Influence of the culture medium on the production of iturin A by Bacillus subtilis

The production of iturin A by Bacillus subtilis was studied with respect to the composition of the culture medium. Increasing phosphate concentrations did not modify the antibiotic yield. Fructose, sucrose and mannitol were better carbon sources than glucose for antibiotic production. The nature of the nitrogen source was an important factor in the production of antibiotic. Among the amino acids which are components of iturin A, L-asparagine was the best substrate for the biosynthesis of iturin A; L-glutamine and L-serine were rather poor substrates while L-proline and D-tyrosine gave no antibiotic. Ammonium salts permitted good synthesis of antibiotic but the addition of calcium ions to the culture medium inhibited the excretion of antibiotic from the cells.     

Effect of mutagenic factors on the variability of cultures of Actinomyces griseus--preducer of the antibiotic grisin

The study of the lethal and mutagenic effect of ethylenimine, nitrozoguanidine, nitrozomethylurea and nitrozoethylurea on Act. griseus Krainsky 15, producing grisin, an antibiotic widely used in agriculture as a stimulator of domestic animal growth showed that induction of mutants with increased antibiotic production levels was most favourable under the effect of ethylenimine. The above mutagens were highly active with respect to induction of morphological mutants. No clear correlation between the colony morphology and antibiotic production property was observed. However, it was noted that the dwarf colonies had a significantly decreased antibiotic activity.     

Stability of the antibiotic formation trait of the tobramycin producer Streptomyces cremeus subsp. tobramycini

The stability of the tobramycin-producing organism was studied by the property of the antibiotic production. The organism was stored under conditions of different exposures to light and subculture on slants. The culture was also subjected to long-term storage with various methods. The organism was stable in preserving its antibiotic activity for 1.5 months when stored on the Gauze organic agar No. 2. Subcultures of the organism on this medium provided preservation of the antibiotic activity throughout 4 passages. The culture storage on millet provided preservation of the antibiotic activity for 6 months.     

Effect of protoplasting on antibiotic activity and resistance in the strain Streptomyces hygroscopicus 155]

The influence of protoplasting and protoplast regeneration in the presence of polyethylene glycol on antibiotic activity, components of antibiotic complexes and antibiotic resistance in Streptomyces hygroscopicus 155 was studied. It was shown that the protoplasting and protoplast regeneration influenced the antibiotic activity. The protoplast fusion resulted in increased isolation of variants with higher antibiotic activity. The processes also affected the components of the antibiotic complexes but had no effect on the strain resistance to some antibiotics.     

Production of the Antibiotic Phenazine-1-Carboxylic Acid by Fluorescent Pseudomonas Species in the Rhizosphere of Wheat

Pseudomonas fluorescens 2-79 and P. aureofaciens 30-84 produce the antibiotic phenazine-1-carboxylic acid and suppress take-all, an important root disease of wheat caused by Gaeumannomyces graminis var. tritici. To determine whether the antibiotic is produced in situ, wheat seeds were treated with strain 2-79 or 30-84 or with phenazine-nonproducing mutants or were left untreated and then were sown in natural or steamed soil in the field or growth chamber. The antibiotic was isolated only from roots of wheat colonized by strain 2-79 or 30-84 in both growth chamber and field studies. No antibiotic was recovered from the roots of seedlings grown from seeds treated with phenazine-nonproducing mutants or left untreated. In natural soils, comparable amounts of antibiotic (27 to 43 ng/g of root with adhering soil) were recovered from roots colonized by strain 2-79 whether or not the pathogen was present. Roots of plants grown in steamed soil yielded larger bacterial populations and more antibiotic than roots from natural soils. In steamed and natural soils, roots from which the antibiotic was recovered had significantly less disease than roots with no antibiotic, indicating that suppression of take-all is related directly to the presence of the antibiotic in the rhizosphere.     

Rifampicin action on the ultrastructure of E. coli cells]

The ultrastructure of Coli bacteria exposed to rifampicin was studied. Dependence of the level of the ultrastructural changes on the antibiotic concentration and the time of incubation with the antibiotic was shown. After exclusion of the antibiotic from the medium the organism growth with normal ultrastructure was observed.     

Cytogenetic effect of the antineoplastic anthracycline antibiotic 4'-epidoxorubicin

Cytogenetic action of 4'-epidoxorubicin (farmorubicin), an antitumor antibiotic was studied with using rat bone marrow cells. It was shown that after intraperitoneal administration the antibiotic increased the number of the aberrant metaphases when the dose was not lower than that equivalent to 1/30 of the LD50. The number of the aberrant metaphases increased with increasing of the antibiotic dose. The maximum number of the cells with impaired chromosomal apparatus was observed 6 hours after the antibiotic administration. In 72 hours it decreased to the level of spontaneous mutations in myelocariocytes. Cytogenetic activity of 4'-epidoxorubicin was comparable to that of doxorubicin (adriablastin) widely used in medical practice.     

Initiation of antibiotic production by the stringent response of Bacillus subtilis Marburg

Bacillus subtilis Marburg was found to produce an appreciable amount of an antibiotic in a synthetic medium. Antibiotic activity was produced in parallel with cell growth, and production stopped at the end of exponential growth. When the synthetic medium was supplemented with a small amount of Casamino acids, however, antibiotic was made only at the end of growth and in lesser amounts. The ability of cells to produce the antibiotic increased when stringent (rel+ = wild-type) cells underwent a partial stringent response. These conditions also initiated extensive sporulation. An isogenic relaxed (rel) strain produced little antibiotic activity, which decreased under partial amino acid deprivation. In rel+ cells, the addition of a low concentration of chloramphenicol, which reduces ppGpp synthesis, also reduced antibiotic synthesis in both normal and amino acid-starved bacteria, without appreciably affecting their growth rate. Guanosine starvation of a gua mutant initiated sporulation, but decreased antibiotic production. The results show that the stringent response initiates both sporulation (differentiation) and antibiotic production (secondary metabolism), but by different mechanisms. It appears that sporulation results from a decrease of GTP, whereas antibiotic synthesis results from a different effect of the stringent response.     

Experimental data on the penetration of gentamicin into the media of the eye]

Penetration of Soviet gentamicin into the humor of the anterior chamber and vitreous body of the eye with aseptic inflammation was studied after the antibiotic administration by various routed, i.e. instillations of 8 per cent antibiotic solution and 8 per cent antibiotic solution methylcellulose into the conjunctival sac, injections of 20 mg of gentamicin subconjunctivally and retrobulbarly, injections of gentamicin intramuscularly in doses of 0.6 mg/kg. The studies showed that gentamicin penetrated into the humor of the anterior chamber and vitreous body of the eye after all the administration routes mentioned above in concentrations sufficient for the antibiotic antimicrobial effect and persisted in the eye media for prolong periods of time (24--48 hours). The highest concentrations of the antibiotic in the tumor of the anterior chamber were achieved after its administration subconjunctivally or after instillation of its 8 per cent on methylcellulose, while in the vitreous body its highest concentrations were achieved after injections subconjunctively, retrobulbarly or intramuscularly. Instillations of gentamicin solution on methylcellulose provided higher and more persistant concentrations of the antibiotic in the humor as compared to instillations of its aqueous solutions. Retrobulbar injections of gentamicin had no advantages as compared to subconjunctival administration with respect to providing higher concentrations of the antibiotic in the eye media.     

Synergy effects of the antibiotics gentamicin and the essential oil of Croton zehntneri

The leaves of Croton zehntneri Pax et Hoffm (Euphorbiaceae) were subjected to hydrodistillation, and the essential oil extracted was examined with respect to antibacterial and antibiotic modifying activity by gaseous contact. The gaseous component of the oil inhibited the bacterial growth of Staphylococcus aureus and Pseudomonas aeruginosa with a MID of 0.5 and<1 mg/l air, respectively. The activity of the antibiotic gentamicin was increased by 42,8% against P. aeruginosa after contact with the gaseous component, showing that this oil influences the activity of the antibiotic and may be used as an adjuvant in the antibiotic therapy of respiratory tract bacterial pathogens.     

Effects of nutrients on the production of AK-111-81 macrolide antibiotic by Streptomyces hygroscopicus

The influence of different carbon and nitrogen sources on the production of AK-111-81 nonpolyenic macrolide antibiotic by Streptomyces hygroscopicus 111-81 was studied. Substitution of glucose with lactose or glycerol significantly affected maximal antibiotic AK-111-81 productivity as the growth rate was close to that of the basal fermentation medium. Addition of ammonium succinate to the fermentation medium markedly increased the antibiotic productivity as the growth rate was low. Divalent ions as Mn2+, Cu2+, Fe2+ stimulated AK-111-81 antibiotic biosynthesis. These results allow us to develop a new fermentation medium showing 6-fold increase of AK-111-81 antibiotic formation compared with the basal fermentation medium.     

抗生素的使用情况调查及细菌耐药性分析

目的:分析我院的抗生素的使用频率以及细菌耐药率的变化,为规范临床用药提供参考资料。方法:采用回顾性分析的方法对我院2009年3月-2013年3月收治的8000例住院患者的抗生素使用情况进行调查,并对我院临床上常见革兰阴性菌和阳性菌的耐药率变化进行比较,分析抗生素的使用频率与细菌耐药率变化之间的关系。结果:临床上抗生素的使用频率最大的是β-内酰胺酶抑制剂以及头孢菌素类。金葡菌对环丙沙星的耐药率与青霉素类抗生素的DDDs呈正相关,大肠埃希菌对亚胺培南的耐药率与头孢菌素类抗生素的DDDs呈负相关。结论:抗生素的用药频率与病原菌对抗生素的耐药率有相关性,并且,单一的抗生素并不能引起病原菌的耐药性,而会同时影响其他类型的抗生素的耐药情况。     

Isolation and physicochemical study of the components of the new antibacterial antibiotic 2562

An antibacterial antibiotic complex consisting of 2 components designated as 2562 A and 2562 B is produced by Streptomyces griseovarabilis. The antibiotic was isolated from the mycelium and purified chromatographically on a column with aqueous silicic acid. The study of the components showed that component 2562 A was chlorbiocin, while component 2562 B differed from the known antibiotics of this group. Physicochemical assays demonstrated that component 2562 B differed from chlorbiocin by the absence of the methyl group in pyrrol, which is probably attached to sugar at beta-position. It was found that component 2562 B is a new representative of the antibiotic cumero-glycoside group.     

Biological characteristics of spectinomycin-resistant strains of the tularemia pathogen

Sensitivity of 2 subspecies of the tularemia causative agent to spectinomycin, an aminoglycoside antibiotic, was studied in vitro. The MIC of the antibiotic with respect to strains 503/847 and Schu was 40 micrograms/ml and with respect to strain A-Cole 20 micrograms/ml. The frequency of spontaneous spectinomycin resistant mutants was low. The mutants grown on a medium containing spectinomycin in a concentration of 100 micrograms/ml were highly resistant to the antibiotic (at least 10000 micrograms/ml). By the main biological properties and virulence the spectinomycin resistant mutants did not differ from the initial strains.     

Experimental study of the pharmacokinetics of an amphotericin B derivative

Absorption, distribution and excretion of a new water soluble derivative of amphotericin B (NWSDA) were studied after its administration by different routes. After the antibiotic intravenous administration the therapeutic concentrations in blood, organs and urine were shown to remain for prolonged periods. The likely sites of NWSDA deposition were detected with microbiological and radionuclide methods. The most prolonged periods of antibiotic preservation were stated in the renal cortex, spleen and lungs. The ways of NWSDA excretion were studied in operated animals. Only 3.5 per cent of the antibiotic was excreted with urine and bile for 24 hours. The pharmacokinetic parameters of NWSDA after its intravenous administration were estimated. The bioavailability of the antibiotic after its intramuscular and oral administration was found to be low.     

The bactericidal action of streptomycin: membrane permeabilization caused by the insertion of mistranslated proteins into the cytoplasmic membrane of Escherichia coli and subsequent caging of the antibiotic inside the cells due to degradation of these proteins.

The mechanism by which the aminoglycoside antibiotic streptomycin permeabilizes the cytoplasmic membrane of Escherichia coli cells was reinvestigated. For this purpose, the extent of streptomycin-induced K+ loss from cells growing at low external K+ concentrations was taken as a measure of membrane permeabilization. Experiments with different K(+)-uptake mutants showed that the antibiotic specifically increased the passive permeability of the cell membrane to K+ and other ions. These permeability changes were small and the membrane potential of the treated cells remained high. The membrane permeabilization was not due to a direct interaction of the antibiotic with the cell membrane, since cells that carry an rpsL mutation and synthesize proteins in a streptomycin-insensitive way did not lose K+ after the addition of the antibiotic. Due to misreading and premature termination of translation the cells synthesized aberrant proteins under the conditions where membrane permeabilization occurred. Two conditions are described under which the cells both degraded these mistranslated proteins rapidly and reaccumulated K+, lending support to the hypothesis that membrane permeabilization is due to the presence of the mistranslated proteins in the cell membrane. Evidence is presented that the irreversibility of (dihydro)streptomycin uptake by cells washed free from the antibiotic might also be due to rapid degradation of the mistranslated proteins, leading to 'caging' of the antibiotic inside the cells.     

Computer analysis of the spatial structure of the amphotericin channel

Energy of Amphotericin B cholesterol complex in a membrane was calculated by the method of atom--atomic potentials. The complex is shown to have two stable states. One of them is stabilized by electrostatic interactions between charged groups of neighbouring antibiotic molecules due to a decline of the molecules to the pore radius. Another state with radial orientation of antibiotic molecules and smaller pore diameter is stabilized mainly by van-der-Waals forces. A conclusion is made that transitions between open and closed states may result from small shifts and turn of all the antibiotic molecules in the complex.     

Role of the functional groups of the sibiromycin molecule in DNA binding]

Biological activity of 2 derivatives of sibiromycin, an antibiotic close by its chemical structure to antramycin and their capacity for formation of complexes with DNA was studied. Anhydrosibiromycin like sibiromycin formed a complex with DNA. The antibiotic increased the DNA melting point but to a less extent than sibiromycin. Anhydrosibiromycin had a low activity in the system of DNA-dependent RNA-polymerase. The low biological activity of anhydrosibiromycin must be due to instability of the antibiotic complex with DNA. Methyl ether of sibiromycin by the phenol hydroxyl, the other derivative of sibiromycin had no biological activity and did not interact with DNA. On the basis of experimental data it was suggested that definite functional groups of the sibiromycin participated in DNA binding.     

Localization of the menaquinone-0 alkylating enzyme in the smooth reticulum of chicken liver microsomes

The effects of the aminoglycoside antibiotic paromomycin on the fidelity of translation of the synthetic template poly(U), and two natural mRNAs (rabbit globin mRNA and Brome Mosaic virus RNA), were examined in an mRNA-dependent cell-free system from the yeast Saccharomyces cerevisiae. At antibiotic concentrations that did not inhibit translation (100 microM) optimal mistranslation of all three templates was observed, with the effects declining at higher antibiotic concentrations. Synthesis of the opal termination read-through protein of rabbit beta-globin mRNA was induced by paromomycin, but only in lysates prepared from a [psi+] strain of yeast. The antibiotic did not induce detectable levels of either ochre or amber read-through, but did induce general misreading of Brome Mosaic virus RNA to the same degree in both [psi+] and [psi-] lysates. This misreading was enhanced by addition of the polyamine spermidine.     

Characterization of the process for the biosynthesis of the actaplanin complex by Actinoplanes missouriensis

The production of the antibiotic actaplanin by Actinoplanes missouriensis was characterized in a high yielding process. The data generated, indicate that the antibiotic is synthesized during a period of declining cell mass as estimated by dry weight and viability. Further study demonstrated that the producing culture binds actaplanin and is inhibited by the antibiotic in the soluble form.