Molecular Signatures of the Eagle Effect Induced by the Artificial Siderophore Conjugate LP-600 in E. coli.

ABSTRACT: Achieving cellular uptake is a central challenge for novel antibiotics targeting Gram-negative bacterial pathogens. One strategy is to hijack the bacterial iron transport system by siderophore-antibiotic conjugates that are actively imported into the cell. This was realized with the MECAM-ampicillin conjugate LP-600 we recently reported that was highly active against E. coli. In the present study, we investigate a paradoxical regrowth of E. coli upon treatment of LP-600 at concentrations 16-32 times above the minimum inhibitory concentration (MIC). The phenomenon, coined "Eagle-effect" in other systems, was not due to resistance formation, and it occurred for the siderophore conjugate but not for free ampicillin. To investigate the molecular imprint of the Eagle effect, a com

SUBMITTER: Lai YH 

PROVIDER: S-EPMC10012262 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature