[Antimicrobial and membranolytic activity of sterically hindered phenols]. / Antimikrobnaia i membranoliticheskaia aktivnost' ékranirovannykh fenolov.

Antimicrobial activity of some complicated space phenols (screened) was studied. The compounds had different activities against grampositive bacteria and were inactive against gramnegative microbes. Di-tertiary butyl derivatives of pyrocatechol and resorcin showed the highest activities. The MICs of such derivatives for the collection strains of Bacillus megaterium, Bacillus subtilis and Staphylococcus aureus were 8 to 30 micrograms/ml and exceeded 6-25 times those of the nonsubstituted analogs. The derivatives of pyrocatechol and resorcin impaired the membrane permeability in susceptible intact cells of B.megaterium and S.aureus 209P and had no effect on the membrane permeability of the Escherichia coli resistant cells. In concentrations up to 200 micrograms/ml the nonsubstituted analogs of pyrocatechol and resorcin did not impair the membrane permeability in the intact cells of the above bacteria. Di-tertiary butyl derivatives of pyrocatechol and resorcin had lytic activity with respect to cytoplasmic membranes (protoplasts) of B.megaterium and had no lytic action on E.coli spheroplasts. The antimicrobial spectrum correlated with the membranotropic properties of the compounds. It was suggested that the target of the antimicrobial action of the screened phenols was the bacterial cell cytoplasmic membrane.

[A conjugate of ristomycin A ristosaminylaglycon-polymyxin B: the spectrum of its antimicrobial action and its membranolytic activity]. / Kon''iugat ristozaminilaglikon ristomitsina A--polimiksin B: spektr antimikrobnogo deistviia i membranoliticheskaia aktivnost'.

Antimicrobial activity of a conjugate based on two antibiotics, i.e. ristomycin A and polymyxin B was studied. The conjugate was shown to have a broad antimicrobial spectrum. In concentrations of 5 to 30 micrograms/ml it inhibited the growth of gram-positive and gram-negative bacteria and in concentrations of 5 to 40 micrograms/ml it inhibited the growth of the pathogenic clinical strains. An insignificant membranolytic action of the conjugate with respect to membranes of the susceptible bacteria and no hemolytic action on human red blood cells were detected.

[The effect of millimeter-band radiation of nonthermal intensity on sensitivity of Staphylococcus to various antibiotics]. / Vliianie millimetrovogo izlucheniia neteplovoi intensivnosti na chuvstvitel'nost' stafilokokka k razlichnym antibiotikam.

The affect of preliminary irradiation of staphylococcus culture by electromagnetic radiation of extremely high frequency (42, 54, 66 + 78 GHz) of nonthermal intensity on the bacteria growth on the media containing various antibiotics is studied. The reliable change in bacteria sensitivity toward 5 antibiotics, mainly having membranotropic properties is observed in the experiments using 14 antibiotics with various mechanisms of action. It has been established that in the presence of subbactericide concentrations of active antibiotics the irradiation could result in both further suppression of bacteria growth and its stimulation. As shown, the development of these effects takes place even in a matter of minutes of preliminary irradiation, and weak changes are observed at further increase of this period up to 60 min.

[Membranolytic activity of gradex]. / Membranoliticheskaia aktivnost' gradeksa.

The membranolytic activity of gradex towards bacterial protoplasts and human erythrocytes has been demonstrated. Dextran shows no such activity. The lytic activity of gradex towards protoplasts is much lower as compared to gramicidin S. The increase in gramicidin S content from 2 to 5% caused no significant changes in the lytic activity of gradex towards protoplasts. The reduced form of gradex nad no hemolytic effect on human erythrocytes up to a concentration of 300 micrograms/ml. However, the non-reduced form of gradex af a concentration of 500 micrograms/ml lysed from 31 to 48% of erythrocytes depending on the antibiotic content in the polymeric matrix.

[Metabolism of alpha-ketoacids in erythromycin biosynthesis in various strains of Saccharopolyspora erythraea]. / Metabolizm al'fa-ketokislot pri biosinteze éritromitsina u razlichnykh shtammov Saccharopolyspora erythraea.

The absence of pyruvate and insignificant levels of alpha-keto-glutarate in the mycelium during the fermentation cycle were characteristic of a highly active erythromycin-producing strain of Saccharopolyspora erythraea. Alpha-keto-glutarate partially excreted to the fermentoffon broth. The activity of pyruvate decarboxylase and alpha-keto-glutarate decarboxylase was detected in the cells during the entire period of the cultivation. The same regularities were observed in the chloramphenicol resistant mutant of the strain. The mycelium of a low productive strain of S.erythraea contained not only alpha-keto-glutarate but also pyruvate and excreted large amounts of keto-acids. By the activity levels of the decarboxylases the low productive strain did not differ from the highly productive one. Propanol did not influence the growth of the low productive strain and the synthesis of erythromycin by it. However, it stimulated accumulation of keto-acids and especially pyruvate in both the mycelium and fermentation broth. Relation between the intensity of keto-acid metabolism and erythromycin biosynthesis is discussed.

[Antimicrobial and membranolytic activities of anti-burn drug fenozan]. / Antimikrobnaia i membranoliticheskaia aktivnost' protivoozhogovogo preparata fenozana.

Fenozan, an anti-burn preparation, was shown to have antimicrobial activity against freshly isolated clinical strains of Staphylococcus aureus and Streptococcus faecalis, as well as against collection strains of the other gram-positive bacteria. The antimicrobial action of the preparation was possibly due to impairment of permeability of the cytoplasmic membranes in the sensitive bacterial cells and their liberation of intracellular low molecular weight compounds to the environment. The membranolytic and minimum inhibitory concentrations of fenozan with respect to the sensitive bacterial cells were one order of magnitude lower than the concentration stabilizing the membranes of animal cells in the treatment of burns. Combination of the antioxidant and antimicrobial properties in fenozan was likely to provide its satisfactory therapeutic effect in the treatment of burn wounds.

[Antimicrobial and hemolytic activities of gradex]. / Antimikrobnaia i gemoliticheskaia aktivnost' gradeksa.

Gradex is a polymer preparation resulting from formation of covalent bonds between the molecules of gramicidin S, a polypeptide antibiotic, and dextran, a polymeric carrier. Antimicrobial and hemolytic activities of gradex were studied. It was shown that the antimicrobial activity of gradex was due to the presence of gramicidin S in its composition. The activity level was lower than that of gramicidin S. It was also found that the gradex reduced form in concentrations up to 300 micrograms/ml had practically no hemolytic effect against human erythrocytes. The reduced form of gradex is promising for development of an artificial ++anti-brucellosis vaccine.

[Action of different types of gramicidin S derivatives on bacterial cells and protoplasts]. / Deistvie razlichnykh tipov proizvodnykh gramitsidina S na kletki i protoplasty bakterii.

The work was concerned with studying the effect of gramicidin S derivatives with modified free amino groups of ornithine residues on bacterial cells and protoplasts. The substitution of the amino groups with neutral or carboxyl-containing groups eliminated or sharply decreased the antibacterial activity of gramicidin S, its binding to the cells, and the ability to change the permeability of the cytoplasmic membranes of the intact cells. However, the neutral derivatives and the derivative with acidic properties showed a considerable lytic activity when they were incubated with the protoplasts of Micrococcus lysodeikticus, Bacillus megaterium and Bacillus subtilis. Hence, these compounds preserved a certain membranotropic level. Those gramicidin S derivatives with modified ornithine amino groups which possessed basic properties were similar to gramicidin S in the antibiotic activity, the modified permeability of the membranes, the ability to bind with the cells, and the lytic action on the protoplasts.

[Optical density changes in bacterial protoplast suspensions exposed to membrane-active antibiotics]. / Izmenenie opticheskoi plotnosti suspenzii bakterial'nykh protoplastov pri deistvii membranoaktivnykh antibiotikov.

The effect of membrane active antibiotics, such as gramicidin S, its derivatives and carbonyl-conjugated pentaens on suspended bacterial protoplasts resulted in lysis of the protoplasts accompanied by a marked decrease in the optical density (OD) of the suspensions. However, when the drug concentrations were lower than those inducing the lysis, an increase in the suspension OD by 10-30 per cent as compared to the control values of the OD was often observed. The increase in the protoplast suspension OD was most pronounced with the use of the drugs with a relatively low lytic activity or under the conditions lowering the lytic activity of the antibiotics. Under such conditions no agglutination of the protoplasts was observed. The comparative estimation of the protoplast diameters by the method of Klenin et al. in the control suspensions of M. lysodeikticus protoplasts and in the suspensions with a stable increase in the OD showed that the OD increase was associated with swelling of the protoplasts: an increase in the suspension OD by approximately 30 per cent corresponded to an increase in the protoplast diameter by approximately 15 per cent. The observed increasing of the suspension OD must be due to the fact that the membrane active antibiotics induced a decrease in the osmotic stability of the protoplasts not sufficient for their lysis.

[Effect of gramicidin S and its derivatives on protoplasts of Bacillus subtilis]. / Deistvie gramitsidina S i ego proizvodnykh na protoplasty Bacillus subtilis.

The lysis of Bacillus subtilis protoplasts by gramicidin S, a membrane active antibiotic, and its derivatives was studied according to free amino groups of the ornithine residue. The initial antibiotic and guanylgramicidin , a positive charge-preserving derivative, had a high lytic activity. Succinylgramicidin , a gramicidin S derivative with acid properties, and carbomoylgramicidin , a neutral derivative, actively lysed B. subtilis protoplasts suspended in 1/15 M phosphate buffer solution with sucrose . No lytic activity of succinylgramicidin was observed with respect to B. subtilis protoplasts suspended in an aqueous solution of sucrose. Comparative study on the sensitivity of the protoplasts of Micrococcus lysodeikticus, B. megaterium and B. subtilis to the lytic action of gramicidin S and its derivatives showed in the main a similar character of their interaction with the membranes of the protoplasts of the taxonomically close species (B. megaterium and B. subtilis). It is likely that the specificity of the action of the above substances on the protoplasts of M. lysodeikticus, i. e. a complicated character of the dependence of the lytic action of gramicidin S on its concentration, manifestation of the lytic activity of the neutral and acid derivatives in the presence of phosphates or other salts and in sucrose aqueous solution was mainly defined by the properties of the micrococcal membranes.

[Comparison of the lytic effect of gramicidin S and its derivatives on Bacillus megaterium and Micrococcus lysodeikticus protoplasts]. / Sravnenie liticheskogo deistviia gramitsidina S i ego proizvodnykh na protoplasty Bacillus megaterium i Micrococcus lysodeikticus.

Essential differences were found between the lytic action of gramicidin S. on Bacillus megaterium protoplasts and that on Micrococcus lysodeikticus protoplasts. When protoplasts were suspended in a sucrose solution in phosphate buffer, the lytic activity of gramicidin S toward B. megaterium protoplasts increased with a rise in the antibiotic concentration; the lytic action of gramicidin S on M. lysodeikticus protoplasts was characterized by a complex concentration dependence. Gramicidin S derivatives lacking basic properties since the amino groups of their ornithine residues were either substituted with urea residues (carbamoyl gramicidin) of acetylated (diacetyl gramicidin) showed a high lytic activity toward the both bacterial species. In contrast to gramicidin S, the derivatives virtually did not change the permeability of cytoplasmic membranes when they acted on intact cells. In the absence of phosphates (when protoplasts were suspended in an aqueous sucrose solution), the lytic activity of gramicidin S decreased while carbamoyl gramicidin and diacetyl gramicidin still were capable of causing lysis of M. lysodeikticus protoplasts though not of B. megaterium protoplasts.

[Effect of polyene antibiotics on bacterial protoplasts]. / Deistvie polienovykh antibiotikov na bakterial'nye protoplasty.

The carbonyl-conjugated pentaenes flavofungin, nigrofungin and flavopentin exhibit considerable lytic activity toward Micrococcus lysodeikticus and Bacillus megaterium protoplasts. The antibiotics at concentrations of 5 to 14 microgram/ml cause lysis of 50% of the protoplasts within 15 min of their incubation. The antibiotics inhibit the activity of NADH oxidase and malate oxidase by 50% in the lysates of Micrococcus lysodeikticus and Bacillus megaterium protoplasts at concentrations of 30 to 50 microgram/ml; preincubation of the lysates with the antibiotics intensify the inhibiting action of the polyenes. Growth of the bacteria is inhibited when the minimal concentration of the polyenes is 75 to 100 microgram/ml. Interaction of the polyenes with bacterial membranes lacking sterols indicates that resistance of at least some bacteria to polyenes is caused by impermeability of the cell wall for these substances rather than by the absence of sterols in the membranes.

[Lysis of bacterial protoplasts and spheroplasts and suppression of their dehydrogenase activity by neotehomycin]. / Lizis neotelomitsinom bakterial'nykh protoplastov i sferoplastov i podavlenie ikh degidrogenaznoi aktivnosti.

Neotelomycin induced lysis of the protoplasts of Bac. megaterium and inhibited their succinate dehydrogenase activity. Direct correlation between the lytic activity of the antibiotic and its effect on succinate dehydrogenase was found. Neotelomycin had no effect on the dehydrogenase activity of the protoplast lysates. Possibly, suppression of the protoplast succinate dehydrogenase of Bac. megaterium under the effect of neotelomycin was due to significant structural changes caused by the antibiotic in the protoplast membranes and leading to their lysis and not to the direct effect on the enzyme. Neotelomycin had practically no effect on the spheroplast dehydrogenase activity of E. coli resistant to the antibiotic and did not induce their lysis. Resistance of E. coli to neotelomycin must be associated not with the presence of the antibiotic non-permeable cell wall but the peculiar properties of the membrane cytoplasm.

[Action of neotelomycin derivatives on bacillus magaterium cells]. / Deistvie proizvodnykh neotelomitsina na kletki bacillus magaterium

The effect of neotelomycin derivatives on the cells of Bac. megaterium was studied. Derivatives with modification of one of the two active centers of the antibiotic molecule, i.e. the free alpha-amine group of the residue of asparaginic acid or hydrophobic triptophanic structure were studied. The derivative with modified indol rings of the residues of beta-methyl-and dehydrotriptophane induced the same though lower damages as the natural antibiotic: increased permeability of the cytoplasmic membranes, protoplast lysis, suppression of the dehydrogenase activity. The activity of this derivative was due to the free amino group and amounted approximately to 3 per cent of the activity of neotelomycin. The derivative with the free amino group of the asparaginic acid residue replaced by the benzoylic group showed a high antibacterial activity but had almost no effect on the membrane permeability and a very low lytic effect. The capacity of this derivative to inhibit the bacterial dehydrogenase activity remained relatively high. Possibly the free amino group of the asparaginic acid residue provided neotelomycin with the capacity for damaging the structure of the bacterial cytoplasmic membranes. No detectable damages in the membrane state after exposure to the benzoylic derivative, as well as its high antibacterial activity are evident of the fact that the mechanism of action of the benzoylic derivative on the cells was in principal different from that of the derivative preserving the free amino group. The triptophane structure was probably not only the center actively affecting the cell but also the factor that provided the antibiotic molecule with conformation most favourable for the action of the free amino group on the membrane structures.

[Teichoic acid content in the cell wall of Actinomyces rimosus LST-118 in the process of ontogeny]. / Soderzhanie teikhoevoi kisloty v kletochnoi stenke Actinomyces rimosus LST-118 v protsesse ontogeneza

Polymeric compounds of the cell walls of Act. rimosus were studied during the actinomycete growth. It was found that the content of teichoic acid decreased 2 times by the end of development of Act. rimosus, while content of glycane polymer remained approximately at the same level. The molar ratios of teichoic acid and glycopeptide glycane were determined.