Sub-inhibitory cefsulodin sensitization of E. coli to β-lactams is mediated by PBP1b inhibition
| Autor: | Akash Kumar, Anindya S. Ghosh, Sujoy K. Sarkar, Mouparna Dutta, Dhriti Mallik |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Bacterial Diseases
Penicillin binding proteins Time Factors Antibiotics Drug Evaluation Preclinical medicine.disease_cause Multidisciplinary biology Escherichia coli Proteins Drug Information O Antigens Serine-Type D-Ala-D-Ala Carboxypeptidase Anti-Bacterial Agents Bacterial Pathogens Infectious Diseases Prokaryotic Models Medicine medicine.symptom medicine.drug Research Article Drugs and Devices Gram-negative bacteria Drug Research and Development medicine.drug_class Science Cefsulodin Microbial Sensitivity Tests Microbiology Fluorescence beta-Lactamases Model Organisms Drug Resistance Bacterial medicine Escherichia coli Genetics Humans Penicillin-Binding Proteins Biology biology.organism_classification Penicillin Mechanism of action Mutation Peptidoglycan Glycosyltransferase Bacteria Gene Deletion |
| Zdroj: | PLoS ONE, Vol 7, Iss 11, p e48598 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The combination of antibiotics is one of the strategies to combat drug-resistant bacteria, though only a handful of such combinations are in use, such as the β-lactam combinations. In the present study, the efficacy of a specific sub-inhibitory concentration of cefsulodin with other β-lactams was evaluated against a range of Gram-negative clinical isolates. This approach increased the sensitivity of the isolates, regardless of the β-lactamase production. The preferred target and mechanism of action of cefsulodin were identified in laboratory strains of Escherichia coli, by examining the effects of deleting the penicillin-binding protein (PBP) 1a and 1b encoding genes individually. Deletion of PBP1b was involved in sensitizing the bacteria to β-lactam agents, irrespective of its O-antigen status. Moreover, the use of a sub-inhibitory concentration of cefsulodin in combination with a β-lactam exerted an effect similar to that one obtained for PBP1b gene deletion. We conclude that the identified β-lactam/cefsulodin combination works by inhibiting PBP1b (at least partially) despite the involvement of β-lactamases, and therefore could be extended to a broad range of Gram-negative pathogens. |
| Databáze: | OpenAIRE |
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