Studies on bioactive metabolites produced by pathogenic Nocardia

致病性诺卡氏菌产生的生物活性代谢物的研究

• 批准号: 04670241
• 负责人: MIKAMI Yuzuru
• 金额: $ 0.32万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670241/
• 关键词: Pathogenicity; 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

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

在对临床分离的致病性诺卡氏菌的毒性物质研究中，发现一株新分离的皮肤诺卡氏菌（Nocardia otitidiscaviarum）产生一种毒性物质HS-6，该物质在体外具有很强的毒性。我们进一步的研究发现HS-6具有有趣的生物学活性，如在肝脏中积累甘油三酯。这些结果促使我们从致病性诺卡氏菌中分离新的生物活性物质，包括毒性物质。本研究筛选出了5株产生物活性物质的产菌。对所选致病性诺卡氏菌的生物活性物质进行分离研究，从IFM-075菌株的菌丝体中分离出一种新的蒽环类化合物（SO-075 R1），经鉴定为巴西诺卡氏菌。它对培养的细胞没有如此大的毒性，显示出<50>对Vero细胞的艾德^值为50 μ g/ml。对革兰氏阳性菌也有活性，但对革兰氏阴性菌无活性。虽然它没有抗肿瘤活性，但对DNA病毒如HSV有抗病毒活性。我们还从巴西猪笼草IFM 075中分离出三个次要组分，命名为M-3、M-4和M-13-1。结构研究表明，它们是新的还原蒽环类化合物。生物活性的研究正在进行中。对这些化合物的生物合成研究表明，M-3、M-4和M-13-1可能是由SO-075 R1或其蒽环酮生物还原而得。本文报道了致病性诺卡氏菌的耐药模式。在对耐药机制的研究中，我们发现了诺卡氏菌对抗生素的失活机制。这些包括利福平的磷酸化和糖基化，以及大环内酯类化合物的糖基化、磷酸化、还原和转酰化。通过这些研究，我们

项目成果

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

Mikami,Y.et al.：“SO-075R1，一种由巴西诺卡氏菌产生的新变霉素衍生物”J.Antibiotics。

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)

Jo Mikami、Katsukiyo Yazawa（撰稿人）：“放线菌的鉴定方法” Makoto Miyaji、Kazuko Nishimura、Jun Uno（编）广川书店，285（1992）

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)

Akio Maeda 和其他 5 人：“新型变霉素类抗生素 S0-075R1 的生产者和生物活性”《抗生素杂志》45。1848-1852（1992）。

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)

Yuzuru Mikami 和其他 4 人：“通过碱性介质中含有的拟青霉毒素从土壤中选择性分离淡紫拟青霉菌株”Ball.J.F.C.C.8 (1992)。

Maeda,A.et al.: "The producer and biological activiteis of SO-075R1,a new mutactimycin group antibiotic" J.Antibiotics. 45. 1848-1852 (1992)

Maeda,A.et al.：“新型变霉素类抗生素 SO-075R1 的生产者和生物活性”J.Antibiotics。