Genome-wide Screening of the Escherichia coli Keio Knockout Collection Identifies Genetic Determinants of Epetraborole Hypersusceptibility.

ABSTRACT:

Purpose

The escalating threat of antibiotic resistance necessitates innovative strategies to enhance the efficacy of emerging antimicrobials. Epetraborole (EP) is a boron-containing antibiotic targeting leucyl-tRNA synthetase (LeuRS) and has attracted interest for its novel mechanism of action and potential to treat infections caused by multidrug-resistant (MDR) Gram-negative pathogens.

Methods

To elucidate the genetic determinants of EP susceptibility, we conducted a genome-wide screen (GWS) of the Escherichia coli Keio knockout collection, which comprises ~4,000 single-gene deletion mutants. Mutants exhibiting increased susceptibility to epetraborole were identified and validated via complementation assays.

Results

Disrupted genes included those involved in leucine

SUBMITTER: Babayeva A 

PROVIDER: S-EPMC12457515 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature