[Effect of antibiotic resistance on the appearance of mutants in a culture of Streptomyces cremeus subsp. tobramycini producing an aminoglycoside complex]. / Vliianie ustoichivosti k antibiotikam na vozniknovenie mutantov v kul'ture Streptomyces cremeus subsp. tobramycini, obrazuiushchei kompleks aminoglikozidov.

Possible formation of auxotrophs and changing of the antibiotic production property connected with resistance to antibiotics of different modes of action were studied in Streptomyces cremeus subsp. tobramycini producing the nebramycin complex of 2-desoxystreptamine derivatives. Four hundred and five spontaneous and 1800 gamma-radiation induced antibiotic resistant mutants of the culture were studied. The frequency of the auxotrophs was shown to be increasing. Correlation between formation of strains producing monocomponent aminoglycosides and antibiotic resistance was observed. The frequency of mutants with preferable synthesis of the tobramycin component among strr-, rifr- and rubr-mutants was 3--10 times higher than among the sensitive portion of the population when total selection was used. Therefore, the spontaneous mutation of antibiotic resistance is selective with respect to both isolation of auxotrophs and strains producing separate aminoglycoside antibiotics.

[Mutagenesis in Streptomycete cultures exposed to bleomycin]. / Mutagenez v kul'turakh streptomitsetov pri deistvii bleomitsina.

Mutagenic properties of bleomycin, an antitumor antibiotic were studied with respect to 2 species of streptomycetes producing practically important antibiotics. A multifold increase in the frequency of prototrophic revertants among the survivors of strains His- and Met- of Actinomadura carminata exposed to bleomycin was observed. Bleomycin was effective in induction of various morphological mutants, and auxotrophs at a high survival rate of the spores of Str. cremeus var. tobramycini, a tobramycin-producing organism. It was shown with the method of subsequent mutagenesis that the efficacy of induction of morphological and auxotrophic mutants in germinating spores of Actinomadura carminata, a carminomycin-producing organism by bleomycin in a concentration of 100 micrograms/ml and an exposure time of 5 minutes was much higher that in the latent spores. The mutagenic effect of bleomycin is comparable with that of ionizing radiation.

[Action of acridine dyes on antibiotic, pigment and aerial mycelium formation in streptomycete producers of multicomponent antibiotics]. / Deistvie akridinovykh krasitelei na obrazovanie antibiotika, pigmenta i vozdushnogo mitseliia u streptomitsetov--prudutsentov mnogokomponentnykh antibiotikov.

The ability of 5 streptomycetous species synthesizing multicomponent antibiotic to produce the antibiotic and water-soluble pigment and to form the aerial mycelium in the presence of acridine dyes was studied. It was found that the character of the produced complex changed, when acridine dyes were added to the medium under conditions not affecting the culture growth and the temperature was elevated. Colonies deficient with respect to formation of the aerial mycelium and with changed pigment and antibiotic production were detected in the monospore cultures of the streptomycetes treated with acridine dyes, when the spore survival was equal to 100 percent, the frequency of the colonies being about 40 per cent.

[Obtaining a productive strain of Streptoverticillium griseocarneum var. bleomycini that yields the new antineoplastic antibiotic, bleomycetin]. / Poluchenie produktivnogo shtamma Streptoverticillium griseocarneum var. bleomycini, obrazuiushchego novyi protivoopukholevyi antibiotik bleomitsetin.

Selection of the organism producing bleomycin, a multicomponent antitumor antibiotic, was performed. The aim was the selection of a more active strain with preferable synthesis of component A5 (bleomycetin) of the bleomycin complex. Optimal variants of the conditions for mutagensis with UV light and gamma-rays in step-wise selection of the active strain were determined and a possibility of selecting analog-resistant mutants with the use of structural analogs of the metabolites participating in synthesis of the bleomycin molecule was studied. A mutant analog-resistant strain capable of supersynthesis of bleomycin A5 (bleomycetin) was selected, the biosynthetic capacity of Streptoverticillum griseocarneum var. bleomycini being increased at least 19 times.

[Obtaining mutants that yield tobramycin in a culture of the producer of a complex of aminoglycoside antibiotics, Streptomyces cremeus var. tobramycini var. nov. 2242]. / Poluchenie mutantov, obrazuiushchikh tobramitsin, v kul'ture produtsenta kompleksa aminoglikozidnykh antibiotikov Streptomyces cremeus var. tobramycini var. nov. 2242.

The organism producing an aminoglycoside antibiotic complex was subjected to selection with a purpose of obtaining a strain producing tobramycin. Spontaneous and gamma-radiation-induced variation of the strains obtained as a result of a step-wise selection of the tobramycin-producing organism was studied. Correlation between the antibiotic activity levels and morphological features of these strains was shown. 8 physiological groups of mutants were differentiated and characterized as dependent on the ratio of the components in the aminoglycoside antibiotic complex produced by them. A highly productive strain 3406 was selected. The level of tobramycin synthesis by this strain is 10 times higher than that of the initial culture.

[Selection of active strains of Actinomadura carminata, the producer of carminomycin]. / Selektsiia aktivnykh shtammov Actinomadura carcminata--produtsenta karminomitsina.

The method of selecting active strains among a definite group of analogue-resistant mutants was used on the basis of studying the dependence of the carminomycin-producing organism growth and the antibiotic synthesis level on some metabolites. As a result, gamma-ray induced mutants 4 times more active than the parent strains were obtained.

Auxotrophic mutants in the selection of the rubomycin producer, Actinomyces coeruleorubidus. / Auksotropnye mutanty v selektsii produtsenta rubomitsina----Actinomyces coeruleorubidus.

A total of 351 auxotrophic mutants with different antibiotic activity, including several mutants with activity higher than that of the parent prototrophic strains were obtained under the effect of gamma-rays from 3 prototrophic strains of Act. coeruleorubidus. It was shown that most of the auxotrophic mutants did not preserve the property of biochemical insufficiency on passages on complete media. A mutant strain 1059-32 with activity 2 times higher than that of the prototrophic strain 2-39 and the parent auxotrophic culture was obtained from the revertants. Requirements in 29 growth factors including 17 amino acids, 4 nitrous bases, 8 vitamins and coenzymes were determined in 46 stable auxotrophic mutants isolated. The effect of the specific and non-specific growth factors on the culture antibiotic production was studied.

[Spontaneous and induced variability in Actinomyces rubiginosohelvolus, a new producer of the antibiotic rubomycin]. / Spontannaia i indutsirovannaia izmenchivost' Actinomyces rubiginosohelvolus--novogo produtsenta antibiotika rubomitsina.

Mutants possessing 3 times higher activity as compared to the initial culture were obtained as a result of selection of active variants of Act. rubiginosonelvolus, a new organism producing rubomycin against the background of variation induced by N-methyl-N1-nitro-N-nitrozoguinidine, diethylsulphate and their combinations. Further selection among the mutants stable to 6-mercaptopurine and riboflavine resulted in obtaining an active culture No. 3912 at least 7 times more active with respect to rubomycin production than the initial soil culture.