New Cephamycin Antibiotic, CS-1170: Binding Affinity to Penicillin-Binding Proteins and Inhibition of Peptidoglycan Cross-Linking Reactions in Escherichia coli
| Autor: | Satoshi Ohya, Shigeo Tamaki, Shinichi Sugawara, Michio Matsuhashi, Mitsuo Yamazaki |
|---|---|
| Rok vydání: | 1978 |
| Předmět: |
Penicillin binding proteins
Biosynthesis Chemistry Mechanisms of Action and Resistance Penicillins Peptidoglycan medicine.disease_cause Binding Competitive chemistry.chemical_compound Minimum inhibitory concentration Bacterial Proteins Escherichia coli polycyclic compounds medicine Pharmacology (medical) Mecillinam Cephamycins Pharmacology biology Amdinocillin Membrane Proteins Drug Synergism Penicillin G biochemical phenomena metabolism and nutrition Carboxypeptidase Cephalosporins Penicillin Infectious Diseases chemistry Biochemistry biology.protein bacteria Carrier Proteins Cephamycin Protein Binding medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 14:780-785 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.14.5.780 |
| Popis: | The binding activity of CS-1170, a new cephamycin antibiotic, to penicillin-binding proteins (PBPs) in Escherichia coli and Proteus species and the potency of this antibiotic in vitro to inhibit enzymes involved in peptidoglycan cross-linking in E. coli were tested. Similar experiments were carried out with the 7α-H analog of CS-1170, R-45656, and the results were compared with those obtained with CS-1170. CS-1170 showed high affinities (compared with that of penicillin G) for E. coli PBP-1A, -1Bs, and -3, the PBPs of higher molecular weight, but not PBP-2. It also inhibited the in vitro peptidoglycan cross linking reaction and concomitant release of d -alanine at very low concentrations (approximately its minimal inhibitory concentration). This antibiotic also showed very high affinity for PBP-4, -5, and -6, the PBPs of lower molecular weight, and at extremely low concentrations it inhibited d -alanine carboxypeptidases IA and IB, corresponding to PBP-5/6 and PBP-4, respectively. CS-1170 seemed to be resistant to the β-lactamase activity of PBP-5 and -6 in E. coli and Proteus species. R-45656 showed as high an affinity for PBP-1A, -1Bs, and -3 as CS-1170, but unlike CS-1170, it had low affinities for PBP-4, -5, and -6. The concentrations of R-45656 required for inhibition of d -alanine carboxypeptidases IA and IB were also much higher than those of CS-1170. R-45656 showed rather low activities in inhibiting the in vitro cross-linking reaction of peptidoglycan and concomitant release of d -alanine. Synergism was observed in 9 of 22 strains examined between CS-1170 and mecillinam, which bound specifically to PBP-2. |
| Databáze: | OpenAIRE |
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