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Título: | Role of blaTEM and OmpC in the piperacillin-tazobactam resistance evolution by E. coli in patients with complicated intra-abdominal infection |
Autor: | Gálvez-Benítez, Lydia CSIC ORCID; Ortiz de la Rosa, José Manuel CSIC ORCID; Rodríguez-Villodres, Ángel CSIC ORCID; Casimiro-Soriguer, Carlos S. CSIC ORCID CVN; Molino Panadero, I; Álvarez-Marín, Rocío CSIC ORCID; Bonnin, Rémy A.; Naas, Thierry; Pachón, Jerónimo CSIC ORCID; Cisneros, José Miguel CSIC ORCID; Lepe, José A. CSIC ORCID; Smani, Younes CSIC ORCID | Palabras clave: | Escherichia coli ß-lactamase OmpC Piperacillin-tazobactam Resistance Complicated intra-abdominal infection |
Fecha de publicación: | sep-2023 | Editor: | Elsevier | Citación: | Journal of Infection 87(3): 220-229 (2023) | Resumen: | Piperacillin-tazobactam resistance (P/T-R) is increasingly reported among Escherichia coli isolates. Although in vitro experiments have suggested that bla gene plays a key role in the P/T-R acquisition, no clinical in vivo study has yet confirmed the role of bla or other genes. Therefore, we aimed to identify the mechanisms underlying P/T-R by following up patients with E. coli complicated intra-abdominal infections (cIAI) who experienced P/T treatment failure. Four pairs of strains, clonally related from four patients, were isolated both before and after treatment with P/T dosed at 4 g/0.5 g intravenously. The P/T MIC was tested using broth microdilution, and β-lactamase activity was determined in these isolates. Whole-genome sequencing (WGS) was performed to decipher the role of bla and other genes associated with P/T-R. Changes in the outer membrane protein (OMP) profile were analyzed using SDS-PAGE, and bla and ompC transcription levels were measured by RT-qPCR. In addition, in vitro competition fitness was performed between each pairs of strains (P/T-susceptible vs. P/T-resistant). We found a higher copy number of bla gene in P/T-R isolates, generated by three different genetic events: (1) IS26-mediated duplication of the bla gene, (2) generation of a small multicopy plasmid (ColE-like) carrying bla, and (3) adaptive evolution via reduction of plasmid size, leading to a higher plasmid copy number. Moreover, two P/T-R strains showed reduced expression of OmpC. This study describes the mechanisms involved in the acquisition of P/T-R by E. coli in patients with cIAI. The understanding of P/T-R evolution is crucial for effectively treating infected patients and preventing the spread of resistant microorganisms. | Versión del editor: | http://dx.doi.org/10.1016/j.jinf.2023.07.005 | URI: | http://hdl.handle.net/10261/341910 | DOI: | 10.1016/j.jinf.2023.07.005 | Identificadores: | issn: 0163-4453 e-issn: 1532-2742 |
Aparece en las colecciones: | (CABD) Artículos (IBIS) Artículos |
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Role of blaTEM_Gálvez_PV_Art2023.pdf | 4,36 MB | Adobe PDF | Visualizar/Abrir |
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