A strain of a new Pseudomonas species produced the aminoglycoside antibiotic complex, sorbistin, which was separated by ion-exchange chromatography into three bio-active components A1, A2 and B, and two bio-inactive components C and D. Sorbistins A1, A2 and B showed moderate intrinsic activity against a wide range of bacterial species and inhibited most of the aminoglycoside-resistant organisms. Sorbistin A1 exhibited the highest activity among the three bio-active components. Sorbistins showed low order of acute toxicity in mice.
The sorbistin-producing organism, Pseudomonas sorbicinii nov. sp., has been isolated from a soil sample by psychrophilic pre-incubation technique. The organism resembles P. fluorescens in many respects but differs in some of the important physiological characteristics such as oxidase production, media specificity for the production of fluorescent pigment, and carbohydrate utilization pattern. The type strain, No. D946-B83, has been deposited under the numbers ATCC 31086 and FERM-P 3328.
The structures of sorbistins A1, A2, B, C and D have been determined including stereochemistry. Sorbistins A1, A2 and B are composed of a 4-acyl-amino-4-deoxy-D-glucose and 1, 4-diamino-1, 4-dideoxy-D-sorbitol, the latter compound being hitherto undescribed in literature. Sorbistins C and D have the same aglycone of 1, 4-diamino-1, 4-dideoxy-D-sorbitol, which is linked with D-glucose and 4-amino-4-deoxy-D-glucose, respectively, through a glycosidic bond.
An actinomycete, strain No. T-1124, was found to produce new macrolide antibiotics, juvenimicins. Based on the results of taxonomic studies, the strain was considered to be a new variety of Micromonospora chalcea and the name Micromonospora chalcea var. izumensis is proposed. This strain also produced everninomicin. The production of juvenimicins was stimulated by addition of ferrous sulfate and magnesium sulfate in the fermentation medium. Among juvenimicins, juvenimicin A3 exhibited the most potent antimicrobial activities against gram-positive bacteria and furthermore was active against gram-negative bacteria.
A series of new macrolide antibiotics was isolated from the culture filtrate of Micromonospora chalcea var. izumensis. The fat-soluble basic complex consisted of eight components which were named juvenimicin A1-A4 and B1-B4. Juvenimicin A3 was found to be identical with rosamicin and the structures of four of the other components (JVM A2, A4, B1 and B3) have been elucidated. Juvenimicin A2 has a methyl group at position 6 instead of the formyl-methyl group of juvenimicin A3. Juvenimicin A4, B1 and B3 possess a hydroxyethyl group at position 6. Juvenimicin A4 and B1 differ from each other in the nature of the chromophore. Juvenimicin B3 differs from juvenimicin B1 in that a hydroxymethyl group is present at position 14 in the former.
A new variety of Streptomyces hygroscopicus was isolated from a Kalamazoo soil. This isolate is described and identified as var. geldanus. When fermented in preferential media it produces geldanamycin, nigericin, nocardamine, and a libanamycin-like activity. Fermentation conditions, chromatographic separation, and antimicrobial spectra of the antibiotics are given.
Additional parameters for the chloramphenicol acetyltransferase (CAT) activity in spores of S. griseus are substantiated. A linear increase inactivity was observed with increasing spore number up to a concentration of 5×1010 spores/ml. Similarly an increase of the chloramphenicol concentration up to 500 μg/ml increased the activity. However, a drastic decrease in activity was noted above this level suggesting inhibition of the enzyme by the substrate. The CAT activity in the spores was highly influenced by the pH of the medium reaching a maximum at pH 6.5. This may suggest that CAT is apparently located to the outer surface of the spores and therefore very sensitive to variations in pH of the medium. The CAT showed a marked specificity for D-threo and D-erythro chloramphenicol, while no activity was observed with L-isomers. The enzyme acetylates D, L-erythro dechlor-chloramphenicol with a yield of 45% as compared to the D-threo parent antibiotic. While the tyrosinase characteristic (melanin formation) of S. griseus was eliminated by acriflavine or ethidium bromide treatment the CAT characteristic was persistent. The melanin negative variants retained all other properties of the parent strain including the production of antimicrobial agents; and revertants were not detected. The results suggest that the tyrosinase determinant gene is apparently located on an extrachromosomal element (plasmid). On the other hand, the location of the gene for CAT is not assigned yet. The nature of CAT in growing cells and the spores of S. griseus was investigated. The results show that CAT accumulated during the sporulation phase or the vegetative growth is inducible in nature; therefore the morphogenetic sequence in the strain bears no influence on CAT induction.
Daunomycinone, aglycone of the anthracycline antibiotic daunomycin, was transformed by a washed mycelia of Streptomyces aureofaciens B-96 in a buffer solution containing sucrose; the obtained product, dihydrodaunomycinone(9-(1-hydroxyethyl)-7, 8, 9, 10-tetrahydro-6, 7, 9, 11- tetrahydroxy-4-methoxy-5, 12-naphthacenequinone), was identified by measuring basic physicochemical characteristics (IR, UV and visible spectra, mass spectra and NMR, optical rotation and m. p.).
Glycosidation of narbonolide with mycaminose was attempted by feeding narbonolide during the fermentation of a parent or a mutant strain of Streptomyces platensis, a producer of 16-membered macrolide antibiotics, platenomycins. As a result, two new compounds I and II were isolated from the fermentation broth and identified as 5-O-mycaminosyl narbonolide (I) and 9-dihydro-5-O-mycaminosyl narbonolide (II), respectively. Physicochemical and antimicrobial properties of I and II are also referred to.
Mass spectra of platenolides-biosynthetic precursors of the 16-membered macrolide antibìotics, platenomycins-and their derivatives are discussed in detail especially in connection with structure elucidation. Mass spectrometry was of great use in establishing the structures for platenolides I (1) and II (2).
Reduction of the nitroso group in streptozotocin (1a) has led to cyclized products rather than a semicarbazide (1c). Some analogs (1e, 9a, 9b, 9c and 9d) of streptozotocin in which the nitroso group was replaced by other groups have been prepared.
The synthesis of 7-(2-aminomethylphenylacetamido)-3-(1-carboxymethyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (BL-S786) is described and the antimicrobial activities are compared with cefazolin and cefamandole. The compound exhibits broad antimicrobial spectrum, produces high intramuscular blood levels in mice and demonstrates a high degree of therapeutic efficacy in experimental bacterial infections in rodents.
The minimal inhibitory concentrations (MIC) of various antibiotics and fungicides for Enwinia carotovora, Pseudomonas coronafaciens var. atropurpurea, P. lachrymans, Alternaria mali, A. kikuchiana, Pyricularia oryzae, Botrytis sp. and Sclerotinia sp. isolated from diseased plants in various localities of Japan were examined to enable the isolates to be grouped into sensitive and resistant strains. To minimize the effects of various variable conditions, MIC of isolates were pooled for either 2 or 3 years and were plotted in a single figure. The grouping values were determined on the basis of MIC values of the antibiotics and agricultural chemicals on phytopathogenic bacteria and fungi under investigations. The relationships between grouping values for isolates of bacteria and fungi and the control of disease on the plants correlated to each other were studied.
A simplified method to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of β-lactam antibiotics on agar plates is described. MIC values were determined on agar plates for benzylpenicillin, methicillin and cephalothin using Staphylococcus aureus and Klebsiella pneumoniae. A β-lactamase solution was then sprayed onto the plates to inactivate the drug(s). After further incubation at 37°C overnight, the minimal concentration at which no test bacteria were visible on the plates was defined as MBC. Both MIC and MBC values decreased with decreased inoculum size. The two values were almost coincidental when high dilutions were used as the inocula. These values were compared with those obtained by the conventional broth dilution method. In this study, MIC as well as MBC values determined by the simplified method were generally smaller than the values determined by the broth dilution technique.