Kawabata S., Ooshima T.
  • Journal Title: Biochem. 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(1) 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] PfbA, a Novel Plasmin-and Fibronectin-binding Protein of Streptococcus pneumoniae Contributes to Fibronectin-dependent Adhesion and Antiphagocytosis. (2008)
  • Author(s): Yamaguchi, M., Terao, Y., Hamada, S.Kawabata, S.
  • Journal Title: J.Biol.Chem. 283 Pages: 36272-36279
  • Peer Reviewed
• [Journal Article] A novel streptococcal leucine zipper protein (Lzp) that binds to binds to human immunoglobulins. (2008)
  • Author(s): Okamoto, S., Terao, Y., Hasuike, K., Hamada, S.Kawabata, S.
  • Journal Title: Biochem. Biophys.Res.Commun. 377 Pages: 1128-1134
  • Peer Reviewed
• [Journal Article] Group A streptococcal cysteine protease degrades C3 (C3b) and contributes to evasion of innate immunity. (2008)
  • Author(s): Terao, Y., Mori, Y., Yamaguchi, M., Shimizu, Y., Ooe, K., Hamada, S.Kawabata S.
  • Journal Title: J.Biol.Chem. 283 Pages: 6253-6260
  • Peer Reviewed
• [Journal Article] Molecular and biological characterization of histidine triad protein in group A streptococci. (2008)
  • Author(s): Kunitomo, E., Terao, Y., Okamoto, S., Rikimaru, T., Hamada, S.Kawabata, S.
  • Journal Title: Microbes Infect. 10 Pages: 414-423
  • Peer Reviewed
• [Journal Article] Streptococcal immunoglobulin-binding protein Sib35 exerts stimulatory and mitogenic effects toward mouse B lymphocytes. (2008)
  • Author(s): Okamoto, S., Terao, Y., Tamura, Y., Hamada, S.Kawabata, S.
  • Journal Title: FEMS Microbiol.Lett. 281 Pages: 73-80
  • Peer Reviewed
• [Journal Article] Molecular cloning of novel Monad binding protein containing tetratricopeptide repeat domains. (2008)
  • Author(s): Itsuki ,Y., Saeki, M., Nakahara, H., Egusa, H., Irie, Y., Terao, Y., Kawabata, S., Yatani, H.Kamisaki, H.
  • Journal Title: FEBS Lett. 582 Pages: 2365-2370
  • Peer Reviewed
• [Journal Article] Calcineurin potentiates the activation of procaspase-3 by accelerating its proteolytic maturation. (2007)
  • Author(s): Saeki, M., Irie, Y.Ni, L.Itsuki, Y.Terao, Y., Kawabata, S.Kamisaki Y.
  • Journal Title: J.Biol.Chem., 282 Pages: 11786-11794
  • Peer Reviewed
• [Journal Article] Induction of immune responses by streptococcal water-insoluble alpha-glucans. (2007)
  • Author(s): Okamaoto, S., Terao, Y., Kaminishi, H., Hamada, S.Kawabata S.
  • Journal Title: J.Dent.Res. 86 Pages: 242-248
  • Peer Reviewed
• [Journal Article] Role of Streptococcus sanguinis sortase A in bacterial colonization. (2006)
  • Author(s): Yamaguchi, M., Terao, Y., Ogawa, T., Takahashi, T., Hamada, S.Kawabata S.
  • Journal Title: Microbes Infect. 8 Pages: 2791-2796
  • Peer Reviewed
• [Journal Article] Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils. (2006)
  • Author(s): Terao, Y., Yamaguchi, M., Hamada, S.Kawabata, S.
  • Journal Title: J.Biol.Chem. 281 Pages: 14215-14223
  • Peer Reviewed
• [Journal Article] Biofilm formation or internalization into epithelial cells enable Streptococcus pyogenes to evade antibiotic eradication in patients with pharyngitis.
  • Author(s): Ogawa, T., Terao, Y., Okuni, H., Ninomiya, K., Sakata, H., Ikebe, K., Maeda, Y., Kawabata, S.
  • Journal Title: Microb. Pathog. 2011(in press,出版予定)
  • 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] Nasal cholera toxin activated mucosal dendritic cells, but not CD4+ T cells elicit TI-IgG class switching recombinationby B-1 B cells. (2010)
  • Author(s): Kataoka K, Fujihashi K, Kobayashi R, Gilbert RS, Sekine S, Fukui M, Fukuyama Y, Kawabata S, Ito H, Fujihashi K.
  • Organizer: 14th International Congress on Immunology.
  • Place of Presentation: Kobe Hyogo, Japan.
  • Year and Date: 20100822-20100827
• [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] Anticariogenic effects of Oenothera biennis seed extracts on Streptococcus mutans activity. (2010)
  • Author(s): Matsumoto-Nakano M, Nagayama K, Fujita K, Inagaki S, Takashima Y, Kawabata S, Ooshima T.
  • Organizer: The 57th congress of the European Organization for Caries Research.
  • Place of Presentation: Montpellier, France
  • Year and Date: 20100707-20100710
• [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
• [Presentation] Streptococcus pyogenes degrades complements C3 and C3b to evade of innate immune system. (2008)
  • Author(s): Terao Y, Mori Y, Yamaguchi M, Hamada S, Kawabata S.
  • Organizer: The 8^<th> Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Higashiura, Hyogo, Japan.
  • Year and Date: 20080907-20080911
• [Presentation] Impact of novel multi-functional protein PfbA on adherence, invasion, and antiphagocytosis by Streptococcus pneumoniae. (2008)
  • Author(s): Yamaguchi M, Terao Y, Mori Y, Hamada S, Kawabata S.
  • Organizer: The International Union of Microbiological Societies 2008.
  • Place of Presentation: Istanbul, Turkey.
  • Year and Date: 20080805-20080809
• [Presentation] Role of the Streptococcus pyogenes serotype M49 FCT-3 region encoded pilus in virulence. (2008)
  • Author(s): Nakata M, Koller T, McIver KS, Kawabata S, Podbielski A, Kreikemeyer B.
  • Organizer: 17^<th> Lancefield International Symposium on Streptococci and Streptococcal Diseases.
  • Place of Presentation: Porto Heli, Greece.
  • Year and Date: 20080622-20080626
• [Presentation] Group A streptococcal cysteine protease degrades complement C3 and contributes to evasion of innate immunity in severe streptococcal infections. (2008)
  • Author(s): Terao Y, Mori Y, Yamaguchi M, Hamada S, Kawabata S.
  • Organizer: 108^<th> General Meeting of American Society for Microbiology.
  • Place of Presentation: Boston, USA.
  • Year and Date: 20080601-20080605
• [Presentation] Role of the Streptococcus pyogenes FCT-region components in pilus assembly and virulence. (2007)
  • Author(s): Nakata M, Ribardo DA, McIver KS, Podbielski A, Kreikemeyer B, Kawabata S.
  • Organizer: The ^<7th> Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Higashiura, Hyogo, Japan.
  • Year and Date: 20070901-20070905
• [Presentation] Plasmin(ogen)-and fibronectin-binding protein of Streptococcus pneumoniae provides bacterial plasmin activity. (2007)
  • Author(s): Yamaguchi M, Terao Y, Mori Y, Hamada S, Kawabata S.
  • Organizer: 107^<th> General Meeting of American Society for Microbiology.
  • Place of Presentation: Toronto, Canada.
  • Year and Date: 20070521-20070525
• [Presentation] Role of Streptococcus pyogenes FCT-region sortase and other components in pilus assembly and virulence. (2007)
  • Author(s): Nakata M, Ribardo DA, McIver KS, Kawabata S, Podbielski A, Kreikemeyer B.
  • Organizer: 107th General Meeting of American Society for Microbiology.
  • Place of Presentation: Toronto, Canada.
  • Year and Date: 20070521-20070525
• [Presentation] Inflammatory immune responses by water-insoluble alpha-glucans from Streptococcus sobrinus. (2007)
  • Author(s): Okamoto S, Terao Y, Kaminishi H, Hamada S, Kawabata S.
  • Organizer: The 2^<nd> International Symposium for Interface Oral Health Science.
  • Place of Presentation: Sendai, Miyagi, Japan.
  • Year and Date: 20070218-20070219
• [Presentation] Streptococcus mutans clonal variation revealed by multilocus sequence typing. (2007)
  • Author(s): Lapirattanakul J, Nakano K, Kawabata S, Ooshima T.
  • Organizer: The 2^<nd> Thailand-Japan Joint Forum on Infectious Diseases.
  • Place of Presentation: Bangkok, Thailand.
  • Year and Date: 2007-10-08
• [Presentation] Identification of a novel plasmin (ogen)- and fibronectin-binding protein in Streptococcus pneumoniae. (2006)
  • Author(s): Yamaguchi M, Terao Y, Mori Y, Hamada S, Kawabata S.
  • Organizer: The 46^<th> Interscience Conference on Antimicrobial Agents and Chemotherapy.
  • Place of Presentation: San Francisco, CA, USA.
  • Year and Date: 20060927-20060930
• [Presentation] Multifunctional glyceralaldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils. (2006)
  • Author(s): Kawabata S, Terao Y, Hamada S.
  • Organizer: The 2^<nd> FEMS Congress of European Microbiologist.
  • Place of Presentation: Madrid, Spain.
  • Year and Date: 20060704-20060708
• [Book] 口腔微生物学・免疫学第三版 (2010)
  • Author(s): 浜田茂幸, 川端重忠, 西原達次, 菅井基行, 中川一路編
  • 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
  • Total Pages: 982-987
  • Publisher: 共立出版
• [Book] 病原性レンサ球菌の病原因子の機能解析.生命歯科医学のカッティング・エッジ(米田俊之編) (2008)
  • Author(s): 寺尾豊, 住友倫子, 中田匡宣, 磯田竜太朗, 川端重忠
  • Total Pages: 68-78
  • Publisher: 大阪大学出版会
• [Remarks] ホームページ等
  • URL: http://web.dent.osaka-u.ac.jp/~mcrbio/