Biochemical characterization of the acquired metallo-beta-lactamase SPM-1 from Pseudomonas aeruginosa
| Autor: | Timothy R. Walsh, Mark Toleman, Tanya A. Murphy, Ronald N. Jones, Alan M. Simm |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Carbapenem
Stereochemistry medicine.drug_class Cephalosporin Biology medicine.disease_cause beta-Lactams beta-Lactamases chemistry.chemical_compound Mechanisms of Resistance medicine polycyclic compounds Pharmacology (medical) Amino Acid Sequence Pharmacology Pseudomonas aeruginosa fungi biochemical phenomena metabolism and nutrition Dipicolinic acid biology.organism_classification bacterial infections and mycoses Anti-Bacterial Agents Penicillin Infectious Diseases chemistry Biochemistry Pseudomonadales bacteria Bacteria Pseudomonadaceae medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 47(2) |
| ISSN: | 0066-4804 |
| Popis: | SPM-1 is a new metallo-β-lactamase recently identified in Pseudomonas aeruginosa strain 48-1997A, isolated in Sao Paulo, Brazil. Kinetic analysis demonstrated that SPM-1 has a broad hydrolytic profile across a wide range of β-lactam antibiotics. Considerable variation was observed within the penicillin, cephalosporin, and carbapenem subfamilies; however, on the whole, SPM-1 appears to preferentially hydrolyze cephalosporins. The highest k cat/ K m ratios (in micromolar per second) overall were observed for this subgroup. The hydrolytic profile of SPM-1 bears the most similarity to that of the metallo-β-lactamase IMP-1, yet for the most part, SPM-1 has k cat / K m values higher than those of IMP-1. Zinc chelator studies established that progressive inhibition of SPM-1 by EDTA, dipicolinic acid, and 1-10- o -phenanthroline demonstrated a biexponential pattern in which none of the chelators completely inhibited SPM-1. A homology model of SPM-1 was developed on the basis of the IMP-1 crystal structure, which showed the protein folding and active-site structure characteristic of metallo-β-lactamases and which provides an explanation for the kinetic profiles observed. |
| Databáze: | OpenAIRE |
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