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MOLECULAR MECHANISM OF VIRULENT FACTOR PRODUCTION IN GRAM POSITIVE BACTERIA

Research Project

Project/Area Number 08407010
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionUniversity of Tsukuba

Principal Investigator

HAYASHI Hideo  INSTITUTE OF BASIC MEDICAL SCIENCES, UNIVERSITY OF TSUKUBA, PROFESSOR, 基礎医学系, 教授 (40033203)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Tohru  INSTITUTE OF BASIC MEDICAL SCIENCES, UNIVERSITY OF TSUKUBA, ASSOCIATE PROFESSOR, 基礎医学系, 助教授 (80235655)
OHTA Toshiko  MEDICAL TECHNOLOGY, UNIVERSITY OF TSUKUBA, PROFESSOR, 医療短期大学, 教授 (40233134)
NAKAMURA Shinichi  DEPARTMENT OF MICROBIOLOGY, KANAZAWA UNIVERSITY, PROFESSOR, 医学部, 教授 (90019620)
KURAZONO Hisao  HEALTH SCIENCES, OKAYAMA UNIVERSITY, PROFESSOR, 医学部, 教授 (90186487)
Project Period (FY) 1996 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥36,500,000 (Direct Cost: ¥36,500,000)
Fiscal Year 1999: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1998: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1997: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1996: ¥11,500,000 (Direct Cost: ¥11,500,000)
KeywordsGram Positive bacteria / Stress response mechanism / Heat shock / Transcription factors / Staphylococcus aureus / Clostridium / Antibiotics / 抗菌剤 / 環境適応 / クロストリジュウム / ディフィシル菌 / 黄色ブドウ球菌 / ウェルシュ菌 / 毒素 / ストレス応答 / 遺伝子発現調節 / 細胞内情報伝達 / 熱ショック蛋白 / ウエルシュ菌 / 原子力問顕微鏡 / 転写調節 / 溶血毒素 / 調節遺伝子
Research Abstract

Molecular mechanism of production of toxins and the other virulence factors in Gram positive bacteria has been investigated to develop novel infection control measures for Gram positive bacteria which produce variety of virulence factors to cause desease in human.
1. The production of toxins and enzymes was regulated by the environmental factors.
The production of toxins (α, β, γ, ε, θ, etc, in Clostridium perfringens, toxin A and B in C. difficile, soluble and surface virulent factors in Staphylococcus aureus) was regulated by the growth phase, density/population of bacteria (quoram sensing), carbon source and nutritional substrate, inter-cellular factors (like pheromon). Under the stressful condition for bacteria, ie ; heat, extream pH, in the presence of heavy metals, antibiotics, the bacteria induced the stress responsible genes including virulent genes.
2. Specific receptors for sensing environmental factors.
Each bacterium has a certain specific receptors for environmental factors, i … More .e., the most common one is the sensor component of two-component system. In C. perfringens, several systems have been identified, among which one for activation and the other for inhibition of production of toxin. In S. aureus, the receptors for zinc, alkaline, β-lactams were mostly identified.
3. Information transmitting network in bacteria.
Along with genomic analysis of C. perfringens, and that of Staphylococci, molecular basis of information transmitting system in bacteria has been made clear from receptor to effecter production as an sequential "molecular net work" with global regulatory system. This information is useful for the design of antibiotics in future.
4. Regulation at the level of transcription, translation, post translation and secretion from cell.
On basing upon those results, molecular net work of virulent factor production has been more clearly confirmed and the results will contribute to those who are looking for more specific effective anti-infection drugs and preventive measures. Less

Report

(5 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Kuroda M.et al.: "Chromosome-determined Zinc Responsible Operon czr in Staphylococcus aureus"Microbiol.Immunol.. 43. 115-125 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kato H.et al.: "Deletion in the repeating sequences of the toxin-A gene of toxin A-negative, toxin B-positive Ctostridium difficile strains"FEMS Microbiology Lett.. 175. 197-203 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamakawa K.et al.: "Inhibition of the enhanced toxin production by Clostridium difficile in biotin-limitedconditions"J.Med.Microbiol.. 47. 767-771 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kozaki S.et al.: "Characterization of Clostridium botulium type B neurotoxin associated with infant botulism in Japan"Infect.Immun.. 66. 4811-4816 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Aoki Y.et al.: "Characterization of small colony variants of methicillin-resistant Staphylococcus regrown in the presence of Arbekacin"J.Infect Cehmother.. 4. 107-11 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Banu S.et al.: "Identification of novel VirR/VirS-regulated genes in Clostridium perfrihgens"Mol.Microbiol.. 35. 1-12 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu, T., K. Ohtani, W. Ba-Thein, S. Inui, S. Nakamura, and H. Hayashi: "Characterization of a toxin-deficient Clostridium perfringens strain, KZ1340."Microbiol. Immunol.. 40. 141-145 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ba-thein, W., M. Lyristis, K. Ohtani, I. T. Nisbet, H. Hayashi, J. I. Rood and T. Shimizu: "The virR/virS locus regulates the transcription of genes encoding extra cellular toxin production in clostridium perfringens."J. Bacteriol. 178. 2514-2520 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani, K., M. Bando, T. Swe, S. Banu, M. Ooe, H. Hayashi, and T. Shimizu: "Collagenase gene (colA) is located in the 3'-flanking of the perfringolysin O (pfoA) locus in Clostridium perfringens."FEMS Microbiol. Lett.. 146. 155-160 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] William Ba-Thein, S. Inui, T. Shimizu, Tint Swe, Sayera Banu, K. Ohtani, M. Oe, N. Sakurai, S. Nakakura, and H. Hayashi: "Genomic Diversity in the pfoA region of theta-toxin-deficient strains of Clostridium perfringens"Microbiol. Immunol.. 41. 629-631 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Banu, Syera, Ohtani, K., Yaguchi, H., Sew, Tint, Cole, S. T., Hayashi, H. and Shimizu, T.: "Identification of novel VirR/VirS-regulated genes in Clostridium perfringens"Mol. Microbiol. 35. 1-12 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohatani, K., Takamura, H., Yaguchi, H., Hayashi, H. and Shimizu, T.: "Genetidc analysis of the ycgJ-metB-cycK-ygaG operon negatively regulated by the VirR/VirS system in Clostridium perfringens."Microbiol. Immunol.. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohta T., Nettikadan S., Tokumasu F., Ideno H., Ohta T., Nettikadan S., Tokumasu F., Ideno H., Abe Y., Kuroda M., Hayashi H., and Takeyasu K.: "Atomic Force Microscopy proposes a novel model for stem-loop structure that binds a heat shock protein in the Staphylococcus aureus HSP70 operon."Biochem. Biophys. Res. Commun.. 226. 730-734 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Aoki, Y., Yamauchi, Y., Hayashi, H., Takayama, Y. and tsuji, A.: "Characterization of samll colony variants of methicillin-resistant Staphylococcus aureus regrown in the presence of Arbekacin."J. Infect Cehmother.. 4. 107-111 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kuroda, Makoto, Daisuke Kobayashi, Kyoko Honda, Hideo Hayashi and Toshiko Ohta.: "The hsp operon is repressed by the hrc37 of the hsp70 operon in Staphylococcus aureus."Microbiol. Immunol.. 43. 19-27 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kuroda M., Hayashi H., and Ohta T.: "Chromosome-determined Zinc Responsible Operon czr in Staphylococcus aureus."Microbiology and Immunology. 43(2). 115-125 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murakami H., Matsumaru H., Kanamori M., Hayashi H., and Ohta T.: "Cell wall-affectingÅ@antibiotics induce expression of a novel gene drp35 in Staphylococcus aureus. Biochem."Biophys. Res. Commun.. 264(2). 348-351 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Kato, N. Kato, S. Katow, T. Maegawa, S. Nakamura and D. M. Lyerly.: "Deletion in the repeating sequences of the toxin A gene of toxin A- negative, toxin B-positive Clostridium difficile_strains"FEMS Microbiology Letters. 175. 197-203 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] D. Ikeda, T. Karasawa, K. Yamakawa, R. Tanaka, M. Namiki and S. Nakamura.: "Effect of isoleucine on toxin production by Clostridium difficile_in a defined medium Zbl."Bakt.. 287. 375-386 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Yamakawa, T. Karasawa, T. Ohta, H. Hayashi and S. Nakamura.: "Inhibition of the enhanced toxin production by Clostridium difficile in biotin-limited conditions"J. Med. Microbiol. 47. 767-771 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Kozai, Y. Kamata, T-I. Nishiki, H. Kakinuma, H. Maruyama, H. Takahashi, T. Karasawa, K. Yamakawa and sS. Nakamura.: "Characterization of Clostridium botulinum type B neurotoxin associated with infant botulism in Japan."Infect. Immun.. 66(10). 4811-4816 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] X. Meng, T. Karasawa, K. Zou, X. Kuang, X. Wang, C. Lu, C. Wang, K. Yamakawa and S. Nakamura: "Characterization of a neurotoxigenic Clostridium butyricum strain isolated from the food implicated in an outbreak of food-borne type E botulism"J. Clin. Microbiol.. 35(8). 2160-2162 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Karasawa, T. Maegawa, T. Nojiri, K. Yamakawa and S. Nakamura: "Effect of Arginine on Toxin Production by Clostridium difficile in Defined Medium Microbiol."Immunol.. 41(8). 581-585 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Kamiya, T. Yamamoto-Osaki, H. Taguchi, H. Yamaguchi, A. Ozawa and S. Nakamura: "Growth kinetics and pathogenicity of Clostridium difficile in continuous flow culture and mouse intestine."(eds) A. R. Eley and K. W. Bennett In Anaerobic pathogens, Sheffield Academic Press, Sheffield, England. 77-83 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kuroda M.et al.: "The hspoperon is repressed by the hrc37 of the hsp70 operon in Staphylococcus aureus"Microbiol.Immunol.. 43. 19-27 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kuroda M.et al.: "Chromosome-determined zinc responsible operon czr in Staphylococcus aureus"Microbiol.Immunol.. 43. 115-125 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Aoki Y,et al.: "Characterization of small colony variants of methicillin-resistant Staphylococcus aureus regrown in the presence of Arbekacin."J.Infect Chemother. 41. 107-111 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Murakami H,et al.: "Cell wall-affecting antibiotics induce expression of nevel gene,drp35,in Staphylococcus aureus."Biochem.Biophys.Res.Commun.. 264. 338-351 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Makino S.et al.: "Establishment of PCR system specific to Salmonella spp.and its application for the inspection of food and fecal samples."J.Vet.Med.Sci.. 61. 1245-1247 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Banu S.et al.: "Identification of novel VirR/VirS-regulated genes in Clostridium perfringens."Mol.Microbiol. 35. 1-12 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamakawa,K.,et al.: "Inhibition of enhanced roxin production by Clostridium difficile in biotin-limited conditions." J.Med.Microbiol.47. 767-771 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuroda,M.,et al.: "The hsp operon is repressed by the hrc37 of the hsp 70 operon in Staphylococcus aureus." Microbiol.Immunol.43. 19-27 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuroda,M.,et al.: "Choromosome-determined zinc responsible operon czr in Staphylococcus aureus." Microbiol.Immunol.43. 115-125 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Aoki,Y.,et al.: "Characterization of small colony variants of methicillin-resistant Staphylococcus aureus regrown in the presence of Arbekacin." J.Infect Chemother. 4. 107-111 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi,H.,et al.: "Salmonella Enteritidis." BIO Clinica. 12(14). 1048-1052 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 林 英生: "逆境にある細菌の生き方" 遺伝. 52(4). 55-60 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 林 英生・清水 徹: "毒素産生菌とその感染症" 竹田美文・本田武司編・医薬ジャーナル社, 255 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuroda,M., et al: "HSP70 and HSP60 operons are regulated by a transcriptional factor Hrc37 of the HSP70 operon in Staphylococcus cureus." J.Bacteriol. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohtani,K., et al: "Collagenase gene (colA)is locared in the 3^1-flanking region of the perfringolysin O(pfoA)locus in Clostridium perfringens." FEMS Microbiology Letters. 146. 155-159 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ba-Thein,W.et al: "Genomic diversity in the pfoA region of theta-roxin deficient strains of Clostridium perfringens." Microbiol.Immunol. 41(8). 629-631 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Karazawa,T., et al: "Effect of arginine on toxin production by Clostridium difficile in definedmedium." Microbiol.Immunol. 41(8). 581-585 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakamura,S., et al: "Effect of vitamins on toxin production by Clostridium difficile" Anaerobic pathogens. 85-91 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 太田敏子 他: "黄色ブドウ球菌のストレス応答遺伝子の発現調節" 臨床と微生物. 24. 229-230 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimizu,T., et al: "The Clostridia:Molecular Biologyand Pathogenesis (Acedcaic Press)" Regulation of taxin psoduction in Clostsidium perfringens, 451-470 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] I Makoto Kuroda,Toshiko Ohta,and HideoI Hayashi 1996: "Isolation and the gene cloning of an alkaline shock protein in methicillin resistant Staphylococcus aureus." Biochem.Biophys.Res.Comm.207. 978-984 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tohru Shimizu,K.Ohtani,W.Ba-Thein,S.Inui,S.Nakamura,and H.Hayashi.: "Characterization of a toxin-deficient Clostridium perfringens strain,KZ1340." Microbiol.Immunol.40. 141-145 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Toshiko Ohta,S.Nettikadan,F.Tokumase,H.Ideno,Y.Abe,M.Kuroda,H.Hayashi,K.Takeyasu: "Atomic force microscopy proposes a nevel model for stem-loop structure that binds a heat shock protein in the Staphylococcus aureus HSP70 operon." Biochem.Biophys.Res.Comm.226. 730-734 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ba-thein,W.,Lyristis,M.,Ohtani,K.,Nisbet,I.T.,Hayashi,H.,Rood,J.I,and Shimizu,T.: "The virR/virS Locus regulates the transcription of genes encoding extracellular toxin production in Clostridium perfringens." J.Bacteriol.178. 2514-2520 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Ohtani,M.Bando,T.Swe,S.Banu,M.Ooe,H.Hayashi,and T.Shimizu.: "Collagenase gene (colA) is located in the 3'-flanking region of the perfringolysin O (pfoA) locus in Clostridium perfringens." FEMS Microbiol..Lett.146. 155-160 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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