Evidence map›Paper›PMID 40512248›Full record

ArticleEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology2025

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

Anara Babayeva, Bekir Çöl

Abstract read
In one paragraph

Article in European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Anara BabayevaGraduate School of Natural and Applied Sciences, Department of Biology, Muğla Sıtkı Koçman University, Muğla, Turkey.
Bekir ÇölCollege of Sciences, Department of Biology, Division of Biotechnology, Muğla Sıtkı Koçman University, Muğla, Turkey. bcol@mu.edu.tr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe 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.

methodsTo 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.

resultsDisrupted genes included those involved in leucine biosynthesis (leuD), RNA turnover (rnb), tRNA modification (trmU), ubiquinone biosynthesis (ubiG), NAD salvage pathway (pncA), arginine transport (artJ), transcriptional regulator (yddM) and ribosome biogenesis (yhbY), suggesting that epetraborole's primary inhibition of LeuRS synergizes with defects in these pathways. Bioinformatic analyses (Omics Dashboard, DAVID, STRING) linked these genes to tRNA homeostasis, stress response networks, and central dogma processes, implicating tRNA dysregulation as a critical vulnerability under epetraborole-induced stress.

conclusionThis study identifies novel genetic contributors to epetraborole susceptibility and provides a framework for exploring adjuvant therapies or resistance mechanisms to enhance its clinical utility against MDR infections.

Indexed as

Anti-Bacterial AgentsBoron CompoundsEscherichia coliEscherichia coli ProteinsGene Knockout TechniquesGenome, BacterialLeucine-tRNA LigaseMicrobial Sensitivity TestsAnti-Bacterial AgentsBoron CompoundsEscherichia coli ProteinsLeucine-tRNA LigaseAntibiotic resistanceEpetraboroleEscherichia coliGeneKeio collection

Identifiers

PMID40512248
PMCPMC12457515

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