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At least 433 records · Page 24Linked to original sources
PubMed1978

Semisynthetic aminoglycoside antibacterials. 6. Synthesis of sisomicin, Antibiotic G-52, and novel 6'-substituted analogues of sisomicin from aminoglycoside 66-40C.

The discovery of aminoglycoside 66-40C, a novel dimeric, unsaturated imine produced by Micromonospora inyoensis, afforded a versatile intermediate for the synthesis of a variety of sisomicin analogues modified at the 6' position. The conversion of 66-40C into sisomicin, antibiotic G-52, and a series of novel 6'-substituted analogues of sisomicin is described, and the biological activity of the products is discussed.

Aminoglycosides↗
PubMed2000

Chromosome topology and genome size of selected actinomycetes species.

Information about the genome organization of actinomycetes species is restricted to a few genera: Corynebacterium, Mycobacterium, Rhodococcus, Saccharopolyspora and Streptomyces. Streptomyces species and Saccharopolyspora erythraea were shown to contain a single linear 8 Mb chromosome. In contrast, the Corynebacterium, Mycobacterium and Rhodococcus species studied were demonstrated to possess a smaller (3 Mb-6.5 Mb) single circular chromosome. To investigate whether linear chromosome topology and genome sizes above 7 Mb are unique features of Streptomyces and S. erythraea we have started to investigate the chromosome topology, the genome size and the status of accessory elements of additional actinomycetes species: Actinoplanes philippinensis, Amycolatopsis orientalis, Micromonospora chalcea, Nocardia asteroides, Rhodococcus opacus and Streptoverticillium abikoense. Our data which are based on PFGE experiments clearly suggest that large genome sizes and chromosome linearity are seen in mycelium forming actinomycetes genera. In addition we have identified large linear plasmids in Nocardia asteroides, Streptoverticillium abikoense and Rhodococcus opacus.

Actinomycetales↗
PubMed1999

Mode of action of thiocoraline, a natural marine compound with anti-tumour activity.

Thiocoraline, a new anticancer agent derived from the marine actinomycete Micromonospora marina, was found to induce profound perturbations of the cell cycle. On both LoVo and SW620 human colon cancer cell lines, thiocoraline caused an arrest in G1 phase of the cell cycle and a decrease in the rate of S phase progression towards G2/M phases, as assessed by using bromodeoxyuridine/DNA biparametric flow cytometric analysis. Thiocoraline does not inhibit DNA-topoisomerase II enzymes in vitro, nor does it induce DNA breakage in cells exposed to effective drug concentrations. The cell cycle effects observed after exposure to thiocoraline appear related to the inhibition of DNA replication. By using a primer extension assay it was found that thiocoraline inhibited DNA elongation by DNA polymerase alpha at concentrations that inhibited cell cycle progression and clonogenicity. These studies indicate that the new anticancer drug thiocoraline probably acts by inhibiting DNA polymerase alpha activity.

Anti-Bacterial Agents↗
PubMed2000

Biosynthesis of the anti-parasitic agent megalomicin: transformation of erythromycin to megalomicin in Saccharopolyspora erythraea.

Megalomicin is a therapeutically diverse compound which possesses antiparasitic, antiviral and antibacterial properties. It is produced by Micromonospora megalomicea and differs from the well-known macrolide antibiotic erythromycin by the addition of a unique deoxyamino sugar, megosamine, to the C-6 hydroxyl. We have cloned and sequenced a 48 kb segment of the megalomicin (meg) biosynthetic gene cluster which contains the modular polyketide synthase (PKS) and the complete pathway for megosamine biosynthesis. The similarities and distinctions between the related megalomicin and erythromycin gene clusters are discussed. Heterologous expression of the megalomicin PKS in Streptomyces lividans led to production of 6-deoxyerythronolide B, the same macrolactone intermediate for erythromycin. A 12 kb fragment harbouring the putative megosamine pathway was expressed in Saccharopolyspora erythraea, resulting in the conversion of erythromycin to megalomicin. Considering the extensive knowledge surrounding the genetic engineering of the erythromycin PKS and the familiarity with genetic manipulation and fermentation of S. erythraea, the ability to produce megalomicin in this strain should allow the engineering of novel megalomicin analogues with potentially improved therapeutic activities.

Anti-Bacterial Agents↗
PubMed1999

Macrolide antibiotics, drug interactions and microsomal enzymes: implications for veterinary medicine.

The macrolide group of antibiotics includes natural members, pro-drugs and semi-synthetic derivatives, thus named because they are composed of a large aglycone ring (from 14 to 16 carbon atoms), to which are attached several sugars. Some of them are amino-sugars, containing a diethylamino, tertiary amine function. A number of antibiotics, including erythromycin, oleandomycin, triacetyl-oleandomycin (troleandomycin), carbomycin, spiramycin, tylosin, rosamicin, azithromycin, clarithromycin, dirithromycin and others, are members of this group. On a comparative basis, erythromycin and oleandomycin are similar, with the same basic 14-carbon lactone ring and side chain sugars. The remaining compounds contain a basic 15- or 16-carbon lactone ring and one or two side-chain sugars. Most of the macrolides are produced by Streptomyces spp bacteria. An exception is rosamicin, which is produced by Micromonospora. Clarithromycin and azithromycin are new semi-synthetic derivatives of erythromycin.

Animals↗
PubMed2007

Structure and role of sialic acids on the surface of Aspergillus fumigatus conidiospores.

Aspergillus fumigatus is an opportunistic fungal pathogen that causes a life-threatening invasive fungal disease (invasive aspergillosis, IA) in immunocompromised individuals. The first step of pathogenesis is thought to be the attachment of conidia to proteins in lung tissue. Previous studies in our laboratory have shown that conidia adhere to basal lamina proteins via negatively charged sugars on their surface, presumably sialic acids. Sialic acids are a family of more than 50 substituted derivatives of a nine-carbon monosaccharide, neuraminic acid. The purpose of this study was 2-fold: (1) to determine the structure of sialic acids and the glycan acceptor on A. fumigatus oligosaccharides and (2) to determine the effect on the removal of sialic acids from conidia on conidial binding to the extracellular matrix protein fibronectin and phagocytosis of conidia by cultured macrophages and type 2 pneumocytes. Surface sialic acids were removed using Micromonospora viridifaciens sialidase or using acetic acid, mild acid hydrolysis. Lectin binding studies revealed that the majority of conidial sialic acids are alpha2,6-linked to a galactose residue. High-pressure liquid chromatography of derivatized sialic acids released from conidia revealed that unsubstituted N-acetylneuraminic acid is the predominant sialic acid on the surface of conidia. Enzymatic removal of sialic acid significantly decreased the binding of conidia to fibronectin by greater than 65% when compared with sham-treated controls. In addition, removal of sialic acids decreased conidial uptake by cultured murine macrophages and Type 2 pneumocytes by 33% and 53%, respectively. Hence, sialylated molecules on A. fumigatus conidia are ligands for both professional and nonprofessional phagocytes.

Aspergillus fumigatus↗
PubMed2002

Stressful death of T-ALL tumor cells after treatment with the anti-tumor agent Tetrocarcin-A.

The T-ALL cell lines CCRF-CEM and Jurkat were studied for their sensitivity toward apoptosis induced by tetrocarcin-A (TC-A), an antibacterial and antitumor agent isolated from the actinomycete Micromonospora. This substance promoted cell death via a mitochondrial signaling pathway, that is, by activation of Bid and Bax, loss of the mitochondrial transmembrane potential, release of cytochrome c, and activation of effector caspases, even under conditions of Bcl-2 overexpression. Furthermore, sensitivity to TC-A was not dependent on expression of wild-type caspase-8. In contrast, this apoptotic pathway was inhibited markedly by pretreatment of cells with cycloheximide, an inhibitor of de novo protein synthesis. cDNA microarray chip analysis revealed that TC-A induced a significant up-regulation of members of the heat shock protein family known to be involved in the endoplasmic reticulum (ER)-stress-induced apoptotic program. The activation of caspase-12, the central inducer caspase involved in ER-stress by TC-A treatment, is in concordance with this result. These results show that, in T-ALL cells, TC-A induces an apoptotic machinery via mitochondrial and ER signaling, which is not inhibited by aberrant expression/function of important regulators of death receptor- and drug-induced apoptosis.

Aminoglycosides↗
PubMed1994

Chemical and molecular classification of Saccharomonospora strains.

The results of our experiments showed that the 5'-terminal sequences of 23S rRNAs can be used to distinguish different genera of actinomycetes, including the genera Streptomyces, Micromonospora, Amycolatopsis, and Saccharomonospora. There are small differences (< 1%) among the sequences of some strains belonging to the genera Streptomyces (two strains) and Saccharomonospora (seven strains). On the basis of the results of morphological and biochemical analyses, strain 9022 belongs in the genus Saccharomonospora; however, there are distinct differences in the cell wall compositions and the 5' termini of the 23S rRNA sequences of this strain and members of the genus Saccharomonospora. Hence, strain 9022 cannot be classified in the genus Saccharomonospora.

Actinomycetales↗
PubMed1995

Phylogenetic analysis of mycolic acid-containing wall-chemotype IV actinomycetes and allied taxa by partial sequencing of ribosomal protein AT-L30.

The phylogenetic relationships among 30 mycolic acid-containing wall chemotype IV actinomycete strains and 12 strains belonging to allied taxa were examined by determining the amino acid sequences of the ribosomal AT-L30 proteins of these organisms. Sequencing 20 N-terminal amino acids of AT-L30 preparations revealed that the members of the genera containing mycolic acid-containing actinomycetes form two clusters; the first cluster contains the genera Nocardia, Rhodococcus, Gordona, and Tsukamurella, and the second cluster contains the genera Corynebacterium and Mycobacterium. The genus Nocardia was placed in a clade containing the genus Rhodococcus. The data showed that Tsukamurella paurometabolum is closely related phylogenetically to the genus Gordona. The phylogenetic clusters identified were entirely consistent with the proposal of Goodfellow that the family Nocardiaceae should encompass the mycolate-containing, cell wall type IV actinomycete genera Nocardia, Rhodococcus, Gordona, and Tsukamurella. The genera Actinomyces and Micrococcus exhibited AT-L30 amino acid sequence characteristics intermediate between those of actinomycetes and those of typical eubacteria. The genera Nocardia, Gordona, Mycobacterium, Actinoplanes, and Micromonospora were each a taxon that consisted of phylogenetically coherent species. In contrast, the genera Rhodococcus and Corynebacterium are taxa that consist of phylogenetically distantly related species. In general, my results are consistent with previous 16S rRNA sequencing results, but significant differences were also found. My data, together with previous AT-L30 sequencing data, show that phylogenetic relationships among taxa can be determined by using markers other than the ribosomal gene sequences.

Actinomycetales↗
PubMed1982

Numerical classification of sporoactinomycetes containing meso-diaminopimelic acid in the cell wall.

One hundred and thirty actinomycetes representing 19 genera and 50 species were compared in a numerical phenetic survey using 108 unit characters. Data were examined using the simple matching (SSM), Jaccard (SJ) and pattern (DP) coefficients and clustering was achieved using both the single and unweighted pair group average algorithms. Cluster composition was barely affected by the statistics used or by test error, estimated at 2.1%. Over 80% of the strains were assigned to 2 clusters containing between two and 25 organisms. Most of the clusters were distinct and homogeneous though two were divided into subclusters. Some of the clusters and subclusters were equated with the established taxa Actinomadura madurae, Actinomadura pelletieri, Dermatophilus congolensis, Geodermatophilus obscurus, Microbispora spp., Micromonospora spp., Micropolyspora brevicatena, Micropolyspora faeni, Nocardia spp., Nocardiopsis (Actinomadura) dassonvillei, Planobispora spp., Planomonospora spp., Saccharomonospora viridis, Streptomyces somaliensis, Thermoactinomyces candidus, Thermoactinomyces dichotomica, Thermoactinomyces sacchari, Thermoactinomyces vulgaris and "Thermomonospora fusca'. The numerical data, together with results from previous chemical and genetical studies, provide sufficient evidence for the transfer of Micropolyspora brevicatena to Nocardia as Nocardia brevicatena comb. nov.

Actinomycetales↗
PubMed1988

Characterization of bacteriophage phi C69 of Saccharopolyspora erythraea and demonstration of heterologous actinophage propagation by transfection of Streptomyces and Saccharopolyspora.

A bacteriophage, designated phi C69, isolated from a culture of Saccharopolyspora erythraea was characterized. The phage propagates on Sac. erythraea NRRL 2338 but does not infect 10 Streptomyces or 3 Micromonospora species tested. It infects Sac. erythraea NRRL 2359 but does not produce infectious phage particles in this host. phi C69 is approximately 40 kb in length and contains cohesive ends. A cos fragment containing ligated phage DNA ends was cloned in Escherichia coli. Restriction maps of the phage DNA and the cos fragment for several enzymes are shown. Transfection of both Sac. erythraea and Streptomyces lividans with phi C69 resulted in approximately equal titres of infectious phage particles produced from approximately the same number of regenerating cells. Transfection of Sac. erythraea with DNA from Streptomyces phages SH10 and KC404 also resulted in the production of infectious phage particles. The basis for differences among hosts in susceptibility to infection by various actinophages is discussed.

Bacteriophages↗
PubMed2004

Phylogenetic analysis of the genera Streptomyces and Kitasatospora based on partial RNA polymerase beta-subunit gene (rpoB) sequences.

The RNA polymerase beta-subunit genes (rpoB) of 67 Streptomyces strains, representing 57 species, five Kitasatospora strains and Micromonospora echinospora KCTC 9549 were partially sequenced using a pair of rpoB PCR primers. Among the streptomycetes, 99.7-100 % similarity within the same species and 90.2-99.3 % similarity at the interspecific level were observed by analysis of the determined rpoB sequences. The topology of the phylogenetic tree based on rpoB sequences was similar to that of 16S rDNA. The five Kitasatospora strains formed a stable monophyletic clade and a sister group to the clade comprising all Streptomyces species. Although there were several discrepancies in the details, considerable agreement was found between the results of rpoB analysis and those of numerical phenetic classification. This study demonstrates that analysis of rpoB can be used as an alternative genetic method in parallel to conventional taxonomic methods, including numerical phenetic and 16S rDNA analyses, for the phylogenetic analyses of the genera Streptomyces and Kitasatospora.

DNA Primers↗
PubMed1998

Transfer of plasmid pTO1 from Escherichia coli to various representatives of the order Actinomycetales by intergeneric conjugation.

Plasmid pTO1 containing the oriT fragment from RK2, the Escherichia coli replication function from pBR322, and a DNA fragment of actinophage phi C31 with the attachment site was transferred from E. coli S17-1 to strains of the genera Actinomadura, Arthrobacter, Micromonospora, Nocardia, Rhodococcus, and to 16 strains of the genus Streptomyces. The frequency of conjugant formation was 1 x 10(-3)-1 x 10(-5) depending on the strain. Hybridization experiments demonstrated that plasmid pTO1 integrates into chromosomes of a number of the recipient strains examined.

Actinomycetales↗
PubMed1979

Antibacterial activities, nephrotoxicity, and ototoxicity of a new aminoglycoside, Win 42122-2.

Win 42122-2 is a new aminoglycoside antibiotic obtained from a mutant strain of Micromonospora purpurea. In vitro and in vivo comparisons of Win 42122-2 with gentamicin and amikacin revealed that Win 42122-2 generally was less active than gentamicin against Pseudomonas and many Enterobacteriacae, especially Klebsiella and indole-negative Proteus. Against most gentamicin-susceptible isolates, Win 42122-2 was more active than amikacin. Gentamicin-resistant clinical isolates were usually resistant to Win 42122-2, although it was active against certain gentamicin-resistant organisms, depending upon the aminoglycoside-modifying enzymes harbored by the organism. However, Win 42122-2 was markedly less toxic than gentamicin in subacute nephrotoxicity studies in rats, ototoxicity experiments in guinea pigs, and ataxia determinations in cats. This series of antibacterial determinations and toxicity evaluations indicated that the reduced toxicity of the antibiotic may be sufficient to provide an improved therapeutic ratio over gentamicin and other aminoglycosides, even though Win 42122-2 is less potent than gentamicin against some bacteria.

Amikacin↗
PubMed1973

Sisomicin: evaluation in vitro and comparison with gentamicin and tobramycin.

Sisomicin is a new antibiotic produced by Micromonospora inyoensis. The in vitro activities of sisomicin, gentamicin, and tobramycin, three similar aminoglycosides, were determined against 228 clinical isolates representing 10 genera of common pathogens. No difference was noted in the activities of these antimicrobial agents when assayed by a standard broth dilution technique against Klebsiella, Enterobacter, Escherichia, Salmonella, Citrobacter, enterococci, or Staphylococcus aureus. Sisomicin was significantly more active than tobramycin against Serratia and indole-positive Proteus strains. Sisomicin was significantly more active than gentamicin against indole-negative Proteus strains and slightly more active against indole-positive Proteus strains. Tobramycin was more active than sisomicin or gentamicin against Pseudomonas and indole-negative Proteus strains. Gram-negative bacilli resistant to one of the three antimicrobial agents were not necessarily resistant to either of the other two. Activity of sisomicin was independent of the susceptibility or resistance of these isolates to nine other antimicrobial agents as assayed by the Bauer-Kirby technique. The presence of 50% human serum did not antagonize the in vitro activity of sisomicin against gram-negative isolates. Because sisomicin showed certain advantages over gentamicin or tobramycin in vitro, further investigation of this new antimicrobial agent is warranted.

Aminoglycosides↗
PubMed1974

Rosamicin: evaluation in vitro and comparison with erythromycin and lincomycin.

Rosamicin is a new macrolide antibiotic produced by Micromonospora rosaria. It shares certain chemical and biological characteristics with erythromycin. Activity against gram-positive strains was assayed by broth dilution and compared to that of erythromycin and lincomycin. Rosamicin was bacteriostatic and inhibited most strains of Staphylococcus aureus, Staphylococcus epidermidis, enterococci, viridans streptococci, and group A streptococci in concentrations of 0.02 to 4.0 mug/ml. Results were similar for erythromycin and for lincomycin (excluding enterococci). Cross-resistance of gram-positive organisms to these three antimicrobial agents was incomplete. Rosamicin was more active than erythromycin against Enterobacteriaceae and Pseudomonas at pH 7.2. Alkalinization of the medium enhanced the activity of both rosamicin and erythromycin; however, rosamicin was still more active than erythromycin against all gram-negative strains at pH 7.6 and 8.0. In view of the high degree of in vitro activity of rosamicin against gram-positive organisms, lack of complete cross-resistance with erythromycin and lincomycin, and the greater activity of rosamicin than erythromycin against gram-negative organisms, further investigation of this macrolide is warranted.

Anti-Bacterial Agents↗
PubMed1974

Microbiological characterization of everninomicins B and D.

Everninomicins B and D are components of a complex of antibiotic substances produced by Micromonospora. Both were shown to be highly active inhibitors of growth of all gram-positive bacteria, Neisseria, and Bacteroides studied in vitro. Potency of activity appeared to be greater than that of chloramphenicol, but less than that of penicillin G, when assayed against strains susceptible to each of the drugs. The everninomicins were bacteriostatic for all strains tested, except group A streptococci. No facultatively anaerobic gram-negative bacilli were susceptible. Resistant mutants were selected with difficulty from susceptible staphylococci in the laboratory, and these demonstrated no cross-resistance to available antimicrobial agents. Most variations in media, growth conditions, or procedure of assay had little or no effect on antimicrobial activity. Only addition of serum or increase in inoculum size reduced antibacterial activity. Significant differences in activity of the two components were encountered infrequently; the B component was four- to sixfold more active against gonococci and group A streptococci, whereas the D component was fourfold more active against enterococci. Because of the high degree of in vitro activity and lack of resistance among susceptible genera of bacteria, the everninomicins clearly merit further careful study as potential therapeutic agents.

Aminoglycosides↗
PubMed1977

Epoxidation of aldrin to exo-dieldrin by soil bacteria.

Twenty-two strains of soil bacteria, including representatives of the genera Bacillus, Micromonospora, Mycobacterium, Nocardia, Streptomyces, Thermoactinomyces, and Pseudomonas and 10 unidentified gram-negative, motile, rod-shaped bacteria, were shown to degrade aldrin to its epoxide dieldrin. In every case, the exo-stereoisomer of dieldrin was produced exclusively.

Aldrin↗