A complex of 18-membered macrolide antibiotics has been discovered in the fermentation broth of strain AB718C-41. The producing culture, isolated from a soil sample collected in Hamden,Connecticut, was identified as a strain of Dactylosporangium aurantiacum and was designated D. aurantiacum subsp. hamdenensis subsp. nov. The antibiotic complex was produced in a NewBrunswick 150-liter fermentor using a mediumconsisting of glucose, soybean oil, soybean flour, beef extract and inorganic salts. Several of the antibiotics were active against sensitive and multiple antibiotic-resistant strains of pathogenic Gram-positive bacteria.
Determination of the mechanism of action of FK506and cyclosporin A has yielded new molecular targets involved in signal transduction during T cell activation. A commontarget of FK506 and cyclosporin A is inhibition of activation of the NFATtranscription factor, for which a specific binding region is present in the promoter of the IL-2 gene. A reporter gene assay has been used to screen for agents that interfere with this early step in T cell activation. Simple aromatic compoundsthat block NFAT-dependent transcription and showin vitro immunosuppressiveactivity were isolated from the broth and mycelia of two Streptomyces sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic.
The dorrigocins are newsecondary metabolites produced by submerged fermentation of a streptomycete which was isolated from a soil sample collected in Australia. The dorrigocins show moderate antifungal activity and reverse the morphology of ray-transformed NIH/3T3cells from a transformed phenotype to a normal one. The producing culture was identified as Streptomyces platensis subsp. rosaceus strain AB198 1F-75.The dorrigocins are novel glutarimide antifungal antibiotics discovered in the fermentation broth and myceliumof Streptomyces platensis subsp. rosaceus strain AB198 1F-75. This paper describes the taxonomy of the producing strain and the fermentation, antifungal and antitumor activity of the dorrigocins. The isolation, structural elucidation, biological properties and mechanism of action of these compounds are described in accompanying publication1>2).
Materials and Methods
Micro organismsStrain AB1981F-75 was isolated from soil collected on the Dorrigo plateau in NewSouth Wales, Australia. A subculture of the microorganism was deposited at
A new method is described for the selective isolation of species of Myxococcus directly from soil by dilution plating. The method involves suppression of competing microorganisms with antibiotics combined with air drying and wet heat treatment of soils. Fungi were eliminated by supplementing the plating medium with cycloheximide and nystatin. Non-sporulating bacteria were controlled by air drying soils and then heating aqueous soil dilutions for 10 min at 56 degrees C. The predominant sporulating bacteria in soil, Streptomyces and Bacillus, were suppressed by adding either tiacumicin B, ristocetin or vancomycin to the medium. Swarming of Myxococcus colonies was controlled with a casein digest-yeast extract plating medium (CY-C10 agar). Ultrasound treatment of soil suspensions gave the highest number of Myxococcus colonies in the soils studied, but these cultures could be recovered without ultrasound. Strains of Myxococcus fulvus, M. xanthus, M. coralloides, M. stipitatus and M. virescens were isolated from soil using this technique. Soils examined yielded one or two Myxococcus species per sample.
A whole-cell Candida albicans assay based on the protection of growth with sorbitol and characterization of changes in cell morphology, was used to detect novel antifungal agents, inhibitors of fungal cell wall syn
Coumamidines are water-soluble basic antibiotics related to the glycocinnamoylspermidines. They are produced by a soil isolate designated Saccharopolyspora sp. AB 1167L-65. The coumamidines have broad spectrum activity and were selected in a screen for substances which inhibit Pseudomonas aeruginosa.Coumamidines, a complex of water-soluble basic antibiotics, have been found in the fermentation broth of a soil isolate, designated Saccharopolyspora sp. AB1167L-65. They are related to the glycocinnamoylspermidines0 (cinodines). This paper describes the discovery of the coumamidines, their production by fermentation and the taxonomy of the producing organism. The isolation and structure elucidation of the coumamidines and their biological properties are given in companion papers2>3).
Materials and MethodsMicro organisms Strain AB1167L-65 was isolated from a soil collected in a woodedarea near Russell, Kentucky. The soil was air-dried overnight, then heated for 1 hour at 120°C. Dilutions of the heated soil were plated on a medium consisting of soluble starch 0.1 %, KNO30.1 %, K2HPO40.05%, MgSO4-7H2O 0.1 %, yeast extract (Difco) 0.01 %, 1 ml of trace element solution4) per liter and agar 2%. Cycloheximide (50^g/ml), nystatin (50^g/ml) and gentamicin (2.5^g/ml) were added to the medium. The plates were incubated for 30 days at 30°C. Pseudomonas aeruginosa K799/61 was obtained from Zimmermann5). Other strains used in the screen were from the American Type Culture Collection (ATCC)or from the stock culture collection in our laboratory.
Discovery ScreenA two stage screen was used to discover substances with activity against P. aeruginosa. Agar plugs were cut from cultures growing on the surface of a mediumcontaining glucose monohydrate 2 %, Lexein F-152 liquid peptone (Inolex) 1 %, yeast extract (Difco) 0.1 %, molasses (Del Monte) 0.5%, CaCO30.2% and agar 2%. The plugs were placed on the surface of streptomycin assay agar with yeast extract (BBL) seeded with P. aeruginosa K799/61. This strain is a mutant with increased susceptibility to various antibiotics (novobiocin, tetracycline, erythromycin and others), apparently due to the failure of the outer layers of its cell envelope to act as an adequate permeability barrier5). Cultures which inhibited this ultra-sensitive strain of Pseudomonas were fermented in liquid shaken culture. Concentrates of the fermentation broths were tested for inhibition of clinical isolates of P. aeruginosa and other bacteria.
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