Role of blaTEM and OmpC in the piperacillin-tazobactam resistance evolution by E. coli in patients with complicated intra-abdominal infection
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:87 |
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| Enthalten in: |
The Journal of infection - 87(2023), 3 vom: 13. Sept., Seite 220-229 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gálvez-Benítez, Lydia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.08.2023 Date Revised 09.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jinf.2023.07.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359431534 |
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| 245 | 1 | 0 | |a Role of blaTEM and OmpC in the piperacillin-tazobactam resistance evolution by E. coli in patients with complicated intra-abdominal infection |
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Complicated intra-abdominal infection | |
| 650 | 4 | |a Escherichia coli | |
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| 650 | 4 | |a Resistance | |
| 650 | 4 | |a ß-lactamase | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a beta-Lactamases |2 NLM | |
| 650 | 7 | |a EC 3.5.2.6 |2 NLM | |
| 650 | 7 | |a Piperacillin, Tazobactam Drug Combination |2 NLM | |
| 650 | 7 | |a 157044-21-8 |2 NLM | |
| 700 | 1 | |a de la Rosa, José Manuel Ortiz |e verfasserin |4 aut | |
| 700 | 1 | |a Rodriguez-Villodres, Angel |e verfasserin |4 aut | |
| 700 | 1 | |a Casimiro-Soriguer, Carlos S |e verfasserin |4 aut | |
| 700 | 1 | |a Molina-Panadero, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Alvarez-Marin, Rocío |e verfasserin |4 aut | |
| 700 | 1 | |a Bonnin, Rémy A |e verfasserin |4 aut | |
| 700 | 1 | |a Naas, Thierry |e verfasserin |4 aut | |
| 700 | 1 | |a Pachón, Jerónimo |e verfasserin |4 aut | |
| 700 | 1 | |a Cisneros, José Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Lepe, José Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Smani, Younes |e verfasserin |4 aut | |
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