Evidence map›Paper›PMID 33186989›Full record

ArticleFEMS microbiology letters2020

High-density transposon libraries utilising outward-oriented promoters identify mechanisms of action and resistance to antimicrobials.

Chris Coward, Gopujara Dharmalingham, Omar Abdulle, Tim Avis, Stephan Beisken, Elena Breidenstein, Natasha Carli, Luis Figueiredo, David Jones, Nawaz Khan and 8 more

Open access · hybridAbstract read
In one paragraph

Article in FEMS microbiology letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Inactivation ofMicrobiology spectrum · 2023
    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

18 authors at 2 institutions in 1 country.

Chris CowardSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Gopujara DharmalinghamSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Omar AbdulleSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Tim AvisSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Stephan BeiskenSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Elena BreidensteinSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Natasha CarliSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Luis FigueiredoSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
David JonesSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Nawaz KhanSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Sara MalaraSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Joana MartinsSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Nabeetha NagalingamSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Keith TurnerQuadram Institute, Rosalind Franklin Road, Norwich Research Park, Norwich, NR4 7UQ, UK.
John WainQuadram Institute, Rosalind Franklin Road, Norwich Research Park, Norwich, NR4 7UQ, UK.
David WilliamsNanna Therapeutics, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
David PowellSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Clive MasonSummit Therapeutics plc, The Merrifield Centre, 12 Rosemary Lane, Cambridge, CB1 3LQ, UK.
Summit (United Kingdom) · GBNorwich Research Park · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The use of bacterial transposon mutant libraries in phenotypic screens is a well-established technique for determining which genes are essential or advantageous for growth in conditions of interest. Standard, inactivating, transposon libraries cannot give direct information about genes whose over-expression gives a selective advantage. We report the development of a system wherein outward-oriented promoters are included in mini-transposons, generation of transposon mutant libraries in Escherichia coli and Pseudomonas aeruginosa and their use to probe genes important for growth under selection with the antimicrobial fosfomycin, and a recently-developed leucyl-tRNA synthase inhibitor. In addition to the identification of known mechanisms of action and resistance, we identify the carbon-phosphorous lyase complex as a potential resistance liability for fosfomycin in E. coli and P. aeruginosa. The use of this technology can facilitate the development of novel mechanism-of-action antimicrobials that are urgently required to combat the increasing threat worldwide from antimicrobial-resistant pathogenic bacteria.

Indexed as

Anti-Bacterial AgentsDNA Transposable ElementsDrug Resistance, BacterialEscherichia coliGene LibraryPromoter Regions, GeneticPseudomonas aeruginosaAnti-Bacterial AgentsDNA Transposable Elementsantibioticbacteriadevelopmentmechanismmutagenesisresistance

Identifiers

PMID33186989
PMCPMC7735965
OpenAlexW3105778796

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.