Evidence map›Paper›PMID 34297925›Full record

ArticleCell2021

Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis.

Barbara Bosch, Michael A DeJesus, Nicholas C Poulton, Wenzhu Zhang, Curtis A Engelhart, Anisha Zaveri, Sophie Lavalette, Nadine Ruecker, Carolina Trujillo, Joshua B Wallach and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed
14.0field-weighted citation impact, top 1% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

217 citing papers in PubMed, 317 citations in OpenAlex.

  1. Article
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  3. Dual inhibition of respiratory complexes inMicrobiology spectrum · 2026
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  10. Induced alanine auxotrophy as a therapeutic strategy againstbioRxiv : the preprint server for biology · 2026
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  15. CRISPRi-mediatedAntimicrobial agents and chemotherapy · 2026
    Article
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  18. Epigenetic Reprogramming byAntibiotics (Basel, Switzerland) · 2026
    Review
  19. Oligonucleotide genetics forbioRxiv : the preprint server for biology · 2026
    Article
  20. Review

157 more citing papers are in PubMed but not listed here.

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

15 authors at 3 institutions in 1 country.

Barbara BoschLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY 10065, USA.
Michael A DeJesusLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY 10065, USA.
Nicholas C PoultonLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY 10065, USA.
Wenzhu ZhangLaboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA.
Curtis A EngelhartDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Anisha ZaveriDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Sophie LavaletteDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Nadine RueckerDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Carolina TrujilloDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Joshua B WallachDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Shuqi LiLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY 10065, USA.
Sabine EhrtDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
Brian T ChaitLaboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA.
Dirk SchnappingerDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: dis2003@med.cornell.edu.
Jeremy M RockLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address: rock@rockefeller.edu.
Rockefeller University · USWeill Cornell Medicine · USCornell University · US

Funding

TR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular NeighborhoodsP41GM109824 · NIGMS · ROCKEFELLER UNIVERSITY · PI SALI, ANDREJ · 2014 to 2023
$18.8M
National Resource for Mass Spectrom of Biological MacromoleculesP41GM103314 · NIGMS · ROCKEFELLER UNIVERSITY · PI CHAIT, BRIAN T · 2012 to 2017
$9.9M
Towards a molecular understanding of persistent tuberculosis infectionDP2AI144850 · NIAID · ROCKEFELLER UNIVERSITY · PI ROCK, JEREMY MICHAEL · 2018 to 2018
$2.5M
NIAID NIH HHS DP2 AI144850NIGMS NIH HHS P41 GM103314NIGMS NIH HHS P41 GM109824
6 · The paper itself

Abstract

Antibacterial agents target the products of essential genes but rarely achieve complete target inhibition. Thus, the all-or-none definition of essentiality afforded by traditional genetic approaches fails to discern the most attractive bacterial targets: those whose incomplete inhibition results in major fitness costs. In contrast, gene "vulnerability" is a continuous, quantifiable trait that relates the magnitude of gene inhibition to the effect on bacterial fitness. We developed a CRISPR interference-based functional genomics method to systematically titrate gene expression in Mycobacterium tuberculosis (Mtb) and monitor fitness outcomes. We identified highly vulnerable genes in various processes, including novel targets unexplored for drug discovery. Equally important, we identified invulnerable essential genes, potentially explaining failed drug discovery efforts. Comparison of vulnerability between the reference and a hypervirulent Mtb isolate revealed incomplete conservation of vulnerability and that differential vulnerability can predict differential antibacterial susceptibility. Our results quantitatively redefine essential bacterial processes and identify high-value targets for drug development.

Indexed as

Gene Expression Regulation, BacterialGenome, BacterialAmino Acyl-tRNA SynthetasesAntitubercular AgentsBayes TheoremBiological EvolutionClustered Regularly Interspaced Short Palindromic RepeatsGene SilencingMicrobial Sensitivity TestsMycobacterium tuberculosisRNA, Guide, CRISPR-Cas SystemsAmino Acyl-tRNA SynthetasesAntitubercular AgentsRNA, Guide, CRISPR-Cas SystemsBayes TheoremCRISPR-Cas SystemsDrug DevelopmentEssential genesMass SpectrometryMycobacterium smegmatisMycobacterium tuberculosisVulnerability

Identifiers

PMID34297925
PMCPMC8382161
OpenAlexW3184815001

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.