Comparative characteristics of some actnomycetes, producers of antifungal antibiotics related to chondamycin]

Three actinomycetous strains designated as LIA-0773, LIA-0783 and LIA-0780 were isolated from various soil samples. The cultures actively inhibited the growth of Trichophyton gipseum and produced a non-polyenic antibiotic of the chondamycin type. The strains were identified with Act. griseochromogenes Fukunaga et. al., 1955. The cultures differed within the species by some morphological, cultural, physiological and antibiotic properties, as well as by the component composition of the antibiotic produced. Thus, strain LIA-0773 had larger spiral sporophores, satisfactorily hydrolized starch and inverted sucrose. The strain inhibited the growth of not only the fungi but also grampositive bacteria and mycobacteria and produced an antibiotic composed of 6 components. Strain LIA-0780 had small sporophores with close spirals and low amilolytic activity. It inhibited only the growth of the fungi and produced a monocomponent antibiotic. Strain LIA-0783 was intermediate. By its biological properties it was closer to strain LIA-0780. The antibiotic produced by it consisted of 6 components, while by its physico-chemical properties the antibiotic was close to that produced by strain LIA-0780. All the 3 actinomycetous cultures were considered as different variants of Act. griseochromogenes Fukunaga et al., 1955.     

Characteristics of diffusion of polyene antibiotic levorin

Studies were performed which provided estimation of the impact of some physico-chemical properties of levorin, a polyene antibiotic, and in particular its multicomponent nature and capacity for isomerization on formation of inhibition zones in assay of the antibiotic activity by the agar diffusion method. It was shown that the levorin complex components markedly differed in the biological activity and diffusion capacity. The diffusive properties of the highly active components A2 and A3 were better. The diffusion rate of isomerized levorin was much lower than that of the initial levorin. To provide better diffusion of the levorin components with low diffusion capacity it was recommended to use a new solution composed of ethanol, glycerol and water at a ratio of 15:25:60.     

New tetraene antibiotic, abkhazomycin]

The cultures of Act. L10-0740 and L10-0772 were isolated from a soil sample. By their morphological and cultural features they were close to Act. badiocolor and differed from the latter by their antibiotic properties. Because of this they were classified as a new variant of Act. badiocolor var. abhasus var. nov. The cultures produced a new tetraen antibiotic, named abkhazomycin. Its physico-chemical properties are presented.     

New antibiotic, parvulomycin, produced by a culture of Actinomyces parvullus var. chromogenes var. nov]

Actinomycete LIA-O784 was isolated from a soil sample. By its morphological and cultural properties the isolate was close to Act. parvullus but differed from it in synthesis of melanoid pygment, thyrosinase, hydrogen sulphide and pronounced antifungal activity. The actinomycete was classified as a new variant and designated as Actinomyces parvullus var. chromogenes var. nov. The culture produced a new polyglycoside antibiotic named parvulomycin. The physico-chemical characteristics of the antibiotic is presented.     

Oleandomycin and its natural and synthetic analogs. II. Structure and properties of oleandomycin B, a new compound of the oleandomycin group

The revealed regularities of mass spectroscopic disintegration of oleandomycin and its derivatives made it possible to determine analytic criteria for identification of compounds related by their structure to oleandomycin. Analysis of the extracts from oleandomycin fermentation broth filtrates on the basis of the selected group of diagnostic ions showed that along with the main antibiotic there formed during the biosynthesis oleandomycin B, a structurally close minor component. The structure of the substance was assigned and its physico-chemical and biological properties were studied.     

Physico-chemical characteristics of the new antitumor antibiotic virenomycin

Virenomycin, a new crystalline antitumor antibiotic was isolated from the mycelium of Streptomyces virens. The antibiotic contained: C 64.87 per cent, H 5.66 per cent, methoxylic groups 9.5 per cent. The melting temperature was 255-260 degrees (dec.), [alpha]20D=-17 (c 0.142, chloroform). Virenomycin had a complex UV spectrum with lambdamax. 245 (677), 265 (453), 275 (542), 287 (507), 395 (222) nm. A chromofor fragment and carbohydrate (C7H14O5) were found in the methanolysis products. Virenomycin was close to antibiotic c B-21085 BY THe physico-chemical properties and differed from it in the character of the UV spectrum and the values of the specific absorption, as well as by the optic rotation in dimethyl sulphoxide and acetic acid.     

Physiochemical properties of LIA-0191 A and B antibiotics

An antifungal antibiotic LIA-0191 was isolated from the mycelium by methanol extraction. It was shown with thin-layer chromatography that it consisted of components A and B. Component A was isolated with collumn chromatography on silica gel, recrystalization from the solvent mixture as a monocomponent crystalline substance. On the basis of the physicochemical and biological properties it was identified with sentacidin. Component B was obtained from preparation LIA-0191 by the method of counter-current distribution and recrystalization from methanol. Comparison of its physico-chemical and biological properties with those of the known purines and pyrimidine pyrrol showed that antibiotic LIA-0191 B is new.     

New species of the genus Nocardia and its antibiotic properties]

A culture of a new species of Nocardia, i.e. N. indigoensis producing an antibiotic close to celicomycins was isolated from a soil sample of Kazakhstan plated on the selective medium with kanamycin. By a number of chemical properties and biological activity the antibiotic differed from celicomycins. Probably it is a new natural substance.     

Enzymatic glycosylation of lincomycin

Lincomycin (1), a glycosidic antibiotic, active against Gram-positive bacteria, was modified enzymatically with the aim of improving its physico-chemical and biological properties. Compound 1 was glycosylated using jack bean alpha-mannosidase to produce 7-O-alpha-D-mannopyranosyl-lincomycin (2).     

Biological properties of clinical staphylococcal strains with a varying number of antibiotic resistance markers]

The study of a number of biological properties of 1881 clinical strains of Staphylococcus showed that in the group of the antibiotic resistant staphylococci there was a tendency for different manifestation of some biological properties depending on the number of the resistance determinants. The staphylococcal strains resistant to 5--7 antibiotics differed from those resistant to a less number of the drugs by greater manifestation of the pathogenicity properties: lecithinase, hyaluronidase and hemolytic activity.     

New heptaene antibiotic, flavomycin, formed by Act. flavus var. geptinicus var. nov]

An actinomycetous culture LIA-0734 was isolated from a soil sample. By its morphologo-cultural properties it was close to Act. flavus and differed from the latter in the sporophores, colour of the substrate mycelium on synthetic media amd markedly pronounced antagonism with respect to yeasts and yeast-like fungi. The culture was classified as Act. flavus var. geptinicus var. nov. The actinomycete produced new aromatic heptaens: flavomycins A and B. Their physico-chemical and biological characteristics and singularity are presented.     

Effect of penicillin on the antigenic properties of serum beta-lipoproteins]

Peculiar characteristics of the antigenic properties of penicillin compounds with heterological and homological beta-lipoproteids of the blood serum were investigated. The beta-lipoproteids isolated from the blood serum of humans (donors) and rabbits were mixed with potassium benzylpenicillin (10000 and 50000 gamma/ml). Twenty seven rabbits were immunized with such compounds and solutions of beta-lipoproteids without addition of the antibiotic. The antisera obtained from the animals were used in the reaction of precipitation and immunoelectrophoresis, the results of which were densitometrized. Some physico-chemical properties of the preparations, such as pH, electrokinetic features were also studied. It was shown that the immunochemical properties of heterological beta-lipoproteids, i.e. precipitation bands changed due to the effect of penicillin. They differed from the control by compactness and contrastness, their amounts decreased, a separate band not identical to that of the control antigen appeared. A separate or intermediate antigen was found in the experiments with serum exhaustion. The peculiarities of the precipitation reaction were confirmed by the immunoelectrophoregrams. These differences were also registered on the densitograms. The compounds of penicillin with homological beta-lipoproteids of the rabbit blood serum induced formation of specific precipitins in the animals. Some physico-chemical properties of beta-lipoproteids also changed under the effect of penicillin.     

The melanoidin-containing preparation MIGI-K from mussels and its characteristics]

The physico-chemical properties of preparation MIGI-K from mussels are given. Some characteristics of melanoidin fractions of MIGI-K are presented, their similarity to standard melanoidin is revealed. The given data on biological activity of the preparation permit to consider MIGI-K as immunomodulator.     

A new pigmented antibiotic from a soil streptomycete

An antibiotic designated Ass was isolated from a soil streptomycete -which showed wide antibacterial activity. The antibiotic was extracted and purified into a yellow powder. Its physico-chemical and antimicrobial properties indicated that it is a novel peptide antibiotic.     

Eremomycin--a new antibiotic of the polycyclic glycopeptide group

Eremomycin is a novel antibacterial antibiotic. It was isolated at the Institute of New Antibiotics, the USSR Academy of Medical Sciences from the culture fluid of actinomycete INA-238. By its physico-chemical and biological properties the antibiotic was classified as belonging to the group of polycyclic glycopeptides. Chemical structure of eremomycin was asserted and it was shown to be a new representative of the group close by its structure to vancomycin and differing from it by the carbohydrate composition and structure of tri-phenoxytriaminotricarboxylic acid. By its anti-bacterial spectrum eremomycin was found to be close to ristomycin and vancomycin. Still, its activity was 2-10 times higher. The antibiotic was several times less toxic than vancomycin. Unlike vancomycin and ristomycin, the novel antibiotic induced no tissue necrosis after its intramuscular administration. The chemotherapeutic indices of eremomycin in treatment of staphylococcal and streptococcal sepsis in albino mice exceeded 10 times those of vancomycin. At present eremomycin is under clinical trials.     

Biosynthesis and the isolation of the new anthracyclin antibiotics, violamycins A, BI, BII and their aglycones]

The conditions of fermentation, isolation and some of the physico-chemical properties of the new anthracycline antibiotics, i. e. viomycin A, BI, BII and their aglycones, produced by a strain of Streptomyces violaceus IMET JA 6844 are described. Violamycin A is mainly a complex of aminoglycosides of epsilon- and dzeta-isorhodomycinone, beta-rhodomycinone and (alpha)2-rhodomycinone. The sugar component is rhodosamine. Violomycin BI is mainly a complex of trisaccharides of the same aglycones mentioned above. The sugar components are rhodosamine, 2-desoxy-L-fucose and rhodinose. Violomycin BII is mainly a rhodosaminyl-2-desoxy-L-fucosyl-derivative of epsilon- and dzeta-isorhodomycinone, beta- and epsilon-rhodomycinone and (alpha)2-rhodomycinone. Violamycin complexes A, BI, BII mainly consist of 6 aglycone components which are similar to the other members of anthracyline antibiotics but can be diferentiated from them by physico-chemical and biological properties. Epsilon- and dzeta-isorhodomycinone, epsilon- and (alpha)2-rhodomycinone and dzeta-rhodomycinone one of the 8 minor components contained in the mixture of the aglycones of the violomycin complex so far has been determined as constituents of an antibiotic.     

Investigation of the antibiotic complex produced by <Emphasis Type="Italic">Lactococcus lactis</Emphasis> subsp. <Emphasis Type="Italic">lactis</Emphasis> 194, Variant K

Phase variation in the culture of the environmental strain Lactococcus lactis subsp. lactis 194 resulted in the formation of two types of colonies differing by 15% in antibiotic activity. The active variant 194-K produced an antibiotic complex with a broad spectrum of antibacterial and antifungal activity. Five components (194-A, B, C, D, and E) were isolated from the complex by solid-phase extraction and thin-layer chromatography. Components 194-A and 194-B were hydrophobic neutral compounds soluble in organic solvents. Component 194-A possessed fungicidal activity, whereas component 194-B exhibited only bactericidal activity. Physicochemical studies of the isolated components 194-A and 194-B revealed that they had no analogs in the Berdy database of biologically active substances (BNPD) and appeared to be novel antibiotics. Component 194-C was a hydrophilic polar compound inhibiting growth of gram-positive and gramnegative bacteria. Component 194-D belonged to peptide antibiotics; it inhibited growth of only gram-positive bacteria and was similar to nisin A in biological properties but differed in electrophoretic mobility and molecular mass.     

Antibiotic and biosurfactant properties of cyclic lipopeptides produced by fluorescent Pseudomonas spp. from the sugar beet rhizosphere

Cyclic lipopeptides (CLPs) with antibiotic and biosurfactant properties are produced by a number of soil bacteria, including fluorescent Pseudomonas spp. To provide new and efficient strains for the biological control of root-pathogenic fungi in agricultural crops, we isolated approximately 600 fluorescent Pseudomonas spp. from two different agricultural soils by using three different growth media. CLP production was observed in a large proportion of the strains (approximately 60%) inhabiting the sandy soil, compared to a low proportion (approximately 6%) in the loamy soil. Chemical structure analysis revealed that all CLPs could be clustered into two major groups, each consisting of four subgroups. The two major groups varied primarily in the number of amino acids in the cyclic peptide moiety, while each of the subgroups could be differentiated by substitutions of specific amino acids in the peptide moiety. Production of specific CLPs could be affiliated with Pseudomonas fluorescens strain groups belonging to biotype I, V, or VI. In vitro analysis using both purified CLPs and whole-cell P. fluorescens preparations demonstrated that all CLPs exhibited strong biosurfactant properties and that some also had antibiotic properties towards root-pathogenic microfungi. The CLP-producing P. fluorescens strains provide a useful resource for selection of biological control agents, whether a single strain or a consortium of strains was used to maximize the synergistic effect of multiple antagonistic traits in the inoculum.     

Effects of cysteine to serine substitutions in the two inter-chain disulfide bonds of insulin

Using site-directed mutagenesis we deleted the two inter-chain disulfide bonds of insulin, separately or both, by substitution of the cysteine residues with serine. Deletion of A20-B19 or both of the two inter-chain disulfide bonds resulted in the complete loss of secretion of the mutant single-chain porcine insulin precursor (PIP) from Saccharomyces cerevisiae cells. Removal of the A7-B7 disulfide bond resulted in a large reduction of secretion, but we could obtain the mutant for analysis of its biological and some physico-chemical properties. The A7-B7 disulfide bond deleted insulin mutant retained only 0.1% receptor-binding activity compared with porcine insulin, and its in vivo biological potency measured by mouse convulsion assay was also very low. We also studied some physico-chemical properties of the mutant using circular dichroism, native polyacrylamide gel electrophoresis and reversed-phase HPLC, which revealed some structural changes of the mutant peptides compared to native insulin. The present study shows that the two inter-chain disulfide bonds are important for efficient in vivo folding/secretion of PIP from yeast, especially the A20-B19 disulfide bond, and that the A7-B7 disulfide bond is crucial for maintaining the native conformation and biological activity of insulin.     

New antibiotically active fluoroglucide from Pseudomonas aurantiaca]

A new metabolite with an antibiotic activity against grampositive bacteria in concentrations of 0.1--1.0 gamma/ml was isolated from the culture fluid of Pseudomonas aurantiaca. The study of its physico-chemical properties showed that it was di-2,4-diacetylfluoroglucylmethan. The conclusion was confirmed by synthetic studies. Di-2,4-diacetylfluoroglucylmethan belongs to the group of the antibiotics, derivatives of fluoroglucin, characteristics metabolites of Pseudomonas aurantiaca.