Article
Role of blaTEM and OmpC in the piperacillin-tazobactam resistance evolution by E. coli in patients with complicated intra-abdominal infection
Author/s | Galvez-Benitez, Lydia
Ortiz de la Rosa, Jose Manuel Rodríguez-Villodres, Angel Casimiro-Soriguer, Carlos S. Molina-Panadero, Irene Alvarez-Marín, Rocío Bonnin, Remy A Naas, Thierry Pachón Díaz, Jerónimo Cisneros, José Miguel Lepe Jiménez, José Antonio Smani, Younes |
Department | Universidad de Sevilla. Departamento de Microbiología Universidad de Sevilla. Departamento de Medicina |
Publication Date | 2023 |
Deposit Date | 2024-05-20 |
Awards | Premio Mensual Publicación Científica Destacada de la US. Facultad de Medicina Premio Anual Publicación Científica Destacada de la US. Facultad de Medicina |
Abstract | Piperacillin-tazobactam resistance (P/T-R) is increasingly reported among Escherichia coli isolates. Although in vitro experiments have suggested that blaTEM gene plays a key role in the P/T-R acquisition, no clinical in ... Piperacillin-tazobactam resistance (P/T-R) is increasingly reported among Escherichia coli isolates. Although in vitro experiments have suggested that blaTEM gene plays a key role in the P/T-R acquisition, no clinical in vivo study has yet confirmed the role of blaTEM 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 blaTEM and other genes associated with P/T-R. Changes in the outer membrane protein (OMP) profile were analyzed using SDS-PAGE, and blaTEM 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 blaTEM gene in P/T-R isolates, generated by three different genetic events: (1) IS26-mediated duplication of the blaTEM gene, (2) generation of a small multicopy plasmid (ColE-like) carrying blaTEM, 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. |
Funding agencies | Economa y Competitividad, Spain Universidad Pablo de Olavide |
Project ID. | CPII20/00018 |
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