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Biomedical subjects

D Gottlieb

Publications and source records attributed to D Gottlieb.

At least 91 records · Page 5Linked to original sources
PubMed1970

Mechanism of action of the fungicide thiabendazole, 2-(4'-thiazolyl) benzimidazole.

Thiabendazole, 2-(4'-thiazolyl) benzimidazole (TBZ) inhibited the growth of Penicillium atrovenetum at 8 to 10 mug/ml. Oxygen consumption with exogenous glucose was inhibited at 20 mug/ml, but endogenous respiration required more than 100 mug/ml. TBZ inhibited completely the following systems of isolated heart or fungus mitochondria: reduced nicotinamide adenine dinucleotide oxidase, succinic oxidase, reduced nicotinamide adenine dinucleotide-cytochrome c reductase, and succinic-cytochrome c reductase at concentrations of 10, 167, 10, and 0.5 mug/ml, respectively. Cytochrome c oxidase was not inhibited. Antimycin A and sodium azide caused the usual inhibition patterns for both fungus and heart terminal electron transport systems. In the presence of antimycin, the fungicide inhibited completely succinate-dichloro-phenolindophenol reductase and succinate-2, 2-di-p-nitrophenyl-(3, 3-dimethoxy-4, 4-biphenylene-5, 5-diphenylditetrazolium)-reductase at 2 and 4 mug of TBZ per ml, respectively. Coenzyme Q reductase required 15 mug/ml. TBZ reduced the uptake by P. atrovenetum of glucose and amino acids and decreased the synthesis of various cell components. At 120 mug/ml, the incorporation of labeled carbon from amino acids-U-(14)C was decreased: lipid, 73%; nucleic acids, 80%; protein, 80%; and a residual fraction, 89%. TBZ did not inhibit peptide synthesis in a cell-free protein-synthesizing system from Rhizoctonia solani. Probably the primary site of inhibition is the terminal electron transport system and other effects are secondary.

Amino Acids↗
PubMed1970

In vitro protein synthesis and aging in Rhizoctania solani.

A study was made of the ability of cell-free protein synthesis systems from vegetative cells of different age of the fungus Rhizoctonia solani to produce polyphenylalanine. Polyuridylic acid-directed phenylalanine incorporation into peptides decreased linearly with cell age. The 105,000 x g supernatant fluid and ribosomal fractions were equally responsible for the total loss of synthetic activity of the older cells. Initial rates of phenylalanyl-transfer ribonucleic acid (tRNA) synthetase activity decreased with increasing cell age, which accounted for the defect of the supernatant fraction. An accelerated degradation of soluble phenylalanyl-RNA was associated with the ribosomes of the older cells. In vitro systems from cells of different age transferred phenylalanine from phenylalanyl-tRNA to polyphenylalanine at similar rates. Of the 15 specific aminoacyl-tRNA synthetases assayed, 5 increased and 5 decreased in specific activity with increased age; 3 others did not change during aging and 2 were below acceptable detectable levels.

Aging↗
PubMed1970

Age-dependent metabolic differences in peripheral hyphae of Rhizoctonia solani.

Peripheral hyphae were separated from the remaining thallus of Rhizoctonia solani in exponential and stationary phases of growth. The QO(2) in whole cells of peripheral hyphae from young fungal colonies was on the average 2.6 times and the protein content 1.6 times greater than in peripheral hyphae from old fungal colonies. The overall rate of amino acid uptake was less in old than in young fungal colonies. In a polyuridylic acid-polyphenylalanine incorporating system, the two kinds of peripheral hyphae required ribosomes, supernatant fraction, polyuridylic acid, soluble ribonucleic acid, adenosine triphosphate, and pyruvate kinase. The rate of polyphenylalanine synthesis in old fungal colonies was slower than in the young fungal colonies. The ribosomes and supernatant fraction of the young and old fungal colonies were interchangeable and active. The factor responsible for deficient protein synthesis in old fungal colonies appears to be in the soluble fraction of the mycelium.

Age Factors↗
PubMed1969

Preparation of four new antibiotics from a mutant of Streptomyces fradiae.

A mutant of Streptomyces fradiae 3535 incapable of synthesizing the antibiotic neomycin in the absence of added deoxystreptamine, the aminocyclitol subunit of the antibiotic, has been isolated from a culture treated with N-methyl-N'-nitro-N-nitrosoguanidine. The related aminocyclitols streptamine and 2-epistreptamine, both available by chemical synthesis, were incorporated by the mutant strain into four new antibiotics, for which we suggest the names hybrimycins A (isomers 1 and 2, from streptamine) and hybrimycins B (isomers 1 and 2, from 2-epistreptamine). Structures of the new antibiotics were established from the mass spectral, nuclear magnetic resonance, and optical rotatory properties of appropriate derivatives. This method offers a promising approach to the synthesis of other antibiotics.

Anti-Bacterial Agents↗
PubMed1969

Mode of action of lomofungin.

Lomofungin inhibited the growth of some yeasts and mycelial fungi at concentrations between 5 and 10 mug/ml. At such concentrations, there was no decrease in endogenous and exogenous oxygen consumption, and even 50 mug of antibiotic per ml caused only slight decreases. The permeation of the cell membrane was changed so that leakage of ninhydrin-positive substances was reduced, and the uptake of (14)C-labeled glucose, amino acids, uracil, and thymidine was decreased at concentrations as low as 4 mug/ml. Protein synthesis in whole cells of Saccharomyces cerevisiae was reduced 35% at 10 mug/ml. However, the antibiotic did not reduce the incorporation of phenylalanine-U-(14)C into polypeptides with cell-free systems of Rhizoctonia solani and S. cerevisiae. The synthesis of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) was inhibited even at concentrations of lomofungin of 4 mug/ml. Since RNA synthesis was inhibited at lower concentrations and earlier than DNA synthesis, the primary site of action of the antibiotic appears to be the synthesis of RNA.

Amino Acids↗
PubMed1969

Mechanism of action of the antifungal antibiotic pyrrolnitrin.

Pyrrolnitrin at 10 mug/ml inhibited the growth of Saccharomyces cerevisiae, Penicillium atrovenetum, and P. oxalicum. The primary site of action of pyrrolnitrin on S. cerevisiae was the terminal electron transport system between succinate or reduced nicotinamide adenine dinucleotide (NADH) and coenzyme Q. At growth inhibitory concentrations, pyrrolnitrin inhibited endogenous and exogenous respiration immediately after its addition to the system. In mitochondrial preparations, the antibiotic inhibited succinate oxidase, NADH oxidase, succinate-cytochrome c reductase, NADH-cytochrome c reductase, and succinate-coenzyme Q(6) reductase. In addition, pyrrolnitrin inhibited the antimycin-insensitive reduction of dichlorophenolindophenol and of the tetrazolium dye 2,2'-di-p-nitrophenyl-(3,3'-dimethoxy-4,4'-bi-phenylene)5,5'-diphenylditetrazolium. The reduction of another tetrazolium dye, 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazolium chloride, that was antimycin-sensitive, was also inhibited by pyrrolnitrin. The antibiotic had no effect on the activity of cytochrome oxidase, and it did not appear to bind with flavine adenine dinucleotide, the coenzyme of succinic dehydrogenase. In whole cells of S. cerevisiae, pyrrolnitrin inhibited the incorporation of (14)C-glucose into nucleic acids and proteins. It also inhibited the incorporation of (14)C-uracil, (3)H-thymidine, and (14)C-amino acids into ribonucleic acid, deoxyribonucleic acid, and protein, respectively. The in vitro protein synthesis in Rhizoctonia solani and Escherichia coli was not affected by pyrrolnitrin. Pyrrolnitrin also inhibited the uptake of radioactive tracers, but there was no general damage to the cell membranes that would result in an increased leakage of cell metabolites. Apparently, pyrrolnitrin inhibits fungal growth by inhibiting the respiratory electron transport system.

Antifungal Agents↗
PubMed1967

Flavensomycin, an inhibitor of enzyme reactions involving hydrogen transfer.

The antifungal antibiotic flavensomycin inhibited the oxidation of amino acids and of glucose by Penicillium oxalicum. The compound inhibited l-amino acid oxidase (EC 1.4.3.2) activity for l-leucine and l-phenylalanine, and also d-amino acid oxidase (EC 1.4.3.3) in the oxidation for dl-alanine. The addition of flavin adenine dinucleotide, which is a cofactor for this enzyme, antagonized the action of the antibiotic. Glucose oxidase (EC 1.1.3.4) was also inhibited. The antibiotic inhibited the reduced nicotinamide adenine dinucleotide (NADH(2)) cytochrome c reductase (EC 1.6.2.1) as well as the much slower nonenzymatic reduction of this cytochrome by the nucleotide. Reduced cytochrome c was also oxidized nonenzymatically by flavensomycin. The antibiotic completely inhibited the action of rabbit muscle lactic dehydrogenase (EC 1.1.1.27) in promoting the reduction of pyruvate by NADH(2) but only slightly affected the reverse reaction. Alcohol dehydrogenase (EC 1.1.1.1) was also similarly inhibited. Flavensomycin prevented the reduction of nicotinamide adenine dinucleotide phosphate by isocitrate in the presence of isocitrate dehydrogenase (EC 1.1.1.42). The hexokinase (EC 2.7.1.1)-catalyzed phosphorylation of glucose, in which the adenosine triphosphate acts as a phosphate donor, was only slightly affected. Flavensomycin also inhibited the action of yeast lactate dehydrogenase (EC 1.1.2.3) on the reduction of cytochrome c. High concentrations of cytochrome c were antagonistic to this reaction. The results point to an interference with enzymatically controlled hydrogen or electron transfer as the mechanism of the antifungal activity of flavensomycin.

Alanine↗
PubMed1966

Changes in fungi with age. Chemical composition of Rhizoctonia solani and Sclerotium bataticola.

Gottlieb, David (University of Illinois, Urbana), and James L. Van Etten. Changes in fungi with age. I. Chemical composition of Rhizoctonia solani and Sclerotium bataticola. J. Bacteriol. 91:161-168. 1966.-The chemical composition of the mycelium of Rhizoctonia solani and Sclerotium bataticola was determined in cells of various ages. The percentage, per unit of dry weight, of soluble amino nitrogen, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), ergosterol, and protein decreased with age in both fungi. Total lipids and fatty acids increased with age in S. bataticola but remained constant in R. solani. Total carbohydrate increased with age in R. solani and decreased in S. bataticola. Fewer changes with age were observed when the results were calculated in ratio to DNA. There was no change in the ratios of protein, RNA, and soluble amino nitrogen to DNA with age in either fungus, but the ergosterol-DNA ratio decreased. The total lipid-DNA ratio and the total fatty acid-DNA ratio increased with age in both fungi, whereas the total carbohydrate-DNA ratio increased in R. solani but remained constant in S. bataticola. Both fungi contained myristic, palmitic, palmitoleic, stearic, oleic, and linoleic acids. In addition, R. solani contained pentadecanoic acid, and S. bataticola had myristoleic, linolenic, and arachidic acids. No marked change in the fatty acid pattern of S. bataticola was observed with age, whereas in R. solani the percentage of linoleic acid per total fatty acids decreased slightly when oleic acid increased.

Carbohydrates↗
PubMed1966

Changes in fungi with age. II. Respiration and respiratory enzymes of Rhizoctonia solani and Sclerotium bataticola.

Van Etten, James L. (University of Illinois, Urbana), H. Peter Molitoris, and David Gottlieb. Changes in fungi with age. II. Respiration and respiratory enzymes of Rhizoctonia solani and Sclerotium bataticola. J. Bacteriol. 91:169-175. 1966.-The rate of respiration of Rhizoctonia solani and Sclerotium bataticola decreased with age. This decrease in respiratory rate might be produced by a decrease in the specific activity of one or more enzymes involved in carbohydrate metabolism. Specific activities in cell-free extracts were measured for most of the enzymes in the hexose monophosphate shunt, Embden-Meyerhof-Parnas pathway, tricarboxylic acid cycle, and terminal electron-transport system. In addition, glucose oxidase, isocitritase, and malic enzyme were measured. In R. solani, increases in activity with age occurred for hexokinase, alpha-glycerolphosphate dehydrogenase, malic dehydrogenase, and cytochrome oxidase. Decreases occurred for phosphohexokinase, aconitase, nicotinamide adenine dinucleotide-specific isocitric dehydrogenase, reduced nicotinamide adenine dinucleotide oxidase, and at least one of the enzymes between 3-phosphoglycerate and pyruvate. In S. bataticola, increases in activity with age were observed for phosphohexokinase, pyruvic dehydrogenase, fumarase, malic dehydrogenase, and malic enzyme, whereas none of the enzymes decreased. The specific activities of the remaining enzymes did not change with age in either fungus.

Carbohydrate Metabolism↗
PubMed1966

Sterols and the sensitivity of Pythium species to filipin.

Schlosser, Eckart (University of Illinois, Urbana), and David Gottlieb. Sterols and the sensitivity of Pythium species to filipin. J. Bacteriol. 91:1080-1084. 1966.-The growth of several Pythium species was not affected by filipin. No leakage of inorganic phosphate was observed after treatment with the antibiotic. No sterol could be detected in 1 g (dry weight) of mycelium. Thus, the insensitivity of these fungi to the antibiotic may be explained by the lack of sterols, the postulated reaction site for filipin in the cell membrane. Though not capable of synthesizing sterols, Pythium species can incorporate exogeneous sterols, which renders them sensitive to filipin; such treatment causes a lag in growth and leakage of inorganic phosphate. The leakage after filipin treatment is indirect evidence that the sterols have been incorporated into the cell membrane. Induced sensitivity to filipin was reversible; it was lost when the sterols were diluted out by one transfer through a medium free from sterols. The hypothesis that the primary site of interaction of filipin is the sterol located in the cell membrane was strengthened by these studies. The experiments further demonstrated a change in sensitivity of a fungus to a toxic agent due to nutritional conditions.

Anti-Bacterial Agents↗