PubMed Health⌕ Search

Biomedical subjects

E Cundliffe

Publications and source records attributed to E Cundliffe.

At least 73 records · Page 4Linked to original sources
PubMed1983

Site of action of a ribosomal RNA methylase responsible for resistance to erythromycin and other antibiotics.

The enzyme which confers resistance to erythromycin in the producing organism Streptomyces erythraeus dimethylates a single adenine residue in Bacillus stearothermophilus 23 S rRNA. This corresponds to residue Ade 2058 in Escherichia coli 23 S RNA. The methylase responsible for resistance to macrolides, lincomycin, and streptogramin B-related antibiotics in Staphylococcus aureus also acts at this site.

Anti-Bacterial Agents↗
PubMed1982

Structural modifications of anguidin and antitumor activities of its analogues.

Approximately 60 derivatives of anguidin were prepared for evaluation of antitumor activities. Positions 3, 4, 8-10, and 15 were modified, and the resultant derivatives were screened against P-388 leukemia. It was found that introduction of the C3-keto and C3,C8-diketo groups markedly improved the antileukemic activity, whereas epoxidation of the C9-C10 double bond or oxidation of the C15 position diminished its activity. Selected derivatives were further tested in the L1210, B16, Lewis lung, Colon 36, and Colon 38 tumor lines. Among these compounds, 4 beta, 15-diacetoxyscirpene-3,8-dione (54) and 4 beta-(chloroacetoxy)-15-acetoxyscirpene-3,8-dione (55) were found to be most active in various tumors. Inhibitory action of several analogues on protein synthesis was also examined using H-HeLa cells.

Animals↗
PubMed1982

The mode of action of berninamycin and mechanism of resistance in the producing organism, Streptomyces bernensis.

The mode of action of berninamycin on bacterial protein synthesis is related to that of thiostrepton, a dissimilar compound. Both antibiotics bind to the complex of 23S RNA with protein L11 and both affect various functions of the ribosomal A site. Also, Streptomyces bernensis and Streptomyces azureus (which, respectively, produce berninamycin and thiostrepton) possess similar ribosomal RNA methylases capable of rendering ribosomes resistant to these compounds. Resistance involves specific pentose-methylation of 23S ribosomal RNA.

Anti-Bacterial Agents↗
PubMed1982

Biochemical characterization of resistance determinants cloned from antibiotic-producing streptomycetes.

Determinants of antibiotic resistance have been cloned from four antibiotic-producing streptomycetes into Streptomyces lividans. Biochemical analyses of resistant clones revealed the presence of enzymes that had previously been characterized as likely resistance determinants in the producing organisms. These included: 23S rRNA methylases from S. azureus and S. erythreus, which confer resistance to thiostrepton and erythromycin, respectively; viomycin phosphotransferase from S. vinaceus; and aminoglycoside phosphotransferase and acetyltransferase from the neomycin producer S. fradiae. In general, the levels of antibiotic resistance of the clones were similar to those of the producing organisms. Although the two aminoglycoside-modifying enzymes from S. fradiae could independently confer only low-level resistance to neomycin, the presence of both enzymes in the same strain resulted in a level of resistance comparable with that of the producing organism.

Acetyltransferases↗
PubMed1981

The binding site for ribosomal protein L11 within 23 S ribosomal RNA of Escherichia coli.

Ribosomal protein L11 of Escherichia coli was bound to 23 S rRNA and the resultant complex was digested with ribonuclease T1. A single RNA fragment, protected by protein L11, was isolated from such digests and was shown to rebind specifically to protein L11. The nucleotide sequence of this RNA fragment was examined by two-dimensional fingerprinting of ribonuclease digests. It proved to be 61 residues long and the constituent oligonucleotides could be fitted perfectly between residues 1052 and 1112 of the nucleotide sequence of E. coli 23 S rRNA.

Bacterial Proteins↗
PubMed1981

Chloramphenicol resistance that does not involve chloramphenicol acetyltransferase encoded by plasmids from gram-negative bacteria.

Chloramphenicol resistance-specifying plasmids from incompatibility groups P-1 and C did not encode chloramphenicol acetyltransferase (CAT). Expression of resistance was inducible by subinhibitory concentrations of the drug. The mechanism of resistance was thought to be a cytoplasmic membrane-located barrier to the permeability of the drug into the cell. No evidence for the inactivation of the drug was obtained. In vitro polypeptide synthesis directed by ribosomes isolated from resistant and sensitive cells was equally sensitive to inhibition by chloramphenicol suggesting that a ribosomal mechanism was not involved. Spheroplasts expressed the same level of resistance as whole cells. Strains specifying intracellular CAT did not degrade chloramphenicol in the culture medium if they also carried a chloramphenicol resistance plasmid not specifying CAT.

Acetyltransferases↗
PubMed1981

The mode of action of nosiheptide (multhiomycin) and the mechanism of resistance in the producing organism.

The mode of action of nosiheptide (multhiomycin) on bacterial protein synthesis is closely similar to that of thiostrepton. Both antibiotics inhibit functions of elongation factors Tu and G and greatly reduce the synthesis of guanosine penta- and tetraphosphates in response to stringent factor. Furthermore, the actinomycetes which produce these antibiotics defend themselves against their products in similar fashion. This involves specific pentose-methylation of 23S ribosomal RNA.

Anti-Bacterial Agents↗
PubMed1981

Concerning the mode of action of micrococcin upon bacterial protein synthesis.

The antibiotic, micrococcin, binds to complexes formed between bacterial 23-S ribosomal RNA and ribosomal protein L11 and, in doing so, inhibits of thiostrepton. In assay systems simulating partial reaction of protein synthesis, micrococcin inhibits a number of processes believed to involve the ribosomal A site while stimulating GTP hydrolysis dependent upon ribosomes and elongation factor EF-G. The latter effect is not observed upon ribosomes lacking a protein homologous with protein L11. Nor is it apparent upon those containing 23-S RNA previously subjected to the action of a specific methylase known to render ribosomes resistant to thiostrepton. It is concluded that stimulation by micrococcin of factor-dependent GTP hydrolysis results from the binding of the drug to its normal target site which involves 23-S RNA and protein L11.

Anti-Bacterial Agents↗
PubMed1980

Mutants of Escherichia coli lacking ribosomal protein L11.

Three mutants with ribosomes apparently lacking Protein L11, AM68, AM76, and AM77, were investigated using a variety of immunological techniques to determine whether L11 was indeed lacking. Ouchterlony double diffusion, modified immunoelectrophoresis, and dimer formation on sucrose gradients all gave results indicating Protein L11 was missing from the ribosome in these mutants. Electron micrographs of ribosomes of the mutants were indistinguishable from those of wild type. Ribosomes of AM68, AM76, and AM77, did not bind the antibiotic thiostrepton, but binding was recovered upon reconstitution with wild type Protein L11.

Antigen-Antibody Complex↗
PubMed1980

Ribosomal resistance to the 12,13-epoxytrichothecene antibiotics in the producing organism Myrothecium verrucaria.

An extract of Myrothecium verrucaria, a fungus which produces a range of 12,13-epoxytrichothecene toxins, was found to be resistant to T-2 toxin, one of its products. The epoxytrichothecenes are inhibitors of eukaryotic protein synthesis and normally bind to the 60S ribosomal subunit so as to inhibit peptidyltransferase activity. Ribosomes from M. verrucaria contain 60S subunits which are not subject to inhibition by T-2 toxin and are also resistant to certain other drugs such as anisomycin and homoharringtonine, but not sparsomycin or cycloheximide.

Anti-Bacterial Agents↗
PubMed1980

Functional homology between E. coli ribosomal protein L11 and B. megaterium protein BM-L11.

Ribosomes from the thiostrepton-resistant mutant MJ1 of Bacillus megaterium completely lack a protein designated BM-L11. When assayed in vitro, such ribosomes show an impaired ability to hydrolyse GTP in the presence of the elongation factor EF-G and are unable to support the synthesis of (p)ppGpp in response to the stringent factor. Restoration of both these activities can be achieved by re-addition of either protein BM-L11 or its serological homologue from Escherichia coli, protein L11, implying that these two proteins are related functionally as well as immunologically.

Bacillus megaterium↗
PubMed1980

Resistance to the antibiotics viomycin and capreomycin in the Streptomyces species which produce them.

Viomycin capreomycin, antibiotics produced by Streptomyces vinaceus and S. capreolus respectively, are potent inhibitors of bacterial protein synthesis. Although these organisms are highly tolerant of their own products in vivo, their ribosomes are fully sensitive to the action of the drugs in vitro. However, they processes novel, antibiotic-inactivating enzymes (viomycin phosphotransferase, capreomycin phosphotransferase, capreomycin acetyltransferase) which, in addition to possible biosynthetic roles, may contribute to the resistances observed in vivo.

Alkaline Phosphatase↗
PubMed1980

Resistance to thiostrepton, siomycin, and sporangiomycin in actinomycetes that produce them.

The antibiotics thiostrepton, siomycin, and sporangiomycin are closely related both in structure and in mode of action. Actinomycetes which produce this group of compounds possess ribonucleic acid-pentose methylases, which act upon 23S ribosomal ribonucleic acid and render ribosomes resistant to the action of these antibiotics. This is achieved via the formation of a single residue of 2'-O-methyladenosine per ribosome.

Actinomycetales↗