[Mutagenic effect of mitomycin C on different strains of oleandomycin producer Streptomyces antibioticus]. / Mutagennoe deistvie mitomitsina C na raznye shtammy produtsenta oleandomitsina Streptomyces antibioticus.

Mitomycin C, a DNA-tropic antibiotic, was shown to have a lethal effect on spore sprouts of two strains of Streptomyces antibioticus, an organism producing oleandomycin. When the time of exposure to the antibiotic increased there was an almost equal decrease in the survival rate. The mutagen action on the morphological variation and antibiotic production of the two closely related strains were diverse due to their genetic differences. The strain isolated after the culture treatment with a chemical mutagen and subjected to a more prolonged maintaining selection showed lower variation with respect to its colony morphology. The other strain isolated after treatment of the culture with high concentrations of its own antibiotic showed lower variation with respect to its antibiotic production property. The shift in the antibiotic production in the direction of the low active variants was characteristic of the both highly productive strains.

[Toxic action of the polyene antibiotic levorin on the superproducer Streptomyces levoris]. / Tokischeskoe deistvie polienovogo antibiotika levorina na superprodutsent Streptomyces levoris.

Along with an increase in the activity of a superproductive strain of Str. levoris there was observed in its population an increase in the number of low active cells sensitive to high concentrations of the own antibiotic. Levorin had an especially high toxic action on viability and antibiotic activity of the low productive strain 78/19 as compared to the highly productive strain 78/72. Resistance of the levorin-producing organism to its own antibiotic was associated with composition and properties of the cytoplasmic membrane. Acridine orange had no effect on survival and morphological variation of the strains studied. It had either no effect on the antibiotic production by the low active strain 78/19. However, under the effect of the dye there was induced marked variation in the highly productive strain 78/72 with respect to the antibiotic production property: decreasing of the population activity due to elimination of highly productive variants and accumulation of low productive variants. The data suggested the presence of plasmid genes in the levorin-producing organism determining biosynthesis of the antibiotic and resistance to it.

[Intergeneric hydridization of the actinomycetes Streptoverticillium mycoheptinicum and Streptomyces coelicolor]. / Mezhrodovaia gibridizatsiia aktinomitsetov Streptoverticillium mycoheptinicum i Streptomyces coelicolor.

Intergeneric crossing of the actinomycetes Streptoverticillium mycoheptinicum and Streptomyces coelicolor yielded recombinants which were mostly nonviable and unstable despite a relatively high frequency (10(-2)-10(-4)) at which their colonies appeared. The rare viable and stable recombinants were prototrophs. The structure of antibiotics in the hybrid cell may be modified as follows from the differences in the antibiotic activity of the LIA-973 hybrid and the parent strains.

[Auxotrophic mutants of the producer of the antibiotic mycoheptin Streptoverticillium mycoheptinicum]. / Auksotrofnye mutanty produtsenta antibiotika mikogeptina Streptoverticillium mycoheptinicum.

The lethal and mutagenic effects of N-nitrozo-N-methyl biuret (NMB), N-nitrozo-N-methyl urea (NMU) and UV light on Streptoverticillium mycoheptinicum, strains O883 and 852, were studied. The concentrations of NMB were 0.005, 0.1 and 0.25 per cent, the exposure time was 2, 4 and 6 hours. The concentration of NMU was 1 per cent and the exposure time was 1, 2, 3, 4 and 5 hours. The dose of UV light was 2000 erg/mm2. When the spores of Streptoverticillium mycoheptinicum, strain O883, were treated with NMB, the frequency of auxotrophic mutants increased from 0.63 to 3.4 per cent with an increase of the mutagen concentration from 0.05 to 0.25 per cent and the exposure time from 2 to 6 hours. More than 80 auxotrophic mutants were selected. When Streptoverticillium mycoheptinicum, strain 852, was treated with NMU, the frequency of auxotrophic mutants ranged from 0.5 to 2.4 per cent. Fifty-seven auxotrophic mutants were selected. The majority of the auxotrophic mutants selected with the use of NMB and NMU was unstable. Exposure of Streptoverticillium mycoheptinicum, strains 852, 10/69 Met and 54/100 Lys to UV light resulted in formation of groups of polyauxotrophic mutants.

[Developmental cycle and the cytomorphological characteristics of the oleandomycin producer Streptomyces antibioticus]. / Tsikl razvitiia i tsitomorfologicheskie osobennosti produtsenta oleandomitsina Streptomyces antibioticus.

The developmental cycle and cytomorphological features of the industrial strain OL-1 and its variant 0968 of the oleandomycin-producing organism were studied. Variant 0968 was obtained as a result of exposure of the spores of strain OL-1 to UV light. When grown under submerged conditions in flasks with the rich medium, the strains were characterized by a complete developmental cycle consisting of three generations of the hyphae. Every generation had a tendency for formation of submerged spores. The UV-induced variant differed from the industrial strain by higher levels of the antibiotic accumulation which correlated with higher rates of the spore germination. The strains were characterized by polymorphism of the mycelium and formation of submerged spores during their cultivation which is likely to prolong the antibiotic synthesis from 120 to 216 hours from the inoculation moment. The long-term selection of the oleandomycin-producing organism on the rich medium markedly changed the culture genotype and resulted in significant changes in the developmental cycle under submerged cultivation conditions. The data may be used for the microscopic control of the process of oleandomycin production.

[Morphological and biochemical characteristics of Streptomyces hygroscopicus mutants induced by streptomycin and hygromycin B]. / Morfologo-biokhimicheskaia kharaketristika mutantov Streptomyces hygroscopicus, indutsirovannykh streptomitsinom i gigromitsinon B.

Under the effect of streptomycin and hygromycin B there were obtained morphological mutants of Str. hygroscopicus differing in their capacity for synthesis of the antibiotic and a complex of proteolytic enzymes, as well as their resistance to high concentrations of the antibiotics. The mutation of resistance to the aminoglycosides with preservation of the initial phenotype did not result in significant changes in biosynthesis of hygromycin B and the enzyme. At the same time the antibiotic resistant mutants with changed morphology of the colonies were characterized by different capacity for the biosynthesis of the enzyme and antibiotic. Mutants with high, productivity of hygrolytin, not producing hygromycin B were most valuable. Production of hygromycin B correlated with the culture capacity to form aerial mycelium and spores. On the contrary, synthesis of hygrolytin by Str. hygroscopicus did not depend on the morphological characteristics of the culture: strains active with respect to hygrolytin synthesis were found among both the mutants forming abundant aerial mycelium and those not forming it. The study on the biochemical characteristics of the cultures showed that by the lipid content and fatty acid composition they belonged to the same group.

[Morphological and biochemical characteristics of Streptomyces hygroscopicus mutants obtained under the action of acridine orange and mitomycin C]. / Morfologo-biokhimicheskaia kharakteristika mutantov Streptomyces hygroscopicus, poluchennykh pod deistviem akridina oranzhevogo i mitomitsina C.

The purpose of this work was to study the action of acridine orange and mitomycin C on the production of mutants of Streptomyces hygroscopicus, strain 0681. The mutagen activity of mitomycin C was shown to be high. The vegetative culture grown for 24 hours produced more mutants under the action of mitomycin C than spores did. Both acridine orange and mitomycin C caused the production of mutants in strain 0681. The morphology of colonies in these mutants was modified, the synthesis of hygromycin B was completely or partly blocked, and the composition of fatty acids changed quantitatively and qualitatively. Mutants induced by mitomycin C were highly active in the production of the complex of hygrolytin proteolytic enzymes.

[Action of mitomycin C on the variability of Actinomyces hygroscopicus in forming a proteolytic complex of hygrolytin enzymes and the antibiotic, hygromycin B]. / Deistvie mitomitsina C na izmenchivost' Actinomyces hygroscopicus po obrazovaniiu proteoliticheskogo kompleksa fermentov gigrolitina i antibiotika gigromitsina B.

The lethal and mutagenic effect of mitomycin C in doses of 10 and 15 micrograms/ml on the spores and 24-hour culture of Act. hygroscopicus, strain O878 producing hygrolytin, a proteolytic enzyme and hygromycin B, an antibiotic was studied. It was found that mitomycin C had a high lethal effect on the organism. The lethal effect of the antibiotic depended on the stage of the culture development, mitomycin C dose and exposure time. The 24-hour culture was most sensitive to the effect of mitomycin in a dose of 50 micrograms/ml. Exposure to mitomycin increased the actinomycete variation with respect to the colony morphology and induction of new morphological mutations. Exposure of strain O878 to mitomycin C significantly increased the culture variation with respect to the quantitative features of production of the hygrolytin proteolytic enzyme complex and hygromycin B. The character of the strain induced variation with respect to the features studied was different which indicated the absence of correlation between them. The use of mitomycin C proved to be promising in selection of Act. hygroscopicus with a purpose of increasing the culture proteolytic and antibiotic activity.

[Use of antibiotics in selecting a nystatin producer]. / Ispol'zovanie antibiotikov v selektsii produtsenta nistatina.

The lethal and mutagenic effect of streptomycin and nystatin on Act. noursei, strain 408 producing nystatin was studied. The survival of the spores of strain 408 on the medium with streptomycin decreased with an increase in the antibiotic concentration. Streptomycin had a selective effect on the nystatin-producing organism decreasing the frequency of morphologically changed and low active variants and revealing highly active and antibiotic stable variants. The survival of the spores of strain 408 on the medium with nystatin (20,000 units/ml) amounted to 35 per cent. Nystatin had an inhibitory effect on the organism producing it which was evident from delayed growth and significant modification variation of the colonies, as well as from a marked increase in the number of the variants characterized by low antibiotic production.

[Postradiation effect of caffeine on the producer of mycoheptin, Streptoverticillium mycoheptinicum]. / Postradiatsionnoe vliianie kofeina na produtsent mikogeptina Streptoverticillium mycoheptinicum.

The modifying effect of caffeine on irradiated spores of Streptoverticillium mycoheptinicum, producing mycoheptin was found. Postradiation treatment of the strain O883: spores with caffeine resulted in decreased survival of the spores proportionally to the radiation dose increase and postradiation caffeine treatment. An increase in the frequency of the morphologically changed colonies, as well as the low and highly active variants with respect to mycoheptin production was observed. The effect may be explained by the fact that caffeine possibly inhibited the reparation process in the irradiated spores of the strain tested. The method of postradiation treatment of the spores of the mycoheptin-producing organism with caffeine which provided selection of highly active variants by the antibiotic production with the use of definite doses may be considered promising in selection of actinomycetes.

[Lethal and mutagenic action of N-nitroso-N-methylbiuret on the producers of levorin, amphotericin and mycoheptin]. / Letal'noe i mutagennoe deistvie N-nitrozo-N-metilbiureta na produtsenty levorina, amfoteritsina i mikogeptina.

The lethal and mutagenic effect of N-nitrozo-N-methylbiuret (NMB) on the organisms producing levorin, amphotericin B and mycoheptin was studied. The mutagen effect depended on the dose, culture and physiological state of the spores. NMB had a low mutagenic effect on the levorin-producing organism characterized by high activity and genetic homogenicity with respect to the colony morphology and antibiotic production. As for the organisms producing amphotericin B and mycoheptin characterized by high genetic heterogenicity, significant variation of all the features studied was observed on their exposure to the mutagen. Inspite of diverse reaction of the organisms producing levorin, amphotericin B and mycoheptin to the effect of NMB mutants with increased antibiotic production were obtained from the three cultures. The lethal and mutagenic effect of NMB on the mycoheptin-producing organism depended on the process of the spore DNA replication. The spores during the DNA replication period were least sensitive to the lethal effect of the mutagen and most mutable with the respect to the colony morphology. For selection of highly active and stable strains exposure to NMB of the spores of the mycoheptin-producing organism during replication of DNA proved to be more effective than that of the spores during the lag-phase.

[DNA content in Streptoverticillium mucoheptinicum spores in the period of their germination]. / Soderzhanie DNK v sporakh Streptoverticillium mucoheptinicum v period ikh prorastaniia.

Changes in the DNA content were studied in the spores of Streptoverticillium mycoheptinicum. The content of DNA increased in the spores when they were incubated in a liquid nutrient medium at 28 degrees C for 5 hours. Changes in the DNA content during germination of spores corresponded to individual stages: at the stage of activation, the replication of DNA only commenced; at the stage of initiation, the content of DNA doubled in the majority of spores in the population. The rate of DNA synthesis varied among different spores of the actinomycete.

[Selective action of novobiocin on Act. levoris, the producer of levorin and levoristatin]. / Selektivnoe deistvie novobiotsina na produtsent levorina i levoristatina Act. levoris.

The effect of sodium novobiocin on Act. levoris, strain LIA 0868 producing levorin and levoristatin was studied. High lethal effect of the antibiotic on Act. levoris was found. The effect increased with a rise in the antibiotic concentration in the agar from 2 to 6 lambda/ml. The inhibitory effect of novobiocin on Act, levoris was evident from a marked increase in the number of morphologically changed colonies with a low level of levorin production. The selective effect of novobiocin on the organism producing levorin and levoristatin was evident from selection of variants with high levels of levoristatin production on media containing novobiocin.

[Dependence of the lethal and mutagenic effect of mitomycin C and UV rays on the Streptoverticillium mucoheptinicum spore germination process]. / Zavisimost' letal'nogo i mutagennogo éffekta mitomitsina C i UF-luchei ot protsessa prorastaniia spor Streptoverticillium mucoheptinicum.

The lethal and mutagenic effects of the DNA-tropic antibiotic mithomycin C and UV-light on Streptoverticillium mycoheptinicum during the period of the spore replication were studied. The spores were more stable to the effect of the mutagens during DNA replication after 120 minutes of incubation. The mutagenic activity of mithomycin C and UV-light was closely connected with the quantitative changes in the genetic material of the pores. During DNA replication the rate of the morphological mutants was the highest. With respect to production of mycoheptin the spores were most mutable under the effect of mithomycin C during the period of DNA replication, while under the effect of UV-light they were most mutable at the lag-phase.

[Lipid makeup of the initial and selected strains of Actinomyces levoris and Streptoverticillium mycoheptinicum in the process of antibiotic synthesis]. / Sostav lipidov iskhodnykh i selektsionirovannykh shtammov Actinomyces levoris i Streptoverticillium mycoheptinicum v protsesse sinteza antibiotikov

The study of the lipid composition showed that the rate of the changes in the fatty acid composition of neutral lipids and phospholipids in the selected strains was higher than that in the initial strains. The medium composition had the decisive effect on the fractional and fatty acid spectrum of the mycelium lipids. When the antibiotic-producing organisms were grown on the synthetic medium the phospholipids were the predominating fractions (70--90 per cent of the total lipids), while with the use of organic medium they amounted only to 30--40 per cent. The data were evident of complex correlation between the synthesis of fatty acids and polyenic antibiotics, i.e. levorin and mycoheptin.

[Variability of Act. noursei, the producer of nystatin, under the influence of the separate and combined actions of hydrogen peroxide and UV rays]. / Izmenchivost' Act. noursei--produtsenta nistatina pod vliianiem razdel'nogo i kombinirovannogo desistviia perekisis vodoroda i UF-luchei

The lethal and mutagenic effect of hydrogen dioxide used alone and in combination with UV light on the nystatin-producing strain 408 of Act. noursei was studied. The spore survival decreased with an increase in the hydrogen dioxide concentration and the irradiation dose. When the above mutagens were used in combination the lethality was close to the expected one on the summation effect. Under the effect of hydrogen dioxide and most of its combinations with UV light the morphological variation of strain 408 was close to the natural variation or somewhat lower. This phenomenon was possibly associated with significant lethal effect of hydrogen dioxide on the morphologically changed forms of the strain. Variation of the nystatin-roducing strain with respect to nystatin production increased mainly at the account of higher rate of low active variants especially under combined effect of the mutagens. The lethal and mutagenic effect of the combined use of hydrogen dioxide and UV light on the nystatin-producing organism did not depend on the exposure sequence.

[Action of hygromycin B on the producers of levorin and mycoheptin]. / Deistvie gigromitsina B na produtsenty levorina i mikogeptina

The effect of hygromycin B on survival and variation of the levorin and mycoheptinproducing organisms, i.e. Act levoris, strains 28 and PR-52/67 and streptoverticcium mycoheptincium, strain 44B/I was studied. When added to the agarized medium, hygromycin B had a lethal effect on the above strains. The lethal effect increased with an increase in the concentration from 2.5 80 Units/ml. High modification variation of the colony morphology was observed on media with hygromycin B. At the same time hygromycin B induced morphological and hygromycin-resistant mutants. The variation of the property of the antibiotic production in the above cultures increased under the effect of hygromycinB. The maximum rate of the plus variants was observed at high lethal effects of hygromycin B, when the survival rate of the spores was 10(-3) and 10(-4). An individual reaction of the cultures to hygromycin B was found. Formation of the mutation of resistance to the specific phage in the genome of strain PR of the levorin-producing organism increased its sensitivity to hygromycin and variation of the colony morphology and the property of the antibiotic production.

[Production in an Actinomyces levoris culture under the action of an actinophage specific to it of variants with stable preservation of its resistance to the phage]. / Poluchenie u kul'tury Actinomyces levoris pri vozdeistvii spetsifichnym dlia nee aktinofagom variantov, stoiko sokhraniaiushchikh k nemu ustoichivost'

Act. levoris 28, an organism producing levorin was treated with an actinophage virulent to it. Variants of the organism were isolated from the secondary growth of the culture. As a result of lysogenization with the above phage the variants acquired stability to it which was preserved during the further generations. In the previous experiments carried out by the authors the variants isolated from the secondary growth of the culture after its exposure to the same phage lost their stability to the phage as a result of loosing the prophage by it during the subsequent passages. The phage stable variants did not differ from the initial culture either in the activity of levorin or the levorin composition. The phages found in the initial culture 28, and the virulent mutant were identical with respect to the particles morphology and antigenic properties which confirmed their relation.