Overproduction of a Metallo-β-Lactamase by a Strong Promoter Causes High-Level Imipenem Resistance in a Clinical Isolate of Pseudomonas aeruginosa
| Autor: | Toru Nakai, Kazuo Hatano, Shinobu Takeda, Fumiaki Ikeda |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Pharmacology
Imipenem Pseudomonas aeruginosa Chemistry medicine.medical_treatment General Medicine Drug resistance biochemical phenomena metabolism and nutrition bacterial infections and mycoses medicine.disease_cause Microbiology Bacterial genetics Infectious Diseases Antibiotic resistance Oncology Drug Discovery β lactams polycyclic compounds Beta-lactamase medicine bacteria Pharmacology (medical) Overproduction medicine.drug |
| Zdroj: | Chemotherapy. 54:181-187 |
| ISSN: | 1421-9794 0009-3157 |
| DOI: | 10.1159/000140362 |
| Popis: | Background: Metallo-β-lactamase is one of the feared resistance mechanisms inPseudomonas aeruginosa. Methods: β-Lactamase activity was determined using crude enzymes. Cloned plasmids were transformed in P. aeruginosa KG2505, PAO1 derivative without an AmpC β-lactamase and a MexAB-OprM efflux pump. Results:P. aeruginosa No. 20232 was highly resistant to imipenem (minimum inhibitory concentration >512 µg/ml). It possessed IMP-10 and the activity was 1.89 ± 0.42 µmol/min/mg of protein, which was 5–8 times higher than other tested isolates. The blaIMP-10 promoter was strong (–35 region, TTGACA; –10 region, TAAACT); on the other hand, blaIMP of other isolates had a hybrid promoter. Transformants with plasmid encoding blaIMP-10 with a strong promoter had higher enzymatic activity and were less susceptible to imipenem than those encoding blaIMP-10 with a hybrid promoter. Conclusions: The high metallo-β-lactamase activity caused by a strong promoter was a major determinant for high-level imipenem resistance of P. aeruginosa No. 20232. |
| Databáze: | OpenAIRE |
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