In vitro evolution of durlobactam resistance in NDM-producing Escherichia coli due to a single mutation in mrdA...

Durlobactam, a diazabicyclooctane β-lactamase inhibitor, exhibits direct antibacterial activity by binding to penicillin-binding protein 2 (PBP2). We generated a mutant strain of New Delhi metallo-β-lactamase-producing Escherichia coli with a durlobactam minimum inhibitory concentration of 2 µg/mL, representing a 16-fold increase from baseline, by exposing it to increasing concentrations of durlobactam. Resistance was attributed to a point mutation in the mrdA gene, resulting in a V522I substitution in PBP2.