A γ-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli

Abstract

Treatment of multidrug resistant Gram-negative (Gr-) bacterial pathogens represent a critical clinical need. Here we report on a novel γ -lactam pyrazolidinone that targets penicillin binding protein (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1, are reported along with the finding that 1 is resistant to hydrolysis by all four classes of β-lactamases. The drug-like characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3.