PBT2 potentiates carbapenem antibiotics against diverse Klebsiella pneumoniae strains.

Abstract

UNLABELLED: Carbapenem-resistant Klebsiella pneumoniae is recognized by the World Health Organization as a critical priority for urgent antimicrobial development. Due to the lack of novel antimicrobial classes in the development pipeline, this study investigated the application of an antibiotic potentiator, the zinc ionophore PBT2, to restore the utility of critical antibiotics. The data show that zinc and PBT2 can increase the sensitivity of diverse clinical strains of K. pneumoniae to carbapenem antibiotics, including those strains containing metallo-β-lactamases and porin mutations. PBT2 induced zinc and iron dyshomeostasis in these strains, resulting in altered uptake of multiple antimic..