PER-14, a β-lactamase variant with reduced sensitivity to avibactam and relebactam

Abstract

PER-1-producing Pseudomonas and Acinetobacter and PER-2-producingEnterobacterales, respectively, are increasingly difficult to treat due to combinedresistance to antibiotics like ceftazidime, cefiderocol, and ceftazidime/aztreonam-avibactam, among others. PER-14 differs from PER-2 by an S130T substitution. Throughcombined functional and in silico analyses, we demonstrated that PER-14 is resistant toavibactam and relebactam inhibition while retaining an extended-spectrum activity andthe ability to hydrolyze cefiderocol, as the S130T substitution affects the proper bindingof the DBOs.