Selection of the medium for the simultaneous synthesis of an antibiotic, protease and pigment by a Nocardia fructiferi culture

Using method of mathematical planning of experiment the culture medium ensuring the simultaneous intensive production of ristomycin, protease and violet pigment by Nocardia fructiferi has been worked out.     

Comparative study of the therapeutic effect of the glycopeptide antibiotics eremomycin, vancomycin and ristomycin in a model of antibiotic-associated colitis in golden hamsters]

Experiments with a model of intraperitoneal or intragastric lincomycin-induced fatal colitis indicated that eremomycin, vancomycin and ristomycin administered orally in daily doses of 100, 100 and 200 mg/kg, respectively, for 5 days protected the animals from development of antibiotic-associated colitis (AAC), which was evident from prolongation of their life-span to 10-23 days against 3-9 days in the controls. Eremomycin administered intraperitoneally according to an analogous scheme protected the animals from development of AAC, prevented 45 per cent of the animals from death and prolonged the life-span of the other animals to 15-28 days against 3-9 days in the controls. Vancomycin administered intraperitoneally was somewhat more efficient. Still, unlike eremomycin it had a local irritating effect. The protective effect of ristomycin administered intraperitoneally was much lower than that of vancomycin and eremomycin.     

Action of antibiotics on the growth and metabolic processes of streptomycetes and Nocardia

New experimental data on the effect of novobiocin, ristomycin and nystatin on growth and metabolism of Streptomycetes and Nocardia are presented. The study of the organisms producing other antibiotics showed that they were tens, hundreds and even thousands times more sensitive to the tested biologically active compounds than the organisms producing these compounds. The protein synthesis and antibiotic biosynthesis proved to be most sensitive out of the processes studied. The findings showed that during their evolution the antibiotic-producing organisms have developed definite protective mechanisms which enable them to resist relatively high concentrations of their own metabolites (antibiotics). This ensures them in their struggle for existence.     

Effect of glycerin on the biosynthesis of heliomycin by Streptomyces olivocinereus

Glycerol as the sole carbon source was added to the medium or biosynthesis of heliomycin by Streptomyces olivocinereus and the effect of its concentration on the culture growth and antibiotic production was studied. The culture growth and the amount of the antibiotic synthesized per 1 unit of the fermentation broth were limited by glycerol added in quantities of 0.05 to 1 per cent. Further increasing of the glycerol concentration had no significant effect on the culture growth and antibiotic biosynthesis. The amount of the antibiotic synthesized per 1 unit of the mycelial mass relatively slightly depended on the glycerol concentration. The rate of glycerol consumption by the young 24-hour culture in batch fermentations markedly exceeded that of glycerol consumption by the 48-hour culture. The younger mycelium significantly increased its rate of glycerol consumption when the initial concentration was increased whereas the rate of glycerol consumption by the more mature mycelium did not depend on the initial concentration of the carbon source (within 0.5-2 per cent). The rate of heliomycin biosynthesis practically slightly depended on the initial concentration of glycerol.     

The effect of carbon sources and mononucleotides on the production of extracellular alkaline phosphatase by Bacillus intermedius

The biosynthesis of extracellular alkaline phosphatase in the streptomycin-resistant strains Bacillus intermedius S3-19 and S7 in the presence in the medium of 5'-nucleoside monophosphates and different sources of carbon--glucose, sodium pyruvate, sodium lactate, or glycerol--was studied. It was established that, in the presence of mononucleotides, the content of extracellular alkaline phosphatase in both strains increased; the maximal effect was caused by 5'-AMP at a concentration of 20 micrograms/ml. In medium with a low orthophosphate content, where active biosynthesis of alkaline phosphatase occurred, 1% glucose and 0.5% pyruvate stimulated this process 2.5-4 times, and 2% sodium lactate and sodium pyruvate, on the contrary, inhibited it by 20-40%. Analysis of the dynamics of growth and accumulation of extracellular phosphatase in the presence of different sources of carbon in the medium gives evidence of an interrelationship between the biosynthesis of alkaline phosphatase and carbon metabolism in Bacillus intermedius.     

Comparison of the sensitivity of pathogenic staphylococci isolated in 1974 to certain antibiotics and nitrofuran derivatives]

Sensitivity of 267 strains of pathogenic staphylococci isolated in 1974 was studied with respect to some antibiotics and nitrofuran derivatives by the method of serial dilutions on solid media. Sensitivity to penicillin, oxacillin, olemorphocycline, ristomycin and nitrofuran derivatives (furagin and salafur) was observed in 30.7 +/- 2.8, 61.8 +/-3, 29.2 +/-2.8 and 98.9 +/- 0.8 per cent of the cultures respectively.     

Effect of glucose on the antibiotic activity and antibiotic resistance of Streptomyces peucetius subsp. caesius ATCC 27952-2 and its mutants]

The growth of anthracycline producer Streptomices peucetius subsp. caesius ATCC 27952-2 was inhibited by presence of glucose on complete media, containing alternative carbon sources. Amount of clones not producing antibiotic increased to 80.2 per cent along with elevation of glucose concentration in corn meal medium from 0.1 to 1.0 per cent. Mutants of S. peucetius subsp. caesius ATCC 27952-2 able to grow on complete media with 2 per cent of glucose (glr-mutants) were obtained. Glr-mutants had decreased antibiotic production in comparison with 27952-2 strain. 17 per cent of studied glr-mutants synthesized 1.6-3.1-fold quantities of anthracyclines in comparison with parental strain. Glr-mutants synthesized more biomass, although more slowly utilized glucose than strain 27952-2.     

Comparative study of the antibacterial activity of aminoglycoside antibiotics and their combinations with carbenicillin against Pseudomonas aeruginosa

Antibacterial activity of 7 aminoglycoside antibiotics and combinations of tobramycin or gentamicin with carbenicillin was studied with respect to 33 clinical strains of Ps. aeruginosa. Tobramycin, sisomicin, gentamicin and amicacin showed high levels of antibacterial activity. Tobramycin and sisomicin were 3-4 and 2 times more effective than gentamicin. 100 per cent of the Ps. aeruginosa isolates was sensitive to tobramycin and amicacin. The number of the isolates sensitive to sisomicin and gentamicin amounted to 97 and 94 per cent respectively. The respective numbers for streptomycin and kanamycin were 32 and 11 per cent. No monomycin sensitive isolates were detected. Combination of tobramycin or gentamicin with carbenicillin increased the antibacterial activity of the aminoglycoside antibiotics by 2-16 times and that of carbenicillin by 2-32 times. The synergistic effect of gentamicin or tobramycin with carbenicilin was observed with respect to 50 and 58 per cent of the isolates respectively. No antagonistic effect was detected on the combined use of the antibiotics. The majority of the isolates (96 per cent) were sensitive to combinations of carbenicillin in a concentration of 50 micrograms/ml with tobramycin or gentamicin in concentrations of 0.15 or 0.3 micrograms/ml respectively.     

Action of antibiotic combinations with furacilin on the synthesis of proteins and nucleic acids in intact NAG-vibrio cells]

Furacillin in combination with such antibiotics as tetracycline, levomycetin or neomycin inhibited the synthesis of proteins in the cells of NAG-vibrios. Combination of 8 gamma/ml of furacillin and 0.125 gamma/ml of tetracycline inhibited the protein synthesis by 58.8 per cent, 8 gamma/ml of furacillin and 0.5 gamma/ml of levomycetin inhibited the synthesis by 61 per cent, 8 gamma/ml of furacillin and 4 gamma/ml of neomycin inhibited it by 59.5 per cent. At the same time furacillin alone in concentrations of 16 and 8 gamma/ml inhibited the protein synthesis by 69.1 and 37 per cent respectively, tetracycline alone in doses of 0.25 and 0.125 gamma/ml inhibited it by 51.3 and 34.7 per cent respectively, levomycetin alone in doses of 1 and 0.5 gamma/ml inhibited it by 54.4 and 33.2 per cent, enomycin in doses of 8 and 4 gamma/ml inhibited it by 54.4 and 22.6 per cent respectively. Therefore, when the above antibiotics were used in combination with furacillin the inhibitory effect of the drugs on the protein synthesis was summarized. When furacillin was combined with tetracycline or levomycetin in the above concentrations, the inhibitory effect on RNA synthesis (42 or 32 per cent respectively) was lower than that of furacillin alone (50.5 per cent). When furacillin was used in combination with neomycin, the inhibition of RNA synthesis increased up to 69 per cent. The increase in the inhibitory effect was also noted with respect to the synthesis of DNA. Combination of furacillin with tetracycline, levomycetin or neomhcin decreased the synthesis of DNA by 79.7, 85 or 85.8 per cent respectively as compared to the inhibitory effect of 8 gamma/ml of furacillin equal to 61 per cent.     

Relationship between the quality of the inoculum material and carminomycin biosynthesis by a culture of Actinomadura carminata]

The effect of the inoculum mycelium quality on carminomycin biosynthesis by Actinomadura carminata was studied. The time of the organism growth on the culture medium containing cornsteep liquor continued for 6 hours without losing by the inoculum of its seeding qualities during that period. The mycelium growth in the inoculum was more intensive under conditions of moderate aeration, i.e. 0.98-2.64 mg O2H1-min. Anincrease in the aeration rate up to 18.56 mg O2/1-min resulted in the growth suppression up to 40 per cent. No correlation between the aeration rate during the inoculum growth and the culture capacity for carminomycin biosynthesis and of the content of the complex in active components the fermentation medium were observed, when a 5-10 per cent of inoculum was used.     

The sensitivity to 12 antibiotics of 125 strains of Streptococcus group B isolated in a maternity home

Sensitivity of 125 strains of group B streptococci isolated from newborns, their mothers and personnel in a maternity home was studied with respect to 12 antibiotics: benzylpenicillin, ampicillin, methicillin, cephalotin, erythromycin, lincomycin, levomycetin (chloramphenicol), oxacillin, tetracycline, streptomycin, gentamicin and ristomycin. The method of serial dilutions in a solid medium was applied. All the strains were sensitive to ristomycin and erythromycin. The predominating number of the strains were sensitive to lincomycin, levomycetin and the beta-lactam antibiotics. Strains resistant or moderately resistant to benzylpenicillin, ampicillin, oxacillin, methicillin and cephalotin were detected. The majority of the strains were resistant to streptomycin, tetracycline and gentamicin. Multiple antibiotic resistance with 2-7 determinants was revealed in 11.2 per cent of the strains. The antibiotic sensitivity of the strains isolated from the newborns, their mothers and the personnel in the maternity home was on the whole similar or insignificantly differed.     

Effect of protease inhibitors on albumin secretion in hepatoma cells.

Albumin biosynthesis and secretion have been studied in hepatoma cell cultures. The “in vivo” addition of the protease inhibitors antipain or leupeptin caused a fifty per cent reduction in the secretion of albumin without any effect on the total protein synthesis. Pulse and chase experiments in the absence or presence of protease inhibitors have also shown that these substances decrease markedly the rate of albumin secretion.     

Antibiotic sensitivity of Proteus, Pseudomonas pyocyanea and staphyloccoci isolated from scleroma and ozena patients]

Antibiotic sensitivity of 292 strains of Proteus, 60 strains of Ps, aeruginosa, 309 strains of S. aureus and 88 strains of S. epidermidis isolated from the upper respiratory tract of patients with scleroma and ozena was studied. The cultures of Pr. mirabilis were sensitive to aminoglucosides (54.9-96.2 per cent) and Pr. morganii were sensitive to levomycetin (81.5 per cent) and neomycin (92.6 per cnet). Sensitivity of Pr. vulgaris and Pr. morganii was reliably higher (p less than 0.001) than that of Pr. mirabilis. The strains of Pr. morganii were less sensitive to monomycin (P less than 0.001) and streptomycin (p less than 0.01) as compared to the cultures of other Proteus species tested. The strains of Ps. aeruginosa were sensitive only to gentamicin (90 per cent) and neomycin (81.1 per cent). Most of the strains of S. aureus (85.4-100 per cent) were sensitive to oleadomycin, erythromycin, olemorphocycline, tetraolean, oxacillin, methicillin ceporin, lincomycin, ristomycin, kanamycin, monomycin and gentamicin. Benzylpenicillin (90.8 per cent of the sensitive strains), ampicillin (67.1 per cent), tetracycline (66.7 per cent), levomycetin (68.6 per cent) and streptomycin (38.1 per cent) were less effective. Antibacterial therapy in cases with scleroma and ozena should be directed not only against causative agents of the diseases but also against the microbes developing due to disbacteriosis. Combination of parenteral and local use of the antibiotics in the treatment of chronic clebsiellesis decreased the isolation rate of Proteus and Ps. aeruginosa in the patients.     

Study of the activity of a new glycopeptide antibiotic eremomycin combined with tobramycin against Staphylococci in vitro

Eremomycin is an original natural antibiotic with glycopeptide structure isolated at the Institute of New Antibiotics, the USSR Academy of Medical Sciences. Activity of eremomycin alone or in combination with tobramycin was studied with using 25 clinical strains of staphylococci. 56 and 88 per cent of the strains were respectively resistant to gentamicin and kanamycin, two aminoglycoside antibiotics. All the staphylococcal strains were sensitive to eremomycin in concentrations of 0.12 to 1 microgram/ml. The MIC of tobramycin for 10 (40 per cent) sensitive strains ranged within 0.25-2 micrograms/ml. For 60 per cent of the strains the MIC was equal to or higher than 16 micrograms/ml. When eremomycin was used in combination with tobramycin the antibacterial effect with respect to 17 strains (68 per cent) increased. In 32 per cent of the strains the effect was synergistic and in 36 per cent of the strains it was additive. Indifference and antagonism were detected with respect to 7 (28 per cent) and 1 (4% per cent) strains respectively. No significant difference was shown in manifestation of the synergistic-additive nature of eremomycin and tobramycin interaction with respect to the tobramycin sensitive and resistant strains.     

The influence of carbon sources and mononucleotides on the production of extracellular alkaline phosphatase by bacillus intermedium

The biosynthesis of extracellular alkaline phosphatase in the streptomycin-resistant strainsBacillus intermedius S3-19 and S7 in the presence in the medium of 5’-nucleoside monophosphates and different sources of carbon—glucose, sodium pyruvate, sodium lactate, or glycerol—was studied. It was established that, in the presence of mononucleotides, the content of extracellular alkaline phosphatase in both strains increased; the maximal effect was caused by 5’-AMP at a concentration of 20μg/ml. In medium with a low orthophosphate content, where active biosynthesis of alkaline phosphatase occurred, 1% glucose and 0.5% pyruvate stimulated this process 2.5–4 times, and 2% sodium lactate and sodium pyruvate, on the contrary, inhibited it by 20–40%. Analysis of the dynamics of growth and accumulation of extracellular phosphatase in the presence of different sources of carbon in the medium gives evidence of an interrelationship between the biosynthesis of alkaline phosphatase and carbon metabolism inBacillus intermedius.     

The Carbon Balance of a Legume and the Functional Economy of its Root Nodules

Budgets for carbon and nitrogen in shoot, root, and nodulesof garden pea (Pisum sativum L.) are drawn up for a 9-d intervalin the life cycle, from data on nitrogen fixation, carbon accumulationin dry matter, respiratory output of plant organs, and organicsolute exchange between shoot and nodulated root. Of the carbon gained photosynthetically by the shoot from theatmosphere 26 per cent is incorporated directly into its drymatter, 32 per cent translocated to the nodules, and 42 percent to the supporting root. Of the nodules’ share, 5per cent is consumed in growth, 12 per cent in respiration,and 15 per cent returned to the shoot via the xylem, as aminocompounds generated in nitrogen fixation. Growth and respirationof the root utilize, respectively, 7 and 35 per cent. The respiratory efficiency of a nodulated root in terms of nitrogenfixation (5.9mg C per mg N₂-N fixed) is found to be very similarto that of an uninoculated root assimilating nitrate (6.2 mgC per mg NO₃-N reduced). The nodules require in growth, respiration,and export 4.1 mg C ( 10.3 mg carbohydrate) for each mg N whichthey fix. The nodules consume 3 ml O₂ for every 1 ml N₂ utilized in fixation. In exporting a milligram of fixed nitrogen the nodules requireat least 0.35 ml of water. Almost half of this requirement mightbe met by mass flow into the nodules via the phloem.     

Permeability of an actinomycoma for ristomycin (experimental studies)

In vitro studies showed that ristomycin was the most active against actinomycetes causing actinomycosis as compared to benzylpenicillin, ampicillin, methicillin and lincomycin. The growth of the test microbes was inhibited by ristomycin in concentrations of 61--122 mg/ml. Since ristomycin was the most active against actinomycetes, its levels in the blood, parenchymatous organs, capsule and pus of actinomycomas of 5 rabbits infected wtih actino nycosis in the submaxillary area were determined. In the control healthy rabbit, the ristomycin levels were determined in the blood and organs. Ristomycin was administered intravenously in a single dose of 7000 mg/kg. Its concentrations in the animals were determined in 2.5 hours. The results of the experiments showed that ristomycin penetrated in therapeutic concentrations into the connective tissue capsule of actinomycoma. As for the other antibiotics tested earlier, they failed to penetrate this barrier. In 3 infected rabbits, ristomycin penetrated even the pus contained in actinomycoma. Ristomycin provides therapeutic concentrations in the disease focus and may produce a satisfactory therapeutic effect in treatment of actinomycosis.     

Improved production of alkaline protease from a mutant of alkalophilic Bacillus pantotheneticus using molasses as a substrate

An alkalophilic bacterial isolate identified as Bacillus pantotheneticus, isolated from saline-alkali soils of Avadh region of UP, India, was studied for the production of alkaline protease. The mutant of the isolated species showed 44% improved production over the parent strain. Organic nitrogen sources supported better protease production than the inorganic sources. The production of alkaline protease was (242 U/ml) in the medium containing molasses, which was comparable with molasses and wheat bran (285 U/ml) as carbon and nitrogen sources, respectively. Protease production was best at pH 10 and temperature 30 degrees C. The Km (for casein) was 11 mg/ml and Vmax was 380-microg tyrosine/ml/min. The enzyme was stable between pH 7 and 10.7 and temperature between 30 and 60 degrees C with a pH and temperature optimum at 8.4 and 40 degrees C, respectively. The results indicated that molasses was an optimal substrate for alkaline protease production.     

Selection of the seeding media and the age and quantity of mycelia providing simultaneous biosynthesis of an antibiotic and pigment by the fungus Hypomyces rosellus

The authors observed maximum simultaneous biosynthesis of antibiotic and pigment in the microphilic fungus with using 48-hour seed mycelium having the specific growth rate of 0.008-0.011 h-1 in an amount of 5-7 per cent (v). The Balling 4 degrees wart and Chapek medium with 1 per cent of soybean flower and 1 per cent of corn steep liquor may be used for growing the seed mycelium. No significant effect of the seed medium composition and seed mycelium age on the pigment production was observed.     

Biological properties of sherry yeasts in the presence of antimicrobial preparations

The wine yeasts Cheres were not sensitive to high concentration (500 gamma/ml) of benzylpenicillin, streptomycin, tetracycline, oxytetracycline, chlortetracycline, morphocycline, erythromycin, oleandomycin, monomycin, neomycin, kanamycin, polymyxin, ampicillin, oxacillin, methicillin, ceporin, ristomycin, levomycetin, furadonin and furazolidone. In concentrations of 50 to 500 gamma-ml oleadomycin, chlortetracycline, oxytetracycline, kanamycin and ristomycin inhibited synthesis of the Cheres yeast biomass. Benzylpenicillin, polymyxin, neomycin and ampicillin in concentrations of 50 to 100 gamma/ml had a stimulating effect on the yeast biomass synthesis.