Search PubMed⌕ Search

Biomedical subjects

S Normark

Publications and source records attributed to S Normark.

At least 163 records · Page 9Linked to original sources

Cefuroxime treatment of urethritis caused by a beta-lactamase-producing strain of Neisseria gonorrhoeae.

A patient who contracted urethritis from a beta-lactamase-producing strain of Neisseria gonorrhoeae was successfully treated with the cephalosporin derivative cefuroxime. As expected, neither cefuroxime nor cefamandole was hydrolysed by plasmid-coded gonococcal beta-lactamase. Cefuroxime ought to be a valuable and efficacious substitute for penicillins in the treatment of gonhorrhoea due to beta-lactamase-producing gonococcal strains.

Adult↗

Surface charge and hydrophobicity of Salmonella, E. coli, Gonococci in relation to their tendency to associate with animal cells.

The surface charge and hydrophobicity of Salmonella typhimurium, Escherichia coli and Neisseria gonorrhoeae bacteria have been compared with their tendency to associate in vitro with human polymorphonuclear leucocytes (PMNL) and HeLa cells in culture. It was found that lipopolysaccharide mutations in S. typhimurium or E. coli, yielding core-defective mutants, increased the surface hydrophobicity, as assessed by aqueous two-phase partitioning and hydrophobic interaction chromatography, and promoted the association with PMNL and HeLa cells. The association to HeLa cells was much smaller for the E. coli than for the S. typhimurium bacteria. All the colonial variants of N. gonorrhoeae interacted significantly with the PMNL and the HeLa cells. They were liable to hydrophobic interaction. However, the non-piliated, T3 and T4, were slightly more hydrophobic, but less negatively charged, than the piliated T1 and T2 bacteria. There was a positive correlation between possession of COA- and pili-proteins in the outer membrane and enhanced interaction with PMNL. The reverse was found with respect to association with HeLa cells. The results support the hypothesis that expression of hydrophobicity and negative charge can increase the interaction of bacteria with certain animal cells, e.g. PMNL and HeLa cells.

Escherichia coli↗

Susceptibility to penicillins and cephalosporins in beta-lactamase producing strains of E. coli and relative amount of beta-lactamase produced from these strains.

The genetic and physiological mechanisms for affecting the amount of chromosomally mediated beta-lactamase of Escherichia coli K 12 was reviewed. The presence of clinical E. coli isolates with elevated beta-lactamase production was assessed. Among cephalothin resistant isolates from patients with urinary tract infections, six E. coli strains were found to produce elevated amounts of a beta-lactamase indistinguishable from that coded by the ampC gene of E. coli K 12. The resistance levels displayed by these isolates towards a number of beta-lactams was very high as compared to E. coli strains being wild type for chromosomal beta-lactamase production. Cefuroxime and to lesser extent cefamandole were stable to hydrolysis by E. coli chromosomal beta-lactamase but acted as inhibitors of the enzyme. Nevertheless increased beta-lactamase production mediated an increased resistance towards these drugs.

Cephalosporins↗

Isolation and characterization of DNA repetitions carrying the chromosomal beta-lactamase gene of Escherichia coli K-12.

A ColEl hybrid plasmid, pNUl, carrying the amp operon coding for chromosomal beta-lactamase was isolated from the Clarke and Carbon collection and physically mapped. The physical location of ampC within this plasmid was further deduced by in vitro cloning. By reciprocal recombination between pNUl and chromosome of two unstable beta-lactamase hyperproducing E. coli K-12 mutants a large plasmid from each mutant was obtained. The respective plasmid was physically mapped and found to contain five and two repeated DNA segments. The repetitions within each plasmid were equal in size, 9,800 bp and 11,900 bp respectively and were organized in tandem. The end points of the repeats were different in the two plasmids but shared a DNA segment carrying the ampC gene. The chromosomal DNA of the beta-lactamase hyperproducing E. coli mutants were found to contain an amplified DNA segment equal in size to the repeated unit found in the respective plasmid. The data shows that up to 10 identical repeats organized in tandem can be generated by a normal mutation frequency in E. coli.

Cloning, Molecular↗

Effects of low ampicillin concentrations on penicillin sensitive and beta-lactamase producing strains of Neisseria gonorrhoeae.

The effects of therapeutic concentrations of ampicillin on non-beta-lactamase and beta-lactamase producing strains of Neisseria gonorrhoeae were studied. A small but significant fraction of bacteria in a gonococcal population was found to respond in a bacteriostatic rather than a bactericidal way upon ampicillin treatment. In agreement with this was the finding of morphologically unaltered cells in the scanning electron microscope after ampicillin exposure. Ampicillin treatment of beta-lactamase producing gonococci caused a significant release of the enzyme into the surrounding growth media. However, initially all beta-lactamase activity was cellbound. The rate of initial ampicillin hydrolysis was much higher in intact cells of N. gonorrhoeae (TEM-1) than in cells of Escherichia coli K-12 (TEM-1). This suggests that the diffusion rate of ampicillin is much higher in the former organism. The viability of gonococci (TEM-1) was unlike E. coli (TEM-1) affected by low concentrations of ampicillin. However, after complete hydrolysis of ampicillin, viable gonococci (probably bacteriostatic reacting cells) were able to initiate new growth. This heterogeneity of the cell population to penicillin killing is probably one reason why beta-lactamase producing gonococci despite a rather low MIC-value to ampicillin cause infections that are not susceptible to therapy by this agent.

Ampicillin↗

Beta-lactam resistance in clinical isolates of Escherichia coli caused by elevated production of the ampC-mediated chromosomal beta-lactamase.

Among cephalothin-resistant isolates from patients with urinary tract infections, six Escherichia coli strains were found to produce elevated amounts of a beta-lactamase indistinguishable from that coded by the ampC gene of E. coli K-12. The resistance levels displayed by these isolates toward a number of beta-lactams were, for five of them, considerably higher as compared with E. coli K-12 with the same amount of beta-lactamase, implying the importance of intrinsic resistance in these isolates. Cefuroxime, and to a lesser extent cefamandole, were stable to hydrolysis by E. coli chromosomal beta-lactamase but acted as inhibitors of the enzyme. Nevertheless, increased beta-lactamase production mediated an increased resistance toward these drugs. No plasmids were found in the isolates, suggesting a chromosomal location for the respective ampC locus.

Anti-Bacterial Agents↗

Frequency of dividing cells, a new approach to the determination of bacterial growth rates in aquatic environments.

Frequency of dividing cells is suggested to be an indirect measure of the mean growth rate of an aquatic bacterial community. Seasonal changes in frequency of dividing cells were found which covariated with the bacterial uptake of C-labeled phytoplankton exudates. Batch and continuous culture growth experiments, using brackish water bacteria in pure and mixed enrichment cultures, were performed to establish a relationship between frequency of dividing cells and growth rate. An improved technique for bacterial direct counts, using fluorescent staining and epifluorescence microscopy, is presented. Based on a 6-month survey in a coastal area of the Baltic Sea, the bacterial production in the photic zone is estimated. Compared to the total primary production in the area, the bacterial population during this period utilized approximately 25% of the amount of carbon originally fixed by the primary producers.

Journal Article↗

Effect of colony type and pH on surface charge and hydrophobicity of Neisseria gonorrhoeae.

The effect of colonial variation and growth at pH 7.2 or pH 6.0 on the surface properties of Neisseria gonorrhoeae was assessed by the use of two-phase partitioning and hydrophobic interaction chromatography. Cells grown at pH 7.2 tended to be both hydrophobic and to possess a slight negative charge. Growth at pH 6.0 appeared to decrease hydrophobicity and to increase the negative surface charge. Possession of a series of outer membrane proteins, termed the colony opacity-associated proteins, did not appear to significantly affect charge or hydrophobicity. Piliated cells tended to have a higher negative charge than nonpiliated variants. They also tended to be less hydrophobic at pH 7.2, but became more hydrophobic at pH 6.0. The implications of these findings are discussed.

Bacterial Proteins↗

Effect of iron on surface charge and hydrophobicity of Neisseria gonorrhoeae.

The effect of iron concentration during growth on the physicochemical surface properties of the colonial variants of Neisseria gonorrhoeae has been assessed by aqueous two-phase partitioning in a dextran-polyethyleneglycol system containing positively charged trimethylamino-polyethyleneglycol or hydrophobic polyethyleneglycol-palmitate. The complex effects of iron, in combination with other variables known to affect surface charge and hydrophobicity, have provided some clues as to the properties of the gonococcal surface that are important in promoting virulence.

Bacterial Proteins↗

Genetic exchange mechanisms in Neisseria gonorrhoeae.

There are two mechanisms for genetic exchange in Neisseria gonorrhoeae. Plasmid deoxyribonucleic acid can be transferred by conjugation, which is dependent on the presence of a 24.5-megadalton plasmid in the donor cell. We have shown that chromosomal deoxyribonucleic acid can be exchanged between all colonial variants by transformation, but not by conjugation. In the nonpiliated variants, however, this exchange was dependent on the presence of the 24.5-megadalton plasmid in the recipient cell.

Chromosomes, Bacterial↗

Genetic basis for colonial variation in Neisseria gonorrhoeae.

When the piliated colony types of Neisseria gonorrhoeae, which predominate in recent isolates, were nonselectively subcultured in vitro, they gave rise to large numbers of nonpiliated, avirulent colonial variants. Evidence is presented to show that most of this variation occurs after active growth has ceased and that the variation is sensitive to the action of deoxyribonuclease. We suggest that this variation is a result of transformation. A second variation in colonial morphology involved differing levels of "colony opacity-associated proteins" in the outer membrane. This variation was also inhibited by the presence of deoxyribonuclease, but the genetic basis for it is not as yet clear.

Bacterial Proteins↗

In vivo regulation of chromosomal beta-lactamase in Escherichia coli.

Chromosomal beta-lactamase, a periplasmic enzyme of Escherichia coli, was studied with respect to its regulation in vivo. Both the activity and the amount of beta-lactamase increased with growth rate. During a nutritional shift-down, chromosomal beta-lactamase activity followed stable ribonucleic acid accumulation. After a nutritional shift-up the differential rate of beta-lactamase synthesis did not increase immediately (like stable ribonucleic acid), but did increase after a lag period of 30 min. To determine whether beta-lactamase was under stringent control, strains carrying a temperature-sensitive valyl-transfer ribonucleic acid synthetase and differing only in the allelic state of the relA gene were shifted from a permissive to a semipermissive temperature. No influence by the relA gene product was found on beta-lactamase synthesis. The regulation of this periplasmic enzyme is discussed in relation to that of some components of the translational apparatus.

Bacterial Proteins↗

Contribution of a TEM-1-like beta-lactamase to penicillin resistance in Neisseria gonorrhoeae.

Two beta-lactamase-producing strains of Neisseria gonorrhoeae were studied. The substrate profile, molecular weight, and isoelectric point of their beta-lactamases were similar to those of the TEM-1 enzyme produced by many gram-negative bacilli. The gonococcal beta-lactamase was cell bound during exponential growth and was most likely located in the periplasm. Penicillin hydrolysis was efficient in intact cells, suggesting that the cell-bound beta-lactamase was freely accessible to benzylpenicillin. Both beta-lactamase-producing strains of N. gonorrhoeae contained an additional multicopy plasmid with a mass of 3.3 megadaltons (Mdal). A spontaneous penicillin-susceptible revertant lacked both beta-lactamase activity and the 3.3-Mdal plasmid, providing evidence for plasmid-mediated penicillin resistance. During a shift from GC medium to rich MOPS medium, growth of the penicillin-susceptible revertant in contrast to that of the plasmid-carrying strain was markedly impaired, suggesting a physiological effect due to the presence of the 3.3-Mdal plasmid.

DNA, Circular↗

Growth pattern and cell division in Neisseria gonorrhoeae.

The gram-negative coccus Neisseria gonorrhoeae was found to grow regularly in at least two dimensions. Growth proceeded at a linear rate sequentially in each dimension. Growth in the second dimension (former width) was initiated slightly before the pole-division plane distance equalled the cell width. Penicillin treatment localized presumptive growth zones to the existing septum region. It was suggested that new growth zones were always formed perpendicular to the longitudinal axis created in the incipient daughter cells of a dividing coccus. Neither penicillin nor nalidixic acid induced filaments of N. gonorrhoeae. Such structures could nevertheless be formed in the rod-shaped species Neisseria elongata. N. gonorrhoeae divides by septation; however, complete septal structures with separated cytoplasms were rather infrequent. It is proposed that N. gonorrhoeae be regarded as a short rod which always extends parallel to the actual longitudinal axis and which never undergoes a rod-sphere-rod transition.

Cell Division↗

Resistance of Escherichia coli to penicillins: fine-structure mapping and dominance of chromosomal beta-lactamase mutations.

Seven Escherichia coli K-12 mutants with a lowered chromosomal beta-lactamase activity were analyzed genetically. The beta-lactamase-negative mutants isolated from ampA1-carrying strains (resistant to 10 microgram of ampicillin per ml) all carried genetic lesions very close to the ampA1 mutation, which was still present. In an earlier report, two of the mutations mediating a beta-lactamase-negative phenotype (L. G. Burman, T. Park, E. B. Linström, and H. G. Boman, J. Bacteriol. 116:123-130, 1973) were shown to have occurred in the structural gene for beta-lactamase, designated ampC. It is suggested that all beta-lactamase-negative mutants studied here were altered in ampC. The relative order of ampC mutations was (ampC1, ampC8)-ampC9-(ampC12, ampC14)-ampC11, and the gene order was found to be ampC-1mpA-purA. The ampA1 allele was dominant over its wild-type allele but acted only cis and not trans, suggesting that ampA is the promoter or operator region for ampC. A gene dosage effect was found for strains homozygous for ampA+ ampC+ or ampA1 ampC+. Heterozygotes carrying the ampC8 allele on the chromosome showed an apparent derepression of the episomal ampC allele, suggesting a role for beta-lactamase in its own regulation.

Alleles↗