Evidence map›Paper›PMID 39541213›Full record

ArticleCell reports2024

Rationally designed pooled CRISPRi-seq uncovers an inhibitor of bacterial peptidyl-tRNA hydrolase.

A S M Zisanur Rahman, Egor A Syroegin, Julieta Novomisky Nechcoff, Archit Devarajan, Yury S Polikanov, Silvia T Cardona

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2024. 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

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

A S M Zisanur RahmanDepartment of Microbiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Egor A SyroeginDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Julieta Novomisky NechcoffDepartment of Microbiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Archit DevarajanDepartment of Microbiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Yury S PolikanovDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA; Center for Biomolecular Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA; Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Silvia T CardonaDepartment of Microbiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. Electronic address: silvia.cardona@umanitoba.ca.

Funding

Molecular mechanisms of action of ribosome-targeting antibiotics.R01GM132302 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI POLIKANOV, YURY · 2019 to 2022
$1.3M
Structural basis of Cfr-mediated resistance to antibiotics targeting the bacterial ribosomeR21AI163466 · NIAID · UNIVERSITY OF ILLINOIS AT CHICAGO · PI POLIKANOV, YURY · 2021 to 2022
$426k
NIAID NIH HHS R21 AI163466NIGMS NIH HHS R01 GM132302
6 · The paper itself

Abstract

Bacterial mutant libraries with downregulated antibiotic targets are useful tools for elucidating the mechanisms of action of antibacterial compounds, a pivotal step in antibiotic discovery. However, achieving genomic coverage of antibacterial targets poses a challenge due to the uneven proliferation of knockdown mutants during pooled growth, leading to the unintended loss of important targets. To overcome this issue, we constructed an arrayed essential gene mutant library (EGML) in the antibiotic-resistant bacterium Burkholderia cenocepacia using CRISPR interference (CRISPRi). By modeling depletion levels and adjusting knockdown mutant inocula, we rationally designed and optimized a CRISPR interference-mediated pooled library of essential genes (CIMPLE) approaching coverage of the bacterial essential genome with mutant sensitization. We exposed CIMPLE to an uncharacterized bacterial growth inhibitor structurally different from antibiotics and discovered that it inhibits the essential peptidyl-tRNA hydrolase. Overall, CIMPLE leverages the advantages of arrayed and pooled CRISPRi libraries to uncover unexplored targets for antibiotic action.

Indexed as

Carboxylic Ester HydrolasesAnti-Bacterial AgentsBacterial ProteinsBurkholderia cenocepaciaClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsEnzyme InhibitorsGene LibraryGenes, EssentialMutationaminoacyl-tRNA hydrolaseAnti-Bacterial AgentsBacterial ProteinsCarboxylic Ester HydrolasesEnzyme Inhibitorsantibiotic mechanisms of actionarrayed libraryCP: MicrobiologyCRISPRiCRISPRi-seqessential genespeptidyl-tRNA hydrolasepooled libraryPthribosome-associated quality control

Identifiers

PMID39541213
PMCPMC12399363

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.