Activity of carbapenem BMS-181139 against Pseudomonas aeruginosa is not dependent on porin protein D2
| Autor: | B Kolek, Elizabeth Gradelski, R E Kessler, Michael J. Pucci, D P Bonner, Joan Fung-Tomc, Beatrice Minassian |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Carbapenem
Imipenem Porins Muramoylpentapeptide Carboxypeptidase Biology medicine.disease_cause Guanidines Meropenem beta-Lactamases Microbiology Bacterial Proteins polycyclic compounds medicine Penicillin-Binding Proteins Pharmacology (medical) Amino Acids Biapenem Cross-resistance Antibacterial agent Pharmacology Pseudomonas aeruginosa Panipenem digestive oral and skin physiology Drug Resistance Microbial biochemical phenomena metabolism and nutrition bacterial infections and mycoses stomatognathic diseases Infectious Diseases Carbapenems Hexosyltransferases Peptidyl Transferases Carrier Proteins Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 39:386-393 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.39.2.386 |
| Popis: | The broad antipseudomonal spectrum of the carbapenem BMS-181139 includes clinical strains and laboratory mutants of Pseudomonas aeruginosa that are resistant to imipenem. Unlike other known carbapenems (meropenem, panipenem, biapenem, and BO-2727), which have reduced activity against imipenem-resistant strains of P. aeruginosa, BMS-181139 was equally active against imipenem-susceptible (D2-sufficient) and imipenem-resistant (D2-deficient) strains. Conversely, imipenem and meropenem activities were the same against the susceptible parental strains and their BMS-181139-resistant mutants. Whereas basic amino acids antagonized the antipseudomonal activities of imipenem and meropenem, they had no effect on the activity of BMS-181139. These results suggest that the uptake of BMS-181139 into pseudomonal cells occurs by a non-D2 pathway. Compared with imipenem and meropenem, BMS-181139 may have a slightly higher affinity for penicillin-binding protein 2 (PBP-2) of P. aeruginosa. The rates of resistance development to imipenem, meropenem, and BMS-181139 in P. aeruginosa strains were similar; resistance occurred at frequencies of approximately 10(-7) to 10(-8). Resistance to BMS-181139 in P. aeruginosa is presumed to be caused by its diminished permeability since no change in their penicillin-binding protein affinities or beta-lactamase levels could be detected. In summary, BMS-181139 is a new carbapenem which differs from other known carbapenems in its lack of cross-resistance with imipenem. This difference could be explained by the permeation of BMS-181139 through a non-D2 channel, compared to the preferential uptake of other carbapenems by the D2 porin. |
| Databáze: | OpenAIRE |
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