Studies on bioactive metabolites produced by pathogenic Nocardia

在对临床分离的致病性诺卡氏菌毒性物质的研究中，发现一株新的抗皮肤诺卡氏菌产生一种毒性物质HS-6，其体外毒性较强。我们的进一步研究发现HS-6具有有趣的生物学活性，例如在肝脏中积累甘油三酯。这些结果促使我们从致病诺卡氏菌中分离出包括有毒物质在内的新的生物活性物质。我们的筛选研究可以筛选出5株产生物活性物质的嗜酸诺卡氏菌(S)。通过对所选致病诺卡氏菌生物活性物质的分离研究，从IFM-075菌株的菌丝体中分离得到一种新的蒽类化合物(SO-075R1)，经鉴定为巴西诺卡氏菌。对培养细胞毒性较小，对Vero细胞的ED值为50µg/ml。对革兰氏阳性菌也有抑制作用，但对革兰氏阳性菌无抑制作用，但对单纯疱疹病毒等DNA病毒有一定的抗病毒活性。我们还从巴西新月球藻IFM 075中分离出三个次要成分，分别命名为M-3、M-4和M-13-1。结构研究表明，它们是新的还原态的蒽环类化合物。有关生物活性的研究目前正在进行中。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-075R1或其蒽环酮生物还原而来的。我们曾报道，致病诺卡氏菌表现出物种特异性的耐药模式。在对耐药机制的研究中，我们发现诺卡氏菌对抗生素有有趣的灭活机制。其中包括利福平的磷酸化和糖基化，以及大环内酯类抗生素的糖基化、磷酸化、还原和转酰化。通过这些研究，我们报告了

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