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1998 Fiscal Year Final Research Report Summary

Molecular mechanisms for shigellae invasion of and spreading among colonic epithelial cells.

Research Project

Project/Area Number 09470074
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionThe University of Tokyo

Principal Investigator

SASAKAWA Chihiro  The University of Tokyo, Institute of med.Science, Professor, 医科学研究所, 教授 (70114494)

Co-Investigator(Kenkyū-buntansha) TOBE Toru  The University of Tokyo, Institute of med.Science, Lecturer, 医科学研究所, 講師 (70207596)
Project Period (FY) 1997 – 1998
KeywordsShigella / pathogenicity / invasiveness
Research Abstract

The project was aimed to investigate the molecular mechanisms of shigellae invasion and the subsequent spreading process within and among cells that is a critical step leading to shigellosis at early stage of infection of colonic epithelial cells by Shigella. In the study, the following findings are obtained.
Shigellae invasion : Ipa proteins secreted from shigellae play a crucial role in invasion of epithelial cells, since the Ipa proteins can interact with a5b1 integrin which promote bacterial invasion. The interaction was found to be involved in the activation of focal adhesion plaques, an even downstream of RhoA-regulated cellular signal, since C3 transferase can almost completely shut off the bacterial entry, while injection of Val l4RhoA, a constitutively activated form of RhoA protein, can promote bacterial internalization. The addition of Ipa proteins to the serum-starved fibroblast or epithelial cells can induce rapid rearrangement of actin cytoskeletons and condensation of maj … More or components of focal adhesion plaques. For the efficient shigellae invasion of epithelial cells, we noted another set of proteins including VirA secreted through Type-III system is crucial. Indeed, the expression of VirA or injection of GST-VirA fusions in mammalian cells can induce membrane ruffling. These results strongly indicate that shigellae invasion, a process resembling macropinocytosis, could be conducted by a cellular signal regulated by RhoA together with the induction of an additional signal possibly directed by the subset of shigellae proteins injected by the Type III system.
Shigellae spreading : Shigellae spreading within and among epithelial cells has been shown to be depended on the actin polymerization at one pole of bacterium in infected cells, that is mediated by shigellae VirG protein. In this study, we found that VirG can directly interact with two host factors, one is vinculin and the other is N-WASP, and the binding of the proteins under in vitro and in vivo conditions are mediated by the glycine-rich repeats domain of VirG.We also demonstrated that the bingeing of VirG to the two host proteins are functionally involved in the formation of actin tail form intracellular shigellae. Less

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Tobe,T.et al.: "A novel pathogenicity island of enteropathogenic E.coli(EPEC),with encodes a virulence-specific chaperone-like protein,EvcA,involved in micro colony-formation by EPEC." Mol.Micobiol.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okada,N.et al.: "Streptococcus pyogenes protein F promotes invasion of HeL a cells." Microbiology. 144. 3079-3086 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watarai,M.et al.: "Identification and characterization of a newly isolated Shigatoxin-converting phage from Shigatoxin-producing Escherichia coli." Infect.Immun.66. 4100-4107 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki,T.et al.: "Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri" EMBO J.17. 2767-2776 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Rajakumar, K.et al.: "Use of novel approach termed Island probingl identifies the Shigella she pathogenicty island encodes a homologue of the IgA protease-like family of proteins." Infect.Immun.65. 4606-4614 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Durand, J.et al.: "The modified nucleotide2-methylthio-N6-isopentenyladenosine in tRNA of Shigella flexneri is required for expression of virulence genes." J.Bacteriol.179. 5777-5782 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okada,N.at al: "A matrix form of fibronectin mediates enhanced binding of Streptococcus pyogenes to host tissue." J.Biol.Chem.272. 26978-26984 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakata,N.et al.: "Nucleotide sequence of the Mycobacterium leprae katG region." J.Bacteriol.179. 3053-3057 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watarai,M.et al.: "rho,a small GTP-binding protein, is essential for Shigella invasion of epithelial cells." J.Exp.Med.185. 281-292 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Rajakumar,K.et al.: "Identification of a chrom osomal Shigella flexneri multi-antibiotic resistance locus which shares sequence and organizational similarilty with" Plasmid.37. 159-168 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Rajakumar,K.et al.: "An evolutionary perspective on a composite Shigella flexneri 2a virulence plasmid-borne eomprising three genetic elements." FEMS Microbiol.Letter.144. 13-20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tobe, T., Tatsuno, I., Katayama, E., Wu, C-Y., Schoolnik, G.K., and Sasakawa, C.: "A novel pathogenicity island of enteropathogenic E.coli (EPEC) , which encodes a virulence-specific chaperone-like protein, EvcA,involved in microcolony-formation by EPEC." Mol.Micobiol.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okada, N., Tatsuno, I., Hanski, E., Caparon, M., and Sasakawa: "C.Streptococcus pyogenes protein F promotesinvation of HeLa cells." Microbiology. 144. 3079-3086 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watarai.M., Sato, T., Kobayashi, M., Shimizu, T., Yamasaki, S., Tobe, T., Sasakawa, C., and Takeda, Y.: "Identification and characterization of a newly isolated Shiga toxin-converting phage from Shiga toxin-producing Escherichia coli." Infect.Immun.66. 4100-4107 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki, T., Miki, H., Takenawa, T., and Sasakawa, C.: "Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri." EMBOJ.17. 2767-2776 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Rajakumar, K., Sasakawa, C., and Adler, B.: "Use of novel approach termed *island probing* identifies the Shigella she pathogenicty island encodes a homologue of the IgA protease-like family of proteins." Infect.Immun.65. 4606-4614 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Durand, J.M,B.Bjork, G.R., Kuwae, A., Yoshikawa, M.and Sasakawa, C.: "The modified nucleotide 2-methylthio-N6 isopentenyladenosine in tRNA of Shigella flexneri is required for expression of virulence genes." J.Bacteriol.179. 5777-5782 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okada, N.Watarai, M,Ozeri, V,Hanski, E,Caparon, and Sasakawa C.: "A matrix form of fibronectin mediates enhanced binding of Streptococcus pyogenes to host tissue." J.Biol.Chem.272. 26978-26984 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakata, N,Matsuoka, M,Kashiwabara, Y,Okada, N,Sasakawa, C.: "(1997) Nucleotide sequence of the Mycobacterium leprae katG region." J.Bacteriol.179. 3053-3057 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watari.M,Kamata Y,Kozaki S,and Sasakawa C.: "rho, a small GTP-binding protein, is essential for Shigella invasion of epithelial cells." J.Exp.Med.185. 281-292 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Rajakumar K.Lou F,Sasakawa C,and Adler B.: "Identification of a chromosomal Shigella flexneri multi-antibiotic resistance locus which shares sequence and orgaizational similarilty with the resistance region of the plasmid NR1." Plasmid.37. 159-168 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Rajakumar K.Lou F,Sasakawa C,and Adler B.: "An evolutionary perspective on a composite Shigella flexneri 2a virulence plasmid-borne eomprising three genetic elements." FEMS Microbiol.Letter.144. 13-20 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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