Evidence map›Paper›PMID 24687489›Full record

ArticleAntimicrobial agents and chemotherapy2014

Discovery of novel cell wall-active compounds using P ywaC, a sensitive reporter of cell wall stress, in the model gram-positive bacterium Bacillus subtilis.

T L Czarny, A L Perri, S French, E D Brown

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

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

19 citing papers in PubMed.

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  6. Inhibition ofMicrobiology (Reading, England) · 2022
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  18. The Canadian Institutes of Health Research response to antimicrobial resistance.Canada communicable disease report = Releve des maladies transmissibles au Canada · 2015
    Article
  19. 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

4 authors.

T L CzarnyDepartment of Biochemistry and Biomedical Sciences and Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
A L PerriDepartment of Biochemistry and Biomedical Sciences and Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
S FrenchDepartment of Biochemistry and Biomedical Sciences and Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
E D BrownDepartment of Biochemistry and Biomedical Sciences and Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada ebrown@mcmaster.ca.

Funding

Canadian Institutes of Health Research MOP-15496
6 · The paper itself

Abstract

The emergence of antibiotic resistance in recent years has radically reduced the clinical efficacy of many antibacterial treatments and now poses a significant threat to public health. One of the earliest studied well-validated targets for antimicrobial discovery is the bacterial cell wall. The essential nature of this pathway, its conservation among bacterial pathogens, and its absence in human biology have made cell wall synthesis an attractive pathway for new antibiotic drug discovery. Herein, we describe a highly sensitive screening methodology for identifying chemical agents that perturb cell wall synthesis, using the model of the Gram-positive bacterium Bacillus subtilis. We report on a cell-based pilot screen of 26,000 small molecules to look for cell wall-active chemicals in real time using an autonomous luminescence gene cluster driven by the promoter of ywaC, which encodes a guanosine tetra(penta)phosphate synthetase that is expressed under cell wall stress. The promoter-reporter system was generally much more sensitive than growth inhibition testing and responded almost exclusively to cell wall-active antibiotics. Follow-up testing of the compounds from the pilot screen with secondary assays to verify the mechanism of action led to the discovery of 9 novel cell wall-active compounds.

Indexed as

Anti-Bacterial AgentsBacillus subtilisCell MembraneCell WallDose-Response Relationship, DrugGenes, BacterialGenes, ReporterHigh-Throughput Screening AssaysLigasesMicrobial Sensitivity TestsPermeabilitySmall Molecule LibrariesTranscription, GeneticAnti-Bacterial Agentsguanosine pentaphosphate synthetaseLigasesSmall Molecule Libraries

Identifiers

PMID24687489
PMCPMC4068450

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.