Evidence map›Paper›PMID 25331704›Full record

ArticleAntimicrobial agents and chemotherapy2015

Identification of inhibitors of a bacterial sigma factor using a new high-throughput screening assay.

S A El-Mowafi, E Sineva, J N Alumasa, H Nicoloff, J W Tomsho, S E Ades, K C Keiler

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

10 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. A high-throughput system to identify inhibitors ofProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  9. Article
  10. 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

7 authors at 1 institution in 1 country.

S A El-MowafiDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
E SinevaDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.ORCID http://orcid.org/0000-0003-2307-0581
J N AlumasaDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
H NicoloffDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
J W TomshoDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
S E AdesDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.
K C KeilerDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA kkeiler@psu.edu.
Pennsylvania State University · US

Funding

The Role of tmRNA in development of C. crescentusR01GM068720 · NIGMS · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI KEILER, KENNETH C · 2004 to 2014
$2.3M
Integrating Cell Envelope and Starvation Stress: Regulation of Sigma(E) by ppGppR01GM097365 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI ADES, SARAH E · 2012 to 2016
$1.3M
Assay Development for Inhibitors of the Essential sRNA-Sigma E Virulence FactorsR21NS071542 · NINDS · PENNSYLVANIA STATE UNIVERSITY, THE · PI ADES, SARAH E · 2010 to 2010
$148k
NIGMS NIH HHS GM68720NIGMS NIH HHS R01 GM068720NIGMS NIH HHS R01 GM097365NINDS NIH HHS NS071542NINDS NIH HHS R21 NS071542
6 · The paper itself

Abstract

Gram-negative bacteria are formidable pathogens because their cell envelope presents an adaptable barrier to environmental and host-mediated challenges. The stress response pathway controlled by the alternative sigma factor σ(E) is critical for maintenance of the cell envelope. Because σ(E) is required for the virulence or viability of several Gram-negative pathogens, it might be a useful target for antibiotic development. To determine if small molecules can inhibit the σ(E) pathway, and to permit high-throughput screening for antibiotic lead compounds, a σ(E) activity assay that is compatible with high-throughput screening was developed and validated. The screen employs a biological assay with positive readout. An Escherichia coli strain was engineered to express yellow fluorescent protein (YFP) under negative regulation by the σ(E) pathway, such that inhibitors of the pathway increase the production of YFP. To validate the screen, the reporter strain was used to identify σ(E) pathway inhibitors from a library of cyclic peptides. Biochemical characterization of one of the inhibitory cyclic peptides showed that it binds σ(E), inhibits RNA polymerase holoenzyme formation, and inhibits σ(E)-dependent transcription in vitro. These results demonstrate that alternative sigma factors can be inhibited by small molecules and enable high-throughput screening for inhibitors of the σ(E) pathway.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsEscherichia coliGene Expression Regulation, BacterialHigh-Throughput Screening AssaysInteinsLuminescent ProteinsLysineMetabolic Networks and PathwaysPeptides, CyclicProtein SplicingReproducibility of ResultsSigma FactorSmall Molecule LibrariesAnti-Bacterial AgentsBacterial ProteinsLuminescent ProteinsLysinePeptides, CyclicSigma FactorSmall Molecule Librariesyellow fluorescent protein, Bacteria

Identifiers

PMID25331704
PMCPMC4291351
OpenAlexW2035812257

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.