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Biomedical subjects

R B Sykes

Publications and source records attributed to R B Sykes.

At least 55 records · Page 3Linked to original sources
PubMed1982

SQ 26,180, a novel monobactam. I Taxonomy, fermentation and biological properties.

Strains of Chromobacterium violaceum, isolated from various environments, were found to produce a novel monocyclic beta-lactam antibiotic. The antibiotic, SQ 26,180 was weakly active against Gram-positive and Gram-negative bacteria with the exception of mutants hypersensitive to beta-lactam antibiotics. The compound was highly stable to beta-lactamases and acted as an inhibitor of the P99 enzyme from Enterobacter cloacae. SQ 26,180 showed affinity for penicillin-binding proteins 1a, 4 and 5/6 of Escherichia coli and inhibited R61 DD-carboxypeptidases.

Anti-Bacterial Agents↗
PubMed1982

Distribution of beta-lactam and beta-lactone producing bacteria in nature.

Over one million bacteria were isolated from a large variety of soil, plant and water samples collected from different environments and examined in an extremely sensitive and highly specific screen for beta-lactam production. A group of seven related monocyclic beta-lactams (monobactams) were isolated from strains representing four genera-Agrobacterium, Chromobacterium, Gluconobacter and Pseudomonas. Monobactam-producing strains of Agrobacterium and Pseudomonas were isolated only rarely. Producing strains of Chromobacterium were isolated from a relatively limited number of habitats while the Gluconobacter strains appeared to be widespread in nature. In addition, three closely related beta-lactone-containing molecules were isolated from strains representing three genera-Arthrobacter, Bacillus and Pseudomonas. The Bacillus and Pseudomonas strains were isolated infrequently but from a variety of samples. The producing strain of Arthrobacter was isolated only once.

Anti-Bacterial Agents↗
PubMed1981

Siderochelin, a new ferrous-ion chelating agent produced by Nocardia.

A new ferrous-ion chelating agent, siderochelin, was isolated from fermentation broths of Nocardia sp. SC 11,340. Siderochelin was produced by conventional submerged culture and purified by solvent extraction and recrystallization. The antibiotic was crystallized from acetonitrile as a mixture of diastereoisomers. The molecular formula of siderochelin was determined as C11H13N3O3 on the basis of elemental analysis and mass spectrometry, and the structure was elucidated by X-ray crystallography. The compound shows a broad spectrum of antimicrobial activity, being active against bacteria, fungi and protozoa.

Anti-Bacterial Agents↗
PubMed1980

The sensitivity of urinary isolates to cefuroxime, a new beta-lactamase stable cephalosporin.

The sensitivities to cefuroxime and cephaloridine were compared in 500 bacterial isolates from consecutive cases of urinary tract infection. In the first 200 organisms there was generally good correlation between the diameters of the zone of inhibition around a 30 microgram cefuroxime disc and the MICs. Correlation was poorest with streptococci. From the preliminary observations, criteria were derived to relate the disc sensitivities to MICs for all 500 strains. Neither cephalosporin had significant activity against Pseudomonas spp. but, apart from one strain of Klebsiella and one methicillin-resistant staphylococcus, the only bacteria sensitive to cephaloridine but resistant to cefuroxime were Str. faecalis. Of the 500 organisms, 45% were beta-lactamase-producing Gram-negative bacilli and, overall, cefuroxime was more active than cephaloridine against them. The greater stability of cefuroxime to the beta-lactamases from these bacilli were also supported by a smaller increase in MIC when the inoculum size was increased. On the basis of these results, cefuroxime should prove an effective choice for the treatment of most urinary tract infections.

Bacteria↗
PubMed1980

Izumenolide-a novel beta-lactamase inhibitor produced by Micromonospora. I. Detection, isolation and characterization.

Micromonospora chalcea subsp. izumensis produces a novel beta-lactamase inhibitor izumenolide (EM4615). Isolation of izumenolide was performed by extraction into butanol under acidic conditions and then back extraction into water at neutrality. The compound was precipitated from the aqueous phase by the addition of calcium or barium salts. Further purification was achieved by distribution in BuOH - 1 N NaOH. Izumenolide is a macrolide containing sulfate ester groups.

Chemical Phenomena↗
PubMed1980

Izumenolide-a novel beta-lactamase inhibitor produced by Micromonospora. II. Biological properties.

Izumenolide is a potent inhibitor of beta-lactamases, especially from Gram-negative bacteria. The I50 value of 0.01 microgram/ml for TEM-2 beta-lactamase, after 10 min preincubation, corresponds to a ratio of 7.6 moles inhibitor per mole of enzyme. The initial inhibitory reaction with TEM-2 beta-lactamase exhibits mixed reaction kinetics, suggesting a possible overlapping binding site with the active center. Tem-2 beta-lactamase is irreversible inactivated by izumenolide in a biphasic reaction. Carbenicillin offers partial protection against inactivation. Izumenolide exhibits limited antibiotic activity against some Gram-negative bacteria. Against beta-lactamase producing bacteria izumenolide provides protection to ampicillin and cephaloridine but the protection is limited due to permeability problems associated with izumenolide entry into the cells.

Animals↗
PubMed1978

beta-lactamases and R-plasmids of Haemophilus influenzae.

The emergence of resistance to ampicillin and other antibiotics in Haemophilus influenzae has been a relatively recent event. In contrast, drug resistance has been rampant in the Enterobacteriaceae for many years. Ampicillin-resistance in H. influenzae is almost invariably attributable to possession of the TEM (Type III a)beta-lactamase. As is common in other bacteria the gene specifying this enzyme is plasmid-borne in Haemophilus. Some ampicillin-resistant strains of H. influenzae can transfer the TEM beta-lactamase gene to other strains of Haemophilus, to Escherichia coli and to Pseudomonas aeruginosa. The features of such transfer are unusual and lead for example, to the induction of adenine requirement in recipient strains of P. aeruginosa. Crypticity measurements of beta-lactamase activity show that in comparison to P. aeruginosa or E. coli, the outer membrane of H. influenzae affords only a weak penetration barrier to beta-lactam antibiotics. This may have consequences for the stability and distribution of beta-lactamase production in Haemophilus spp. which are discussed. A comparison of the molecular properties of R-plasmids determining a variety of resistances and carried by strains of H. influenzae isolated in diverse geographical locations has revealed unexpected homologies. A series of such plasmids of similar molecular weights (about 30 X 10(6)) differ substantially only in the transposable resistance genes that they carry. A model based on these findings is presented to explain the acquisition of ampicillin- and other resistances by Haemophilus.

Amidohydrolases↗
PubMed1977

Transfer of a plasmid-specified beta-lactamase gene from Haemophilus influenzae.

A number of ampicillin-resistant strains of Haemophilus influenzae could donate a gene specifying the type IIIa (TEM) beta-lactamase to Haemophilus parainfluenzae, Escherichia coli, and Pseudomonas aeruginosa. Donor strains rapidly lost their ability to transfer ampicillin resistance on storage or subculture. Such strains also apparently contained a single species of covalently closed circular deoxyribonucleic acid of contour length 1.2 mum, equivalent to about 2.5 x 10(6) daltons. No species of plasmid deoxyribonucleic acid large enough to encode sex factor activity was detected. Despite this, transfer occurred to several bacterial genera in the presence of deoxyribonuclease, suggesting that transmissibility was by conjugation. The beta-lactamase gene was generally unstable after transfer and was lost in the absence of selection. Where stable transcipients were found, this was evidently by insertion of the beta-lactamase gene into the host chromosome. In P. aeruginosa insertion was always accompanied by induction of auxotrophy for adenine, suggesting insertion at a specific site. It is believed that insertion also occurred at one site on the chromosome of Escherichia coli. Crypticity measurements for beta-lactamase activity showed that there was little or no penetration barrier to beta-lactam drugs in Haemophilus. This may explain the long delay in the acquisition of ampicillin resistance by this organism.

Ampicillin↗
PubMed1977

Comparative acitivity of ampicillin and cefuroxime against three types of Haemophilus influenzae.

On the basis of their susceptibility to ampicillin, strains of Haemophilus influenzae can be divided into three types: type 1 are normally susceptible strains, type 2 produce stable spheroplasts from low inocula, and type 3 are beta-lactamase producers. Because of the production of spheroplasts, standard broth and agar dilution techniques have failed to differentiate between the responses of type 2 and 3 strains to ampicillin, or to identify the superiority of cefuroxime over ampicillin against the beta-lactamase-producing strains. Disk susceptibility tests with heavily seeded plates were also difficult to interpret. To overcome these problems, we developed a medium that supports the growth of H. influenzae, but not survival of spheroplasts, thereby reducing the complicating influence of spheroplast formation. Utilization of the medium made it possible to identify beta-lactamase-producing strains via both minimal inhibitory concentration and disk susceptibility techniques, as well as the superiority of cefuroxime over ampicillin against such strains. In vivo experiments showed that cefuroxime and ampicillin are equally active against infections with type 1 and 2 strains, but that cefuroxime is superior to ampicillin against infections with type 3 beta-lactamase-producing strains.

Ampicillin↗