[Streptomycetes in the Light of the Concept of Multicellularity of Bacteria.]

The review concerns discussion of certain aspects of growth and development of streptomycetes, that have an adaptation meaning for their existence under natural conditions and reflect our perception of them as procaryotes which have a range of qualities typical of multicellular organisms. At present, the concept of multicellularity is the key idea in investigation of growth processes, differentiation and physiology of streptomycetes. Streptomyces olivocinereus is presented as an effective model that gives the unique opportunities for investigation of different aspects of biology of streptomycetes within laboratory environment as well as in natural environment in suli. S.olivocinereus produces luminescent antibiotic geliomycin (resistomycin). In this review we summarized the results of the many years of investigation of growth, differentiation and behavior of this streptomycete. The investigations were undertaken by a group of scientists of the Moscow State University. The results can be employed as arguments for the multicellular nature of streptomycetes.

Secondary Metabolites from Marine Microorganisms. II. Marine Fungi and Their Habitats.

Marine-derived fungi are of great interest as a new promising source of biologically active products such as anticancer compounds, antibiotics, inhibitors of biochemical processes. Since marine organisms inhabit biologically competitive environment with unique conditions, the chemical diversity of the secondary metabolites from marine fungi is considerably high. Recent genomic studies demonstrated that fungi can carry gene clasters encoding production of previously unknown secondary metabolites. Activation of the attenuated or silent genes would be useful either for improving activities of the known compounds or for discovery of new products.

[Secondary Metabolites from Marine Microorganisms. I. Secondary Metabolites from Marine Actinomycetes].

Review represents data on new active metabolites isolated from marine actinomycetes published in 2007 to 2014. Marine actinomycetes are an unlimited source of novel secondary metabolites with various biological activities. Among them there are antibiotics, anticancer compounds, inhibitors of biochemical processes.

[On Biofilms of Streptomycetes. II. Use in Biotechnology].

Streptomycetes or mycelial microorganisms are able to form biofilms under the natural, industrial and clinical conditions. The controlled use of biofilms in various industrial processes is much more efficient vs. the cultivation of plankton suspended cells. Optimization of biotechnological processes with the use of streptomycete biofilms is advisable in production of lactic acid and detoxication of the liquor in pyrolysis of plant biomass. Streptomycete biofilms are used in water purification systems. It is recommended to use biofilms for detoxication of wastes and bioremediation of soils contaminated with hard metals. The use of biofilms of streptomycetes producing biologically active substances is of special interest. High yields of.antibiotics and actinomycin D in particular was observed with. cultivation of antibioc-producing streptomycetes as biofilms in bioreactors of unique design.

[Streptomycetes Biofilms. I. Occurrence and Formation].

Streptomycetes, soil-dwelling mycelial bacteria, can form biofilms as indigenous components of the environment. The biofilms formed by streptomycetes exist in different ecological niches, in natural, medical, industrial environments. The biofilm-forming streptomycetes affect water quality, human health, associate with deterioration of artworks and historical monuments. The review should be of interest for researchers of the biofilm mode of streptomycetes growth.

[Microbial secondary metabolites as potential reserve of pharmaceuticals].

The major characteristics of new bioactive microbial secondary metabolites are summarized in the review. A wide range of new molecular targets are implicated in discovery of new nonantibiotic compounds with some other pharmacological activities (noninfectious diseases). Microorganisms represent fascinating resources due to their production of novel products with broad spectra of bioactivities.

[Action of antibiotics as signalling molecules].

It was thought that antibiotics should be produced by soil microorganisms to inhibit the growth of competitors in natural habitats. Yet it has been shown that antibiotics at subinhibitory concentrations may have a role as signalling molecules providing cell-to-cell communication in bacteria in the environment. Antibiotics modulate gene transcription and regulate gene expression in microbial populations. Subinhibitory concentrations of antibiotics may cause a number of phenotypic and genotypic changes in microorganisms. These transcription changes are dependent on the interaction of antibiotics with macromolecular receptors such as ribosome or RNA-polymerase. Antibiotic signalling and quorum-sensing system are important regulatory mechanisms in bacteria. It was demonstrated that antibiotics interfered with quorum-sensing system.

[Microbial antibiotic resistance: resistome, its volume, diversity and development].

The known conceptions of resistome as a complex of all the antibiotic resistance genes in the genomes of all the microorganisms, pathogenic and nonpathogenic ones, in nature are considered. The data on the origin, evolution and distribution of antibiotic resistance genes and possible approaches to the resistance distribution control are presented.

[Biologically active nonribosomal peptides. III. Mechanism of biosynthesis of nonribosomal peptides].

The third part of the review is concerned with investigation of nonribosomal peptides.

[Biologically active nonribosomal peptides. I. Nonribosamal polypeptide antibiotics].

The data on novel polypeptide antibiotics described within the last 10-15 years, as well as new researches on the known antibiotics with respect to their mechanisms of action and microbial resistance are presented.

[Impact of exogenous glycine on actinomycin D resistance of Staphylococcus aureus strain adapted to the antibiotic].

The impact of glycine, added to the cultivation medium, on resistance of Staphylococcus aureus strains to actinomycin D and gramicidin S was studied. The antibiotic resistant strains were isolated after cultivation of the susceptible S. aureus strain 209P on media with increasing concentrations of actinomycin or gramicidin. When the strains were grown on the glycine-containing medium. i. e. under the conditions providing replacement of D-alanine by glycine in the C-end dipeptides of peptidoglycanes, the resistance of the staphylococci to actinomycin markedly decreased. However, in the resistant cells, characterized by significant thickening of the cell walls, the peptidoglycane quantity per a biomass unit did not lower, that was evident of preservation of the wall thickness. At the same time, with addition of glycine to the medium there was observed increased ability of the cells to bind actinomycin. When the gramicidin-adapted strains were grown on the glycine-containing medium, their resistance to the antibiotic did not change. The modification of the peptidoglycane C-end dipeptides probably lowered the protective role of the thicker walls of the cells on their contact with actinomycin but not gramicidin.

[Cell wall components in Staphylococcus aureus with double resistance to gramicidin S and actinomycin D].

Cell walls of Staphylococcus aureus R9/80 resistant to gramicidin S and actinomycin D were investigated. The strain was isolated after passages of a previously isolated strain of S. aureus with resistance to gramicidin and definite changes in the cell walls, a medium with increasing concentrations of actinomycin being used for the passages. The data on the study of the cell walls of the strain with the double resistance were compared with the results of the investigation of the cell walls of the strain susceptible to gramicidin, the gramicidin resistant strain (initial for strain R9/80) and the actinomycin adapted strain that also showed changes in the cell walls. The cell walls of the resistant strains had no significant changes in the peptidoglycane and glucosamine levels, as well as in the peptidoglycane amino acid composition. Teichoic acids of all the strains had different levels of substitution of ribite by D-alanine (a factor influencing the negative charge of teichoic acids and the wall at large). It was noted that all the strains resistant to the tested antibiotics had lower levels of teichoic acids in the cell walls. The resistant cells showed some increase of the lipid component in the walls: from 1.6% in the susceptible strain to 2.1-2.9% in the resistant cells. The main trend of the changes in the resistance development was revealed to be the thickening of the cell wall and its consolidation. The development of resistance to gramicidin, actinomycin and to both the antibiotics provoked respectively a 2.4-, 4- and 5.4-fold increase of the content of the main cell component. i.e. peptidoglycane in the cell biomass. The barrier role of the cell walls in the resistant strains and their ability to bind the antibiotic is discussed.

[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.

[Use of the method of protoplast fusion in the selection of a nisin producer]. / Ispol'zovanie metoda sliianiia protoplastov v selektsii produtsenta nizina.

Experimental data on selection of Streptococcus lactis producing the polypeptide antibiotic nisin with the method of protoplast fusing, one of the modern methods of cell engineering are presented. Four strains of Streptococcus lactis differing in their nisin-producing levels and difficult for protoplasting were used in the study. It was shown possible to transfer them to the protoplast form when respective conditions for their preliminary cultivation and regeneration are provided. Distinctive features of these strains with respect to the antibiotic resistance, sugar fermentation and growth component requirements were revealed. The protoplast fusing yielded hybrids differing from the parent strains by a number of phenotypical features and nisin-synthesizing activity.

[Kinetic aspects of the relation of the growth of the producer and the biosynthesis of heliomycin depending on the carbon source in the medium]. / Kineticheskie aspekty sootnosheniia rosta produtsenta i biosinteza geliomitsina v zavisimosti ot istochnika ugleroda v srede.

Kinetic parameters of Streptomyces olivocinereus 11-98 growth and biosynthesis of heliomycin were studied. It was shown that carbon sources such as glycerol, mannitol and ramnose were the most favourable for the antibiotic biosynthesis. These carbon sources belonged to the group of substances providing high growth rates of the culture. Ranging of the culture growth rates and antibiotic production levels revealed a set of carbon sources providing a converse relationship between the growth rate and antibiotic biosynthesis i.e. L-arabinose, potassium gluconate, raffinose and sucrose. It was suggested that these compounds were catabolic type regulators of heliomycin biosynthesis.

[Cell wall components of gramicidin S resistant Staphylococcus aureus]. / Izuchenie komponentov kletochnoi stenki Staphylococcus aureus, ustoichivogo k gramitsidinu S.

Comparative study of two staphylococcus aureus 209P strains--resistant and susceptible to gramicidin S demonstrated that peptidoglycanes of two strains differ by ratio glycine/serine at peptide bridges. Besides peptidoglycanes significantly differ by amidation of alfa-carboxyles of glutamic acid in muropeptide. This peptidoglycane modification of resistant cells along with enhanced content of etherized D-alanine in teichoic acid provides lower negative charge of cell wall components. It may influence the cell wall ability to react with positively charged gramicidin molecules. It was shown that isolated cell walls and peptidoglycane of resistant cells binds significantly less gramicidin than cell walls and peptodoglyce of susceptable cells. Simultaneous determination of gramicidin binding by intact S. aureus cells and their killing revealed that lower ability of resistant cells to bind gramicidin is significant but not critical factor of gramicidin resistance.

[Comparative study on the activity of some enzyme systems in cells of gramicidin S sensitive and resistant strains of Staphylococcus aureus]. / Sravnitel'noe izuchenie aktivnosti nekotorykh fermentnykh sistem v kletkakh chuvstvitel'nogo i ustoichivogo k gramitsidinu S shtammov Staphylococcus aureus.

Polarographic determination of the rate of endogenic respiration of the cells of Staphylococcus aureus 209P showed that the respiration activity of the cells of the strain resistant to 20 micrograms/ml of gramicidin S was 20 to 30 per cent lower than that of the sensitive strain. The rate of oxygen consumption in oxidation of NADH by the membrane preparations of the resistant cells was also 25 to 30 per cent lower. By comparison with the initial sensitive strain the activity of endogenic DPI-reductases of the intact cells and NADH-dehydrogenases of the membranes of the resistant strain was also lower. The velocity of the valine transport to the resistant cells was much lower than that of the amino acid transport to the cells of the sensitive strain. Development of gramicidin S resistance in the staphylococcal strain was likely accompanied by a decrease in the activity of the energy metabolism in the membranes.