Search For Novel Antibiotics Research Articles

Diversity in aminoglycoside antibiotic resistance of actinomycetes and its exploitation in the search for novel antibiotics

Wide varieties of multiple aminoglycoside antibiotic (AG) resistance that are not found in knownStreptomyces cultures were found among actinomycetes isolated as AG-resistant. Screening of about 170 AG-resistant isolates demonstrated their high probability (63%) of antibiotic production including the production of eight different AGs. We found specific AG-resistance patterns correlating to the productivity of specific AGs and established an AG-targeted assay system using AG producers as test organisms. Consequently, AG-directed screening totally on the basis of multiple AG-resistance was established. Necessity of biochemical and genetic studies on primary metabolism in order to find a new basis to search for novel metabolites is also discussed.

The suppressive effect of pyrrole-2-carboxylic acid on platelet aggregation

In the course of a search for novel antibiotics, an antiplatelet substance was isolated from the fermentation broth of Streptomyces sp. No. 82-85. Thereafter, the active substance was identified as pyrrole-2-carboxylic acid (P2C) by structural studies. The effects of P2C on adenosine diphosphate (ADP)-, arachidonic acid-, collagen- or tumor cell-induced platelet aggregation were examined in vitro and ex vivo. In in vitro studies, P2C (25-100 micrograms/ml) suppressed the aggregation of platelets of normal Wistar rats. The intraperitoneal administration of P2C (200 mg/kg) to rats and rabbits suppressed platelet aggregation induced by ADP, arachidonic acid and collagen when examined for 0.5-3 hours after administration. The agent also suppressed platelet aggregation induced by both mouse syngenic tumors, Meth-A fibrosarcoma and IMC carcinoma in vitro.