Evidence map›Paper›PMID 22840772›Full record

ArticleChemistry & biology2012

Pathway-selective sensitization of Mycobacterium tuberculosis for target-based whole-cell screening.

Garth L Abrahams, Anuradha Kumar, Suzana Savvi, Alvin W Hung, Shijun Wen, Chris Abell, Clifton E Barry, David R Sherman, Helena I M Boshoff, Valerie Mizrahi

Abstract read
In one paragraph

Article in Chemistry & biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

77 citing papers in PubMed, 132 citations in OpenAlex.

  1. The Spermidine Synthase Gene as a Reporter of Transcription Inhibition inInternational journal of molecular sciences · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Metabolic Rewiring ofMetabolites · 2024
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Chemical Validation ofAngewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023
    Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

17 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

10 authors at 4 institutions in 3 countries.

Garth L AbrahamsMolecular Mycobacteriology Research Unit and DST/NRF Centre of Excellence for Biomedical TB Research, University of the Witwatersrand and the National Health Laboratory Service, Johannesburg 2000, South Africa. garth.abrahams@uct.ac.za
Anuradha Kumar
Suzana Savvi
Alvin W Hung
Shijun Wen
Chris Abell
Clifton E Barry
David R Sherman
Helena I M Boshoff
Valerie Mizrahi
National Health Laboratory Service · ZAUniversity of Cambridge · GBCenter for Infectious Disease Research · USNational Institutes of Health · US

Funding

Development Of New Chemotherapeutics For TuberculosisZIAAI000693 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2025
$20.1M
Exploring the metabolism of non-replicating and drug-resistant TBZIAAI000783 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2017
$8.2M
Intramural NIH HHS ZIA AI000693
6 · The paper itself

Abstract

Whole-cell screening of Mycobacterium tuberculosis (Mtb) remains a mainstay of drug discovery, but subsequent target elucidation often proves difficult. Conditional mutants that underexpress essential genes have been used to identify compounds with known mechanism of action by target-based whole-cell screening (TB-WCS). Here, the feasibility of TB-WCS in Mtb was assessed by generating mutants that conditionally express pantothenate synthetase (panC), diaminopimelate decarboxylase (lysA), and isocitrate lyase (icl1). The essentiality of panC and lysA, and conditional essentiality of icl1 for growth on fatty acids, was confirmed. Depletion of PanC and Icl1 rendered mutants hypersensitive to target-specific inhibitors. Stable reporter strains were generated for use in high-throughput screening, and their utility was demonstrated by identifying compounds that display greater potency against a PanC-depleted strain. These findings illustrate the power of TB-WCS as a tool for tuberculosis drug discovery.

Indexed as

Bacterial ProteinsCarboxy-LyasesDose-Response Relationship, DrugDrug DiscoveryHigh-Throughput Screening AssaysIsocitrate LyaseMycobacterium tuberculosisPeptide SynthasesSmall Molecule LibrariesStructure-Activity RelationshipBacterial ProteinsCarboxy-LyasesIsocitrate LyaseLysA protein, Mycobacterium tuberculosispantothenate synthetasePeptide SynthasesSmall Molecule Libraries

Identifiers

PMID22840772
PMCPMC3421836
OpenAlexW2064939702

What OpenQuestion holds

Textmetadata
LicenceTDM
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.