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Studies on bioactive metabolites produced by pathogenic Nocardia

Research Project

Project/Area Number 04670241
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 植物保護
Research InstitutionChiba University

Principal Investigator

MIKAMI Yuzuru  Chiba Uni. Res. Cent. Patho. Fungi and Microb. Toxicoses, Dept. of chemother. Associate Prof., 真核微生物研究センター, 助教授 (40092100)

Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
KeywordsPathogenicity / Nocardia / Actinomycetes / Bioadvesubstance* / ノカルジア症 / トキシン / HS-6 / SO-75RI / 抗ウィルス活性 / アンスラサイクリン
Research Abstract

During our studies on the toxic substances from clinically isolated pathogenic Nocardia, a newisolate idantificed as Nocardia otitidiscaviarum (from cutaneous nocardiosis) was found to produce a toxic substance calaled HS-6 which had strong in vitro as toxicity. Our further studies revealed that HS-6 ahows interesting biological activities such as accmulation of triglyceride in the liver. these results prompted us to isolate new bioactive substances includ-ing toxic ones from pathogenic Nocardia. Our screening studies could select 5 strains of phthoge-nic Nocardia as producers of bioactive substance(s). Isolation studies on bioactive substances from the selected phthogenic Nocardia resulted in an isolation of a new anthracyline compound (SO-075R1) from the mycelium of IFM-075 strain, which was identificed as Nocardia brasiliensis. It was not so toxic to cultured cells, showing ED^<50> value of 50 mug/ml against Vero cells. Itwas also active aginst gram-positive bacteria, but not active against gram-megative bacteria., Although it showed no antitumor activiteis, it showed antiviral activity against DNA virus such as HSV.Detail studies on other biological activities are conducted. We also isolated three minor components, disignated M-3, M-4 and M-13-1 from N.Brasiliensis IFM 075. The structural studies showed that they are new reduced anthracycline related compounds. Studies on biological acti-vities are now in progress. Biosynthetic studies on the compounds suggested that M-3, M-4 and M-13-1 might be derived by bioreduction of SO-075R1 or its anthracyclinone. We had reprted that phthogenic Nocardia showed species-specific resistant patterns. During our studies on the mechanisms of the resistance, we found interesting inactivation mechanisms of the antibiotics by the Nocardia. These include phosphorylation and glycosylation of rifampicin, and glycosylation, phosphorylation, reduction and transacylation of macrolide antibioitcs. Throughtout these studies, we repo

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Mikami,Y.et al.: "SO-075R1,a new mutactimycin derivative produced by Nocardia brasiliensis" J.Antibiotics. 45. 995-997 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Maeda,A.et al.: "The producer and biological activiteis of SO-075R1,a new mutactimycin group antibiotic" J.Antibiotics. 45. 1848-1852 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yazawa,K.et al: "Inactivation of rifampin by Nocardia brasiliensis" Antimicrob.Agents and Chemother.37. 1313-1317 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Masataro,H.et al.: "Localized cutaneous nocardiosis in Japan" Mycopathol.117. 133-138 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morisaki,N.et al.: "Incativated products of rifampicin by pathogenic Nocardia spp.:Structures of glycosylated and phosphorylated metabolites of rifampicin and 3-fomylrifamycin SV" J.Antibiotics. 46. 1605-1610 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yazawa,K.et al.: "Phosphorylative inactivation of rifampicin by Nocardia otitidiscaviarum" J.Antimicrob.Chemother.(in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 三上襄、矢沢勝清(分担): "放線菌の同定法" 宮治誠、西村和子、宇野潤(編集) 広川書店, 285 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 三上襄、矢沢勝清(分担): "真菌症の臨床検査 菌学的検査同定法:放線菌" 小川秀興(編) 金原出版, 238 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] k. Yazawa, S.Ohashi, A.Maeda, M.Akao, M.Ishibashi, J.Kobayashi and C.Yamazaki: "SO-075R1, a new mutactimycin derivative produced by Nocardia brasiliensis." J.Antibiot. 45. 995-997 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Maeda, a., K.Yazawa, Y., Mikami, M.Ishibashi and J.Kabayashi: "The producer and biological activiteis of SO-075R1, a new mutactimycin group antibiotic." J.Antibiot. 45. 1848-1852 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morisaki, N., S, Iwasaki, K.Yazawa, Y.Mikami adn A.Maeda: "Incati vated products of refampicin by phthogenic Nocardia spp. : Structures of glycosylated and phosphoryated metabolites of rifampicin and 3-fomyl-rifamycin SV." J.Antibiot. 46. 1605-1610 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yazawa, K., Y.Mikami, A.Maeda, M.Akao, N.Morisaki and S.Iwasaki: "Inactivation of rifampin by Nocardia brasiliensis." Antimicrob. Agents and Chemother. 37. 1313-1317 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yazawa, K., Y.Mikami, A.Maeda, N.Morisaki and S.Iwasaki: "Phosphorylative inactivation of rifampicin by Nocardia otitidiscaviarum." J.Antimicrob. Chemother.(in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morisaki 他: "Inactivated products of rifampicin by pathogenic Nocardia spp." J.Antibiotics. 46. 1605-1610 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yazawa 他: "Inactivation of rifampin by Nocardia brasiliensis" Antimiuob.Agents and Chemother.37. 1313-1317 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masataro 他: "Localized cataneous nocardiosis in Japan" Mycopathol.117. 133-138 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yazawa 他: "Phosphorylative inactivation of rifampin by N.otitidiscaviaton." J.Antimiuob.Chemother.(印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 三上襄,矢沢勝清(分担): "真菌症の臨床検査「菌学的検査同定法」放線菌" 小川秀興(編) 金原出版, 238 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akio Maeda 他5名: "The producer and biological activities of S0-075R1,a new mutactimycin group antibiotic" Journal of Antibiotics. 45. 1848-1852 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yuzuru Mikami 他7名: "SO-75R1,a new mutactimycin derivative produced by Nocardia brasiliensis" Journal of Antibiotics. 45. 995-997 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kiyoshi Terao 他6名: "Light and electron microscopic studies on experimental rocardia-toxicosis in mice" Mycopathologia. 119. 115-125 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akinori Kubo 他7名: "A Synthesis of 4-cyano-hexahydro-2H-Benzo(b)guino-lizine-7,-10-dione as a simplemodel compound of saframycin A" Heterocycles. 34. 1201-1211 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yuzuru Mikami 他4名: "Selective isolation of Paecilomyces lilacinus strains from soil by paecilotoxin contained in an alkaline medium" Ball.J.F.C.C.8. 65-70 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Katsukiyo Yazawa 他5名: "In-vitro activity of new carbapenem antibiotics:comparatire studies with meropenem,L-627 and imipenem against pathogenic Nocardia spp" Journal of Antimicrobiol Chemotherapy. 29. 169-172 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 三上 襄,矢沢 勝清(分担): "「病原性放線菌の同定法」p.183-201" 宮治 誠,西村 和子,宇野 潤(編集) 廣川書店, 285 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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