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Biomedical subjects

B Wiedemann

Publications and source records attributed to B Wiedemann.

At least 145 records · Page 8Linked to original sources
PubMed1986

Role of transposition and homologous recombination in the rearrangement of plasmid DNA.

The multi-resistance plasmid pBP16 was used to analyse the variability of R-factors from clinical isolates and the molecular structures and processes involved. The observed rearrangement in pBP16 and its derivatives included inversion, deletion, replicon fusion and dissociation, and transposition. All these events could be traced to the presence and activity of multiple copies of the IS-element IS160 within pBP16. Since IS-elements are common in R-factors, it is likely that they are one of the main reasons for plasmid instability and that they are involved in a major way in plasmid evolution.

DNA Transposable Elements↗
PubMed1986

Insertions of resistance genes into Tn21-like transposons.

The evolution of Tn21 and related multiresistance transposons of natural and artificial origin is described. Variations resulting from insertions and deletions in these transposons indicate the presence of specific recombination sites. There is evidence that these 'hot spots' are flanking several resistance genes. We examined these structures on the basis of the aadA gene, mediating resistance to spectinomycin and streptomycin. Comparison of the DNA sequences of Tn21, Tn7 and pSa indicate the wide spread of these recombination sites.

Base Sequence↗
PubMed1986

Selection of beta-lactamase producers during cephalosporin and penicillin therapy.

Treatment failures due to beta-lactamase producing strains of Enterobacter cloacae, Proteus vulgaris, Citrobacter freundii and Pseudomonas aeruginosa are frequently reported. It is difficult, however, to determine the underlying mechanism of resistance development. Different beta-lactam drugs, such as cephalosporins and penicillins have different ecological impacts on the infections and physiological flora of patients. They select in different ways although the mutation frequency of strains towards beta-lactamase production is not affected by these drugs. Thus in a specific process of selection one has to consider the mechanism and frequency of changes in the beta-lactamase production, the selective power of the different drugs (relation of drug concentration to the MIC for possible mutants or induction of beta-lactamase), selection of resistance in the physiological flora of patients, spread of such mutants to other patients and in the hospital environment, and the stability of beta-lactamase production. As each antibiotic has the potential of selecting mutants and in the case of beta-lactam drugs the more powerful ones select for mutants which produce a beta-lactamase that is more stable against less powerful drugs, a careful selection of drugs together with an effective infection control is mandatory.

Cephalosporins↗
PubMed1985

R1767, an example of the evolution of resistance plasmids.

The Salmonella R-factor system R1767 undergoes frequent rearrangement of its plasmid components. The flux of genetic material within this plasmid system depends on a combination of illegitimate and homologous recombination. The presence of several copies of IS160 and two multiresistance transposons, Tn2410 and Tn2411, are substantial reasons for the observed variations.

Biological Evolution↗
PubMed1985

Tn3 as the molecular basis of ampicillin resistance in E. coli--an epidemiological survey.

Plasmids of 31 E. coli strains coding for the TEM-1 beta-lactamase were analysed for the molecular basis of this enzyme. In transposition experiments we could demonstrate that only 50% of the plasmids were able to transpose their ampicillin-resistance gene. Two of the non-transposing structures were further examined. The 8.1 kb plasmid pBP738 contained Tn3 having suffered a point mutation within the transposase gene that could be complemented by an intact transposase. The 79 kb plasmid pBP749 carried a TEM-1 coding sequence, but the homology with Tn3 was limited to 1.18 kb.

Ampicillin↗
PubMed1985

Characterization of aminoglycoside 6'-N-acetyltransferases [AAC(6')] from gram-negative bacteria and Streptomyces kanamyceticus.

Aminoglycoside-6'-N-acetyltransferase [AAC(6') enzymes] from several Gram-negative bacteria and Streptomyces kanamyceticus were purified by affinity and ion exchange chromatography. The different enzymes were characterized by their biochemical properties including molecular weights, isoelectric points, substrate ranges, and pH-optima. These biochemical characteristics were compared to the data for 6'-N-acetyltransferases from other Gram-negative and Gram-positive bacteria. All data indicated that the group of AAC(6') enzymes is rather heterogeneous from the biochemical point of view and led us to a new proposal for classification of subgroups.

Acetyltransferases↗
PubMed1985

Application of in-vitro models: development of resistance.

The development of chromosomal beta-lactam resistance of Escherichia coli, Enterobacter cloacae and Citrobacter freundii was observed by following the bacterial kill-kinetics in an in-vitro model simulating human serum antibiotic concentrations. From sensitive Escherichia coli cells mutants arose resistant to aminopenicillins, and to first and second generation cephalosporins, whereas with the Ent. cloacae and Citro. freundii mutants were also resistant to cefotaxime. Resistant mutants from all three species could also be selected on antibiotic-containing agar plates. With E. coli they occurred in two steps, the first mutation being stable but the second mutation reverting spontaneously. In Ent. cloacae, and apparently also in Citro. freundii, the mutation changes the cephalosporinase production from an inducible to a constitutive one. The different mutation rates, and the rate was extremely high for some Ent. cloacae strains, were correlated with a corresponding reduction of viable cell count and with the time of re-growth observed in the model.

Anti-Bacterial Agents↗
PubMed1985

The use of bacteria producing the aminoglycoside inactivating enzyme ANT-(2") in an in-vitro model.

A series of transconjugants of Escherichia coli W3110 containing different plasmids coding for the aminoglycoside inactivating enzyme ANT-(2") were tested in an in-vitro model simulating the concentration time curves of aminoglycosides after intramuscular administration of 80 or 120 mg. There was good correlation of the MIC, which ranged from 2 to 32 mg/l, with the killing ability of the drugs. A second dose had no or only little effect on ANT-(2") producing strains. All strains, although of 'intermediate' sensitivity were found to be resistant in the in-vitro model. Only netilmicin could eliminate some of the strains but its activity on ANT-(2")-positive strains was not as good as on ANT-(2")-negative ones.

Aminoglycosides↗
PubMed1985

Evolution of Tn21-related transposons: isolation of Tn2425, which harbours IS161.

The isolation of two multi-resistance transposons, Tn2425 and Tn1831, and their relation to Tn21 and Tn2424, is described. A 1.7 kb segment present in Tn2424 and Tn2425 was identified as an IS element by rec-independent transposition, resulting in a cointegrate structure that carries two direct repeated copies of the IS element. By the isolation of this IS element we demonstrated that transposition is one mechanism leading to sequence variations in Tn21-like structures, especially in the region between the mer operon and the sul gene.

Ampicillin↗
PubMed1985

Evolution of plasmid-coded resistance to broad-spectrum cephalosporins.

A clinical isolate of Klebsiella ozaenae with transferable resistance to broad-spectrum cephalosporins produces a beta-lactamase determined by plasmid pBP60. The beta-lactamase had the same isoelectric point as SHV-1 (7.6). From heteroduplex analysis, an extensive homology between the two bla genes could be deduced; therefore, the new beta-lactamase was designated SHV-2. Enzymatic studies revealed that SHV-2 was able to hydrolyze broad-spectrum cephalosporins due to an increased affinity of these compounds for the enzyme. The assumption that SHV-2 is a natural mutant of SHV-1 was strongly supported by the isolation of a laboratory mutant of SHV-1 that showed activities similar to those of SHV-2.

Cephalosporins↗
PubMed1985

Elimination of plasmids by new 4-quinolones.

Nalidixic acid and six of the new 4-quinolones eliminated F'lac and various native R plasmids from Escherichia coli at one half or one quarter the MIC. Four of eight plasmids tested were cured by all derivatives, with frequencies from 10 to 98%. Quinolones did not eliminate all plasmids that were cured by novobiocin, and vice versa.

Drug Resistance, Microbial↗
PubMed1985

Mechanisms of resistance to beta-lactam antibiotics.

The complex mechanism of resistance towards beta-lactam antibiotics in Gram-negative bacteria can be described by a simple equation in which the hydrolytic activity of the enzyme, the affinity to the penicillin binding protein in competition to the affinity to the beta-lactamase, the quantity of the enzyme and the ability of the drug to penetrate the outer membrane are considered. Depending on the characteristics of the drug, the beta-lactamase, and the microorganisms, the hydrolysis of the drug, its binding, or the reduced penetration can be the predominant factors.

Anti-Bacterial Agents↗
PubMed1984

[The effect of enzymatic modification on lysinoalanine formation in field-bean protein isolate and beta-casein].

Lysinoalanine (LAL) was determined in alkali-treated partial hydrolysates (PH) of casein, peptides isolated from these PH and in PH of field-bean protein to clarify whether intermolecular or intramolecular LAL bridges are preferentially formed. Furthermore, the formation of LAS in plasteins was studied as a contribution to plastein research. The formation of LAL in the peptide mixtures of beta-casein and the decrease of the LAL content in the PH (as compared to intact proteins) indicates that the formation of LAL favours the intramolecular cross-linking of polypeptide chains. The LAL content decreases as the degree of hydrolysis of the PH of the field-bean protein isolate increases, and depends upon the protease used in the production of the hydrolysates. The LAL contents of the alkali-treated plasteins are less than those of the initial hydrolysates. The decrease of the LAL content is directly proportional to the hydrolysis proceeding during the plastein reaction.

Amino Acids↗
PubMed1984

The activity of cefotiam on beta-lactamase-producing bacteria in an in-vitro model.

The activity of cefotiam was tested in an in-vitro model simulating human serum pharmacokinetics. Bacterial strains used for inoculation either produced a penicillinase or a cephalosporinase. The rate of hydrolysis and the MICs of cefotiam were determined in comparison with those of ampicillin and cephalothin. The influence of these beta-lactamases on the killing kinetics and the degradation of cefotiam in the in-vitro model were then measured. Although all beta-lactamases hydrolyzed cefotiam, only the chromosomal cephalosporinases, especially those from Enterobacter and Klebsiella, reduced the elimination of the bacteria by degradation of the drug. A rough correlation between the hydrolytic activity and MIC could be demonstrated for cefotiam but not for ampicillin, while a correlation between killing ability and MIC only existed for strains with cefotiam MICs higher than 16 mg/l.

Ampicillin↗