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Biomedical subjects

R Labia

Publications and source records attributed to R Labia.

At least 145 records · Page 8Linked to original sources
PubMed1985

Binding of latamoxef (moxalactam) and its decarboxylated derivative to Escherichia coli and Pseudomonas aeruginosa penicillin-binding proteins.

The binding of latamoxef (moxalactam) and of a decarboxylated derivative to Escherichia coli and Pseudomonas aeruginosa penicillin-binding proteins (PBPs) was measured by competition experiments with 125I-radiolabelled penicillin X. Latamoxef and the decarboxylated derivative were highly bound to most of the PBPs, with the exception of PBP-2. As the two compounds possess a phenolic side-chain, they also could be radiolabelled with 125I. The proteins thus labelled by these derivatives were qualitatively the same as those labelled by 125I-penicillin X, except for PBP-2 which was not labelled by the iodo derivatives of latamoxef and its decarboxylated derivative, and PBP-1c (in E. coli) which is labelled only poorly by the radioactive penicillin. No important difference between latamoxef and its decarboxylated derivative was found, and the same observation was made for penicillin G and carbenicillin. Thus, it was concluded that the carboxylic group of latamoxef does not play an important role in affinity for the targets.

Bacterial Proteins↗
PubMed1985

Behaviour of cefmenoxime towards beta-lactamases.

Using several well-characterized beta-lactamases isolated from Gram-negative bacteria, the interactions of cefmenoxime, a new methoxy-imino-amino-2-thiazol cephalosporin were compared with those of cefotaxime, lamoxactam, cefoperazone and ceftazidime. On-line computerized microacidimetry allowed determination of the affinity of these compounds for the enzymes, which was characterized by Ki values. Microacidimetry showed poor interactions of cefmenoxime with penicillinase TEM-1 (low Vm, poor affinity) whereas it showed a high affinity for the cephalosporinases, as is also the case for cefotaxime or lamoxactam. Both cefmenoxime and cefotaxime showed relative susceptibility in Masuda's double disc technique.

Cefmenoxime↗
PubMed1984

Affinity of cefmenoxime for beta-lactamases: an analysis.

The interactions of cefmenoxime with beta-lactamases in comparison with cefotaxime, moxalactam, cefoperazone, and ceftazidime have been determined. On-line computerized microacidimetry allowed determination of the affinity of these compounds with the enzymes, which was characterized by Km values. The beta-lactamases that were used were two cephalosporinases and one penicillinase. Within these data, the cephalosporins could be classified into three groups: (1) those with high affinity for the cephalosporinases and very poor affinity for the penicillinase (cefmenoxime, cefotaxime, and moxalactam); (2) those with moderate affinity for the cephalosporinases and very poor affinity for the penicillinase (ceftazidime); (3) those with poor affinity for all enzymes (cefoperazone). In the case of the penicillinase (TEM-1), only cefoperazone was subject to some hydrolysis.

Bacteria↗
PubMed1984

[Mechanisms of azlocillin resistance in Pseudomonas aeruginosa].

The authors have evaluated the susceptibility of azlocillin to beta-lactamases habitually produced by Pseudomonas aeruginosa, i.e. TEM and CARB types penicillinases and the so-called Sabath and Abraham cephalosporinase. As all penicillins, azlocillin is liable to hydrolysis by penicillinases that also affect, through to a lesser extent, some cephalosporin. It is also degraded, albeit moderately by the Sabath and Abraham cephalosporinase. The authors have also compared the behaviour of azlocillin towards beta-lactamases to that of other beta-lactam antibiotics, notably carbenicillin, cefoperazone and cefsulodin.

Azlocillin↗
PubMed1984

The action of beta-lactamases on desacetyl-cefotaxime and cefotaxime.

Desacetyl-cefotaxime is the main cefotaxime metabolite. Its antibacterial activity is less than that of the parent molecule, but the combination of cefotaxime and desacetyl-cefotaxime is often synergistic. We analysed the hydrolysis of desacetyl-cefotaxime, in comparison with cefotaxime, by 10 beta-lactamases, mostly cephalosporinases, isolated from various Gram-negative species. From partially purified beta-lactamase preparations of high specific activity, we determined the maximum rates of hydrolysis (Vm) and the Michaelis constants (Ki and Km when possible). It appeared for 7 beta-lactamases the rate of desacetyl-cefotaxime hydrolysis was 2.1 times greater than that of cefotaxime, in terms of geometrical mean value, but with 3 enzymes no hydrolysis was shown for one compound. For 8 enzymes, the Ki, and sometimes Km, of desacetyl cefotaxime are 39 times higher than those of cefotaxime (geometric mean value), which corresponds to a lower affinity.

Cefotaxime↗
PubMed1984

Affinity of temocillin for Escherichia coli K-12 penicillin-binding proteins.

Temocillin is a 6 alpha-methoxy penicillin which shows poor affinity for the penicillin-binding proteins (PBPs) of Escherichia coli K-12 when tested by competition with [14C]penicillin G or [125I]penicillin X. When the reaction conditions for the radiolabeled penicillin used in this procedure were modified by lowering the temperature (2 degrees C) and reducing the incubation time (3 min), temocillin showed a much higher affinity for PBP-3 and improved affinity for the other PBPs, with the exception of PBP-2. Direct labeling procedures with [14C]temocillin also showed that the compound had affinity for PBPs 1a and 3. These results are more consistent with the effects of temocillin on the morphology of E. coli than the poor affinity values obtained by the classical competitive procedure. Reasons for the disparity between these assay systems are discussed.

Anti-Bacterial Agents↗
PubMed1984

[HPLC study of the inhibition of enterobacterial cephalosporinases by cefmenoxime].

High performance liquid chromatography (HPLC) has shown that cefmenoxime and cefotaxime are stable to the cephalosporinase of Enterobacter cloacae P99 , Morganella morganii GN 1510 and Serratia liquefaciens 132. They are significantly resistant to hydrolysis by 100 cephalosporinase units (cephalosporinase production of 10(12) bacterial). Cefmenoxime and cefotaxime are also inhibitors of cephalosporinase at the concentration of 5.10-10 micrograms per 10-10 unit of enzyme.

Cefmenoxime↗
PubMed1983

[Moxalactam: an inactivator of beta-lactamases].

At present, Moxalactam is the beta-lactam antibiotic which shows the greatest resistance to beta-lactamases. Moxalactam has little, if any, interactions with penicillinases, as is also the case of cefoxitin, cefuroxime and cefotaxime. Resistance of Moxalactam to cephalosporinases, however, appears to be related to the unique property of inactivating them. This implies: a specific process which involves the active site of the enzymes; a progressive, or time-dependent, process, which progressively abolishes beta-lactamase activity. This process was observed with most of the tested cephalosporinases. Thus, Moxalactam is the first beta-lactam antibiotic which inactivates beta-lactamases. This is probably why Moxalactam is so resistant to the action of beta-lactamases.

Cephalosporinase↗
PubMed1983

Synthesis of a 125I-radiolabeled penicillin for penicillin-binding proteins studies.

Radioiodination of penicillin X (p-hydroxybenzylpenicillin) with 125INa, using the chloramine-T method, is simple and almost quantitative. The product thus obtained can be used without further purification for the penicillin-binding proteins (PBPs) assay. The chemical structure of 125I-penicillin X is very close to that of penicillin G, and the affinity of the two compounds for the PBPs are very similar. 125I-penicillin X can then advantageously replace [14C]penicillin G in these experiments, as its specific radioactivity is 2000 Ci/mol, in our preparations, instead of about 50 Ci/mol; thus, the experimental procedure is simplified and the autoradiography exposure time is reduced to 12-48 h.

Autoradiography↗
PubMed1983

Cefotetan and beta-lactamases. I. An analysis of the affinity of cefotetan for beta-lactamases.

Cefotetan is a new cephamycin whose interaction with a group of eight beta-lactamases isolated from various Gram-negative bacteria has been studied. Using computerized micro-acidimetry, cefotetan was found to be resistant to the hydrolytic action of various enzymes, including those which actively hydrolyse cefotaxime. Despite this resistance to hydrolysis, cefotetan nevertheless shows a certain affinity for these enzymes. These data were submitted to two statistical procedures consisting of correspondence analysis and ascending hierarchical classification. These techniques revealed that cefotetan behaves very much like cefoxitin (another cephamycin) and also like cefotaxime and moxalactam.

Anti-Bacterial Agents↗
PubMed1983

Cefotetan and beta-lactamases. II. An unusual property: the inactivation of some beta-lactamases by cefotetan.

Initially, cefotetan interacts with beta-lactamases to form a classical Michaelis complex characterized by a term Ki (the inhibition constant). In a second phase, this complex develops with time to form a new entity devoid of enzymic activity. This new entity may have the structure of an acyl enzyme with variable stability. In the case of TEM-1 and TEM-2 beta-lactamases, the process is progressively and totally reversible. The same phenomena were observed in varying degrees for Pitton's type 2 (PIT-2) penicillinase, OXA-1 and CARB-1. The Klebsiella oxytoca and Proteus vulgaris beta-lactamases are also inactivated by this same process. However, four other cephalosporinases appear to be unaffected by this mechanism.

Anti-Bacterial Agents↗
PubMed1982

[Mezlocillin and beta-lactamases (author's transl)].

Like all penicillins, mezlocillin is degraded by beta-lactamases of the penicillinase type. It is also degraded to some extent by beta-lactamases of the cephalosporinase type. Yet in both cases mezlocillin behaves approximately like the first and second generation cephalosporins. This, together with good intrinsic activity, accounts for the valuable antibacterial properties of the antibiotic, particularly against Enterobacteriacaea.

Cephalosporinase↗
PubMed1980

Inhibition kinetics of three R-factor-mediated beta-lactamases by a new beta-lactam sulfone (CP 45899).

A new beta-lactam sulfone, CP 45899, has been proved to be a time-dependent irreversible inhibitor of three R-factor-mediated beta-lactamases (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6): TEM-1 (pI = 5.4), TEM-2 (pI = 5.6) and Pitton's type 2 (pI = 7.7). This inhibition occurs in two principal steps: (1) formation of a reversible enzyme-inhibitor complex (characterized by a Ki); (2) evolution of this complex into one, or more, inactive protein(s) (kinact). With the three beta-lactamases CP 45899 shows, respectively, Ki of 0.9, 0.8 and 1.8 microM and kinact of 1.2 . 10(-3), 0.8 . 10(-3) and 1 . 10(-3) s-1; the turnover numbers are: 525, 2280 and 1220. These results are compared to those previously obtained with clavulanic acid.

Escherichia coli↗