Evidence map›Paper›PMID 15673760›Full record

ArticleAntimicrobial agents and chemotherapy2005

Discovering the mechanism of action of novel antibacterial agents through transcriptional profiling of conditional mutants.

C Freiberg, H P Fischer, N A Brunner

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 107 citations in OpenAlex.

  1. Review
  2. Perturbation-specific transcriptional mapping for unbiased target elucidation of antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Genetic Approaches to Facilitate Antibacterial Drug Development.Cold Spring Harbor perspectives in medicine · 2015
    Review
  14. Article
  15. Bacterial cytological profiling rapidly identifies the cellular pathways targeted by antibacterial molecules.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
  16. Article
  17. Global analysis of the Staphylococcus aureus response to mupirocin.Antimicrobial agents and chemotherapy · 2012
    Article
  18. Article
  19. Challenges of antibacterial discovery.Clinical microbiology reviews · 2011
    Review
  20. Antibiotics for emerging pathogens.Science (New York, N.Y.) · 2009
    Review
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

3 authors at 2 institutions in 2 countries.

C FreibergBayer HealthCare AG, Pharma Research, 42096 Wuppertal, Germany.
H P Fischer
N A Brunner
Bayer (Germany) · DEGenedata (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We present a new strategy for predicting novel antibiotic mechanisms of action based on the analysis of whole-genome microarray data. We first built up a reference compendium of Bacillus subtilis expression profiles induced by 14 different antibiotics. This data set was expanded by adding expression profiles from mutants that showed downregulation of genes coding for proven or emerging antibacterial targets. Here, we investigate conditional mutants underexpressing ileS, pheST, fabF, and accDA, each of which is essential for growth. Our proof-of-principle analyses reveal that conditional mutants can be used to mimic chemical inhibition of the corresponding gene products. Moreover, we show that a statistical data analysis combined with thorough pathway and regulon analysis can pinpoint the molecular target of uncharacterized antibiotics. We apply this approach to two novel antibiotics: a recently published phenyl-thiazolylurea derivative and the natural product moiramide B. Our results support recent findings suggesting that the phenyl-thiazolylurea derivative is a novel phenylalanyl-tRNA synthetase inhibitor. Finally, we propose a completely novel antibiotic mechanism of action for moiramide B based on inhibition of the bacterial acetyl coenzyme A carboxylase.

Indexed as

Gene Expression ProfilingAlgorithmsAmidesAnti-Bacterial AgentsBacillus subtilisBacteriaDNA, BacterialDNA, ComplementaryEscherichia coliGene Expression Regulation, BacterialGene Expression Regulation, EnzymologicIsoenzymesMicrobial Sensitivity TestsModels, StatisticalMutationOligonucleotide Array Sequence AnalysisAmidesAnti-Bacterial AgentsDNA, BacterialDNA, ComplementaryIsoenzymesmoiramide BRNA, BacterialRNA, MessengerSuccinimides

Identifiers

PMID15673760
PMCPMC547252
OpenAlexW2096630625

What OpenQuestion holds

Textmetadata
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.