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H Thrum

Publications and source records attributed to H Thrum.

18 recordsLinked to original sources
PubMed1979

Netropsin, a DNA-binding oligopeptide structural and binding studies.

The crystal structure of netropsin, an oligopeptide which binds to DNA, has been determined. The molecule is bowed with the amide groups on the concave side, and the carbonyl and methyl groups on the convex side. The amide groups participate in extensive hydrogen bonding with water molecules; the charged amino end groups interact with the sulfate anions. Binding of netropsin to poly(dA) . poly(dT) under conditions of different ionic strength was also studied. Utilizing the crystallographic as well as the binding data, it is possible to build a model which explains the specificity of this antibiotic.

Circular Dichroism↗
PubMed1979

[Effect of polyene antibiotics and their perhydrovderivatives on intact cells and protoplasts of yeast Candida guilliermondii].

Perhydroderivatives of polyene antibiotics have a much lower activity against eukaryotic cells than the polyene antibiotics itself. Bacterial cells are normally resistant against most polyene antibiotics and their perhydroderivatives. In earlier experiments with wall less L-form cells of Escherichia coli we have shown that the bacterial cell wall may be responsible for the resistance of the intact bacterial cells against polyene antibiotics and their perhydroderivatives by masking internal target sites. In the present paper we studied the effect of polyene antibiotics and their perhydroderivatives on intact cells and protoplasts of Candida guilliermondii. Our experiments have shown that most of the perhydroderivatives studied had a lower activity against intact cells as well as protoplasts than the corresponding polyene antibiotics. This means that in the case of eukaryotic cells the cell wall as a penetration barrier cannot mainly be responsible for the low activity of perhydroderivatives. The results are compared with those obtained previously with intact cells and protoplast type L-form cells of E. coli.

Anti-Bacterial Agents↗
PubMed1979

Regulative influence of o-aminobenzoic acid on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b. IV. Bistability of metabolism and the mechanism of action of aminobenzoic acids.

Using the semi-continuous cultivation technique we could establish that specifically in Streptomyces noursei JA 3890b during growth on a medium supplied with D,L-alanine, NH4+, and maize starch there are two different phenotypes of the organism and stationary states of metabolism, respectively. The expression of either the metabolic state I with an enhanced capacity to oxidative deamination of alanine via the NAD+-dependent alanaine dehydrogenase or the metabolic state 2 which may be characterized by the preferred use of ammonium ions via the NADP+-dependent glutamate dehydrogenase was shown to depend strongly on the conditions of inoculum cultivation. When the amino acid permeases were derepressed by cultivating the inoculum cells on amino acid media, probably due to the defective mechanism of negative feedback control of amino acid influx in this strain an abnormously high uptake of alanine was observed that, consequently, was correlated to the enhanced oxidation of this amino acid as well as to the intensive production of ammonia within the cell. This overproduction of cellular NH4+ seems to bring about the subsequent repression of biosynthetic glutamate dehydrogenase and so on the accumulation of ammonia autocatalytically may rise up (metabolic state I). On the other hand, if the influx of alanine was kept low and the NADH oxidation was less efficient, respectively, or when there was high cellular activity of glutamate dehydrogenase the level of ammonia never did exceed the respressory limit and, accordingly, the expression of the metabolic state 2 was observed. Switching-over of metabolic flux from the state 2 towards the state 1 can be brought about either by increasing the level of nitrogen sources in the medium or by adding buffers pH greater than 7.5. In contrast, decrease of cellular level of NH4+ was shown to induce the transition of metabolic state 1 into the state 2. This can be achieved not only by limitation of nitrogen source but also by adding different aminobenzoic acids and, alternatively, effectors of membrane function (short-chain alcohols), inhibitors of cytochrome oxidases (sodium azide, potassium cyanide), heavy metal (Fe++)-chelating agents (catechol, 2,5'-dipyridyl, o-phenanthroline), beta-alanine, and buffers pH less than 7. This suggests that these effectors are capable of preventing the abnormously high influx of amino acids as well as its wasteful catabolism within the cell of S. noursei JA 3890b. Therefore, it seems likely that by this way the aminobenzoic acids and similar effectors can diminish the catabolite repression or inhibition of secondary metabolism by cellular excess of some nitrogen compounds in good agreement with its well-known stimulatory action on the biosynthesis of the antibiotic nourseothricin in this strain.

Alanine↗
PubMed1979

Alcohol-induced switching over of metabolic flux in Streptomyces noursei JA0 3890b.

Short-chain alcohols, benzyl alcohol and Tween 20 were found capable of switching over the metabolic flux in Streptomyces noursei JA 3890b from the preference of oxidative deamination of alanine towards the reinforced acquisition of NH4+. These changes were correlated to the decrease of the ratio of saturated to olefinic fatty acids in the mycelium, suggesting that alcohols and other polar lipophilic compounds can interfere with the biosynthesis and the function of the cytoplasmic membrane in Streptomyces.

1-Propanol↗
PubMed1978

Regulative influence of o-aminobenzoic acid on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b. III. Change of redox state of nicotinamide-adenine-dinucleotides in the presence of aminobenzoic acids.

o-Aminobenzoic acid (OABA, anthranilic acid) and related compounds which are known to stimulate the biosynthesis of streptothricin-type antibiotic nourseothricin by Streptomyces noursei JA 3890b were found to increase strongly the NADH/NAD+ ratio in growing mycelium of this strain suggesting that these effectors are capable of interfering with the function of the respiratory chain. In parallel, a complex shift of metabolism was induced shown by simultaneous alteration of mycelial activities of alanine dehydrogenase, glutamine synthetase, and glutamate dehydrogenase. These changes may be responsible for the observed delay of amino acid catabolism and may improve the precursor supply of the secondary metabolism.

Alanine↗
PubMed1978

Streptothricin F, an inhibitor of protein synthesis with miscoding activity.

The effect of streptothricin F on macromolecular syntheses in intact cells and cell-free protein synthesis of E. coli was studied. The results indicate that protein synthesis is the primary site of inhibition by streptothricin F in growing E. coli cells. Cell-free polypeptide synthesis from E. coli directed by poly (U) was inhibited, while poly (A) and poly (C) directed polypeptide syntheses were both stimulated by the drug. Furthermore, streptothricin F caused misreading of translation of poly (U), poly (A) and poly (C) directed protein syntheses in E. coli systems. The extent of misreading by streptothricin F increases with increasing drug concentrations. The results are compared with those of other miscoding antibiotics. In rat liver extracts protein directed by poly (U) or endogenous mRNA was not inhibited.

Animals↗
PubMed1977

[Classes of antibiotics and their mechanisms of action].

The antibiotics used in the chemotherapy of microbial infections are considered with respect to their antimicrobial spectra and their mechanisms of action, respectively. The sites of action of the different groups of antibiotics interfering with the same cellular processes are discussed. According to their primary actions on sensible cells the antimicrobial antibiotics are divided into four groups: 1. Inhibitors of the biosynthesis of the bacterial cell wall 2. Inhibitors of the bacterial protein synthesis 3. Inhibitors of the nucleic acid metabolism 4. Membrane-active antibiotics.

Anti-Bacterial Agents↗
PubMed1977

Biosynthesis of streptolidine moiety of streptothricins by Streptomyces noursei JA 3890b.

The incorporation of uniformly 14C-labeled compounds into the streptothricin-type antibiotic nourseothricin was studied with a strain of Streptomyces noursei JA 3890b. 6.5% of radioactivity from U-14C-L-arginine was incorporated into the antibiotic, while glutamic acid, aspartic acid, alanine, proline, glycine and leucine displayed much lower incorporations. Furhtermore, 95% of the activity incorporated from arginine was located in the streptolidine moiety supporting the suggestion that this subunit of streptothricin antibiotics is formed via the dehydroarginine pathway.

Amino Acids↗
PubMed1977

Biosynthetic studies on the macrolide antibiotic turimycin using 14C-labeled precursors.

Using a strain of Streptomyces hygroscopicus JA 6599 several 14C-compounds were investigates as potential precursors of the macrolide antibiotic turimycin followed by partial degradation to localize the radioactivity. L-Methionine-14C-methyl and n-butyrate-1-14C were incorporated exclusively and in a specific manner. The incorporation ratios were dependent on the addition time of the precursors. Studies of the incorporation of acylmycaroses and demycarosyl turimycin into the antibiotic are also reported.

Anti-Bacterial Agents↗
PubMed1976

Effects of polyene macrolide antibiotics on normal and protoplast type L-form cells of Escherichia coli W1655F+.

The action of the polyene macrolide antibiotics mycotrienin, pimaricin, lucensomycin, tetramycin, rimocidin, nystatin, filipin, lagosin, pentaene antibiotic 2814P, flavomycoin, flavofungin, hexaene antibiotic 5001P, and candicidin, including perhydro derivatives of them, on wall-less stable protoplast type L-form and normal rod form cells of E. coli W1655F+ was studied. No inhibition of the normal rod form cells was detected. In contrast to these results the growth of the L-form cells was inhibited by all of the substances tested, with the exception of pimaricin. Further experiments have shown that the differences in sensitivity of normal and L-form cells cannot be explained by differences in sterol content, the target site of polyene antibiotics in sensitive eukaryotic cells. According to our results it is obvious that the cell wall of the normal cells functions as a penetration barrier to polyene antibiotics.

Anti-Bacterial Agents↗
PubMed1975

[Precursor formation and biosynthesis of the macrolide antibiotic a 6599 (turimycin) by streptomyces hygroscopicus JA 6599].

The possible role of some metabolic systems producing acetyl-CoA, and methylmalonyl-CoA as initial precursors in the biosynthesis of the macrolide antibiotic A 6599 by Streptomyces hygroscopicus JA 6599 was studied. The activities of pyruvate decarboxylase exceeded in two higher producing strains about twofold those found in the mycelium of a lower producing one suggesting that in this organism an enhanced production of acetyl-CoA should be one of the prerequisites necessary for an improved antibiotic biosynthesis. No clear interrelationship was established, however, between the biosynthesis of the secondary metabolite A 6599 on the one hand and the acetate and propionate kinase content on the other hand. In S. hygroscopicus JA 6599 the carboxylation of acetyl-CoA or propionyl-CoA seems to be the major pathway giving malonyl-CoA or methylmalonyl-CoA, respectively. Thus, the activities of acetyl-CoA and propionyl-CoA carboxylases corresponded with both the levels of antibiotic production in several strains and with variations observed in the specific antibiotic production rate during the cultivation. Some other pathways synthesizing these precursors, e.g. via oxaloacetate, are assumed to be negligible since even in the mycelium of the lower producing strain increased activities of phosphoenolpyruvate carboxylase were present.

Acetyl Coenzyme A↗
PubMed1975

[Inducible accumulation of alpha-ketoglutaric acid in cultures of Streptomyces hygroscopicus JA 6599 producing a macrolide antibiotic].

The excessive production of pyruvic and 2-oxoglutaric acid by S. hygroscopicus JA 6599 grown on a medium rich in complex carbon and nitrogen sources was studied. Towards the end of the first day of batch cultivation a maximum level of both keto acids in the medium was observed. By diluting the complete culture with water at 22nd hour, however, a further increase in 2-oxoglutarate concentration was induced and the antibiotic production was slightly stimulated. In diluted cultures the oxygen saturation was found to be distinctly higher than in non-diluted ones and, on the other hand, the mycelial activities of both pyruvate and 2-oxoglutarate decarboxylases were decreased. Since the 2-oxoglutarate level was strongly influenced by inhibitors of glycolysis and of citric acid cycle, it is suggested that the metabolite accumulation in diluted cultures is mainly caused by modifications of the metabolic control of carbohydrate catabolism due to an improved aeration. Furthermore, the macrolide antibiotic A 6599 produced by S. hygroscopicus JA 6599 itself was shown to interfere with the accumulation of 2-oxoglutaric acid.

Anti-Bacterial Agents↗
PubMed1975

[Effect of polyene macrolide antibiotics on normal and cell wall deficient Escherichia coli W1655F+ cells].

The polyene macrolide antibiotics are active against yeast, fungi, and other eukaryotic cells, but are with a few exceptions inactive against bacteria. The resistance of bacteria against these compounds is usually explained by the absence of sterols in their cells, the target sites of polyene antibiotics. However, in our experiments with mycotrienin, nystatin, tetramycin, lucenosmycin, rimocidin, filipin, lagosin, flavofungin, flavomycoin, antibiotic 2814P, antibiotic 5001P, and candicidin it was demonstrated that bacteria may be susceptible to polyene antibiotics, too, if the wall-less stable protoplast type L-form of E. coli W1655F+ is used. The measured growth inhibition concentrations were comparable with those of typical antibacterial antibiotics. Our experiments have shown that the normal rod form and the wall-less L-form of E. coli W1655F+ contain traces of sterols in nearly the same concentration range. This means that the selective sensitivity of the L-form cannot be explained by higher sterol content of these cells in comparison to the resistant normal rod form cells. We assume that the bacterial cell wall is responsible for the resistance of the normal rod form by masking internal target sites.

Anti-Bacterial Agents↗
PubMed1975

Streptovirudins, new antibiotics with antibacterial and antiviral activity. II. Isolation, chemical characterization and biological activity of streptovirudins A1, A2, B1, B2, C1, C2, D1, and D2.

Streptovirudin is a complex of antibiotics isolated from fermentation of a Streptomyces strain. Eight components have been isolated as pure substances, designated as streptovirudins A1, A2, B1, B2, C1, C2, D1, and D2. The streptovirudins are chemically and biologically related to each other and appear to be a new family of antibiotics exhibiting activity against a variety of Gram-positive bacteria, mycobacteria, and various DNA- and RNA-viruses. According to their physico-chemical properties these antibiotics have been classified in series I and II. The streptovirudins of series II (A2, B2, C2, D2) are related to the reported antibiotics tunicamycin, mycospocidin and 24010.

Anti-Bacterial Agents↗
PubMed1975

Streptovirudins, new antibiotics with antibacterial and antiviral activity. I. Culture taxonomy, fermentation and production of streptovirudin complex.

A new antibiotic complex has been isolated from cultures of Streptomyces strain No. JA 10124. On the basis of taxonomic studies, the producing microorganism is described as Streptomyces griseoflavus (Krainsky, 1914) Waksman et Henrici, 1948, subsp. thuringiensis subsp. nov., type strain JA 10124. The antibiotic complex, designated as streptovirudin, was isolated from extracts of both mycelium and culture filtrate. It is a white amorphous material which consists of ten closely related components including streptovirudins A, B, C, D and E. The streptovirudin complex exhibits antibiotic activity against Gram-positive bacteria, mycobacteria, and various DNA- and RNA-viruses.

Administration, Oral↗
PubMed1975

Streptovirudins -- new antibiotics with antiviral activity. The antiviral spectrum and inhibition of Newcastle disease virus in cell cultures.

Streptovirudins are new antibiotics isolated as a mixture of several structurally related compounds from fermentations of Streptomyces griseoflavus (Krainsky) Waksman et Henrici var. thuringensis JA 10124. They possess antiviral activity against RNA and DNA viruses cultivated in chick embryo cells, namely Sindbis, fowl plague, Newcastle disease (NDV), pseudorabies, vaccinia and sheep abortion viruses. The naturally formed streptovirudin complex, in concentrations of 20-2.5 mug/ml inhibited the viral cytopathic effect and caused 100 percent plaque reduction. Mengo, Coxsackie B1-B5, ECHO 30 and 33, and polio (wild and attenuated types 1, 2, and 3) viruses grown in FL cells were not sensitive in the agar-diffusion plaque-inhibition test. The antibiotics failed to show a direct virucidal effect on the NDV virion itself or to influence virus adsorption and penetration processes. Addition of streptovirudin complex during a one-step growth cycle of NDV from 0-4 hours after virus adsorption resulted in complete suppression of virus yield. The antibiotic complex consists of two main groups: I - A1, B1, C1, D1, E1 and II - A2, B2, C2, D2, E2, each of which possess antiviral activity.

Anti-Bacterial Agents↗