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Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e00014-17. doi: 10.1128/AAC.00014-17. Print 2017 May.

Structural Alteration of OmpR as a Source of Ertapenem Resistance in a CTX-M-15-Producing Escherichia coli O25b:H4 Sequence Type 131 Clinical Isolate.

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Département d'Anesthésie-Réanimation, CHU Amiens-Picardie, and INSERM U1088, Université de Picardie Jules Verne, Amiens, France.
INSERM, IAME, UMR 1137, Paris, France.
Université de Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France.
UMR 8030, CNRS, Université Évry-Val-d'Essonne, CEA, Institut de Génomique-Genoscope, Laboratoire d'Analyses Bioinformatiques pour la Génomique et le Métabolisme and Laboratoire d'Informatique Scientifique, Évry, France.
Institut de Biologie de l'Ecole Normale Supérieure, ENS, CNRS UMR8197, INSERM U1024, Paris, France.
APHP, Hôpital Bichat Claude Bernard, Laboratoire de Génétique Moléculaire, Paris, France.
INSERM, IAME, UMR 1137, Paris, France
APHP, Hôpital Bichat Claude Bernard, Laboratoire de Bactériologie, Paris, France.


In this study, an ertapenem-nonsusceptible Escherichia coli isolate was investigated to determine the genetic basis for its carbapenem resistance phenotype. This clinical strain was recovered from a patient that received, 1 year previously, ertapenem to treat a cholangitis due to a carbapenem-susceptible extended-spectrum-β-lactamase (ESBL)-producing E. coli isolate. Whole-genome sequencing of these strains was performed using Illumina and single-molecule real-time sequencing technologies. It revealed that they belonged to the ST131 clonal group, had the predicted O25b:H4 serotype, and produced the CTX-M-15 and TEM-1 β-lactamases. One nucleotide substitution was identified between these strains. It affected the ompR gene, which codes for a regulatory protein involved in the control of OmpC/OmpF porin expression, creating a Gly-63-Val substitution. The role of OmpR alteration was confirmed by a complementation experiment that fully restored the susceptibility to ertapenem of the clinical isolate. A modeling study showed that the Gly-63-Val change displaced the histidine-kinase phosphorylation site. SDS-PAGE analysis revealed that the ertapenem-nonsusceptible E. coli strain had a decreased expression of OmpC/OmpF porins. No significant defect in the growth rate or in the resistance to Dictyostelium discoideum amoeba phagocytosis was found in the ertapenem-nonsusceptible E. coli isolate compared to its susceptible parental strain. Our report demonstrates for the first time that ertapenem resistance may emerge clinically from ESBL-producing E. coli due to mutations that modulate the OmpR activity.


ESBL; OmpR; ST131; avibactam; carbapenem; envZ; temocillin

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