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Biomedical subjects

D J Zygmunt

Publications and source records attributed to D J Zygmunt.

6 recordsLinked to original sources
PubMed1992

Characterization of four beta-lactamases produced by Staphylococcus aureus.

Staphylococcus aureus produces four types of beta-lactamase (A, B, C, and D). To investigate the effect of specific beta-lactamase type upon staphylococcal resistance, each beta-lactamase was purified to homogeneity, and the Michaelis constants (Km values) and turnover numbers (kcat values) for various penicillin and cephalosporin substrates were determined. Whereas Km values of the four beta-lactamases were comparable for penicillin G, cephalothin, and cefamandole, the type A and D enzymes exhibited greater affinity than the type B and C beta-lactamases for nitrocefin, cefazolin, and cephapirin. Conversely, the type B and C beta-lactamases exhibited greater kcat values than the type A and D enzymes against most of the cephalosporin agents, excluding nitrocefin. In contrast to earlier reports suggesting that the type B beta-lactamase is relatively inefficient in hydrolyzing penicillin G, we found only minor differences in the specific activities and kcat values of the type A, B, and C beta-lactamases. The type D beta-lactamase was distinctly less active against penicillin G, however, exhibiting only 15 to 25% of the kcat values of the other beta-lactamases. More than a 2,000-fold difference between the relative efficiencies of hydrolysis (kcat/Km) of cefazolin and cefuroxime by the type A beta-lactamase exists. This greatly exceeds the 60-fold difference in the stability of penicillin G and cefazolin with the same enzyme. Whereas the isoelectric points of the type A, B, and C beta-lactamases were similar, the value for the type D beta-lactamase was distinguishably lower (10.1 for types A, B, and C and 9.7 for type D). We conclude that marked differences in the stability of commonly used beta-lactams to hydrolysis by the staphylococcal beta-lactamases are present. This heterogeneity and the clinical implication thereof need to be considered in the antibiotic management of staphylococcal infection.

Cephalosporins↗
PubMed1990

Toxoplasma gondii.

Toxoplasmosis encompasses a variety of clinical conditions. Serious sequelae are seen in congenital toxoplasmosis and in infections of the immunocompromised host. In the former, prevention of maternal acquisition of toxoplasmosis during pregnancy is paramount. Infection in the compromised host often presents with neurologic abnormalities. Unfortunately, the HIV syndrome itself or other opportunistic infections can present in a similar manner. Often, empiric treatment for toxoplasmosis is begun based on clinical findings and an enhancing lesion noted on the head CT. Pyrimethamine and sulfadiazine remain the drugs of choice for toxoplasmosis and are able to penetrate blood-brain barriers. Currently, trials using other agents are in progress.

Animals↗
PubMed1990

Strongyloides stercoralis.

In many aspects, S stercoralis is a unique opportunistic pathogen. Via its autoinfections cycle, it is capable of producing both parasitic and bacterial infections at remote organ sites. These infections are often nosocomial. Diagnosis can be very difficult if appropriate microscopic evaluation is not done. Concomitant bacterial infections must be treated with appropriate antimicrobial agents; thiobendazole is the treatment of choice for the parasitic phase of these infections.

Animals↗
PubMed1990

Purification of Staphylococcus aureus beta-lactamases by using sequential cation-exchange and affinity chromatography.

Boronic acids are active-site inhibitors of serine beta-lactamases, and a phenylboronic acid-agarose affinity column has been used to purify beta-lactamase from crude cell extracts of several bacterial species. We applied phenylboronic acid-agarose chromatography to the purification of Staphylococcus aureus beta-lactamase. Two factors interfered with the success of the previously described single-step chromatographic protocol. First, staphylococcal beta-lactamase exhibited non-active-site-mediated adsorption to the agarose used as a support for the meta-aminophenylborate ligand, preventing the recovery of beta-lactamase from the column. Second, the staphylococcal beta-lactamases exhibited low affinity for meta-aminophenylborate with inhibition constants (Kis) ranging from 8.0 x 10(-3) to 20.0 x 10(-3) M. These problems were resolved by modifying the buffers utilized during chromatography and increasing the dimensions of the affinity column, and a two-stage procedure consisting of cation-exchange chromatography followed by affinity chromatography was used to purify each of the four variants of staphylococcal beta-lactamase. The mean specific activities of the purified type A, B, C, and D beta-lactamases were 44.6, 12.2, 10.6, and 30.8 mumol of nitrocefin hydrolyzed per min/mg of protein, respectively. Dimer formation, presumably from intramolecular cysteine-cysteine cross-linking, was observed with the type D beta-lactamase but not with the type A, B, or C enzyme.

Boronic Acids↗