Evidence map›Paper›PMID 25385118›Full record

ArticleAntimicrobial agents and chemotherapy2015

Testing tuberculosis drug efficacy in a zebrafish high-throughput translational medicine screen.

Anita Ordas, Robert-Jan Raterink, Fraser Cunningham, Hans J Jansen, Malgorzata I Wiweger, Susanne Jong-Raadsen, Sabine Bos, Robert H Bates, David Barros, Annemarie H Meijer and 5 more

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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

28 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Identification of a Drug Candidate againstJournal of microbiology and biotechnology · 2025
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Thiostrepton: A Novel Therapeutic Drug Candidate forMolecules (Basel, Switzerland) · 2019
    Article
  14. Article
  15. Article
  16. Article
  17. Nano-Sampling and Reporter Tools to Study Metabolic Regulation in Zebrafish.Frontiers in cell and developmental biology · 2019
    Article
  18. Frontiers in microbiology · 2019
    Article
  19. The Zebrafish as a Model Host for Invasive Fungal Infections.Journal of fungi (Basel, Switzerland) · 2018
    Review
  20. 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

15 authors at 3 institutions in 2 countries.

Anita OrdasIBL, Leiden University, Leiden, The Netherlands.
Robert-Jan RaterinkDivision of Analytical BioSciences, Leiden Academic Centre for Drug Research and Netherlands Metabolomics Centre, Leiden University, Leiden, The Netherlands.
Fraser CunninghamGlaxoSmithKline, Tres Cantos, Spain.
Hans J JansenZF-screens B.V., Leiden, The Netherlands.
Malgorzata I WiwegerIBL, Leiden University, Leiden, The Netherlands ZF-screens B.V., Leiden, The Netherlands.
Susanne Jong-RaadsenZF-screens B.V., Leiden, The Netherlands.
Sabine BosDivision of Analytical BioSciences, Leiden Academic Centre for Drug Research and Netherlands Metabolomics Centre, Leiden University, Leiden, The Netherlands.
Robert H BatesGlaxoSmithKline, Tres Cantos, Spain.
David BarrosGlaxoSmithKline, Tres Cantos, Spain.
Annemarie H MeijerIBL, Leiden University, Leiden, The Netherlands.
Rob J VreekenDivision of Analytical BioSciences, Leiden Academic Centre for Drug Research and Netherlands Metabolomics Centre, Leiden University, Leiden, The Netherlands.
Lluís Ballell-PagesGlaxoSmithKline, Tres Cantos, Spain.
Ron P DirksZF-screens B.V., Leiden, The Netherlands.
Thomas HankemeierDivision of Analytical BioSciences, Leiden Academic Centre for Drug Research and Netherlands Metabolomics Centre, Leiden University, Leiden, The Netherlands hankemeier@lacdr.leidenuniv.nl h.p.spaink@biology.leidenuniv.nl.
Herman P SpainkIBL, Leiden University, Leiden, The Netherlands hankemeier@lacdr.leidenuniv.nl h.p.spaink@biology.leidenuniv.nl.
Leiden University · NLGlaxoSmithKline (Spain) · ESZF Screens (Netherlands) · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The translational value of zebrafish high-throughput screens can be improved when more knowledge is available on uptake characteristics of potential drugs. We investigated reference antibiotics and 15 preclinical compounds in a translational zebrafish-rodent screening system for tuberculosis. As a major advance, we have developed a new tool for testing drug uptake in the zebrafish model. This is important, because despite the many applications of assessing drug efficacy in zebrafish research, the current methods for measuring uptake using mass spectrometry do not take into account the possible adherence of drugs to the larval surface. Our approach combines nanoliter sampling from the yolk using a microneedle, followed by mass spectrometric analysis. To date, no single physicochemical property has been identified to accurately predict compound uptake; our method offers a great possibility to monitor how any novel compound behaves within the system. We have correlated the uptake data with high-throughput drug-screening data from Mycobacterium marinum-infected zebrafish larvae. As a result, we present an improved zebrafish larva drug-screening platform which offers new insights into drug efficacy and identifies potential false negatives and drugs that are effective in zebrafish and rodents. We demonstrate that this improved zebrafish drug-screening platform can complement conventional models of in vivo Mycobacterium tuberculosis-infected rodent assays. The detailed comparison of two vertebrate systems, fish and rodent, may give more predictive value for efficacy of drugs in humans.

Indexed as

AnimalsAntitubercular AgentsDrug Evaluation, PreclinicalLarvaTranslational Research, BiomedicalTuberculosisAntitubercular Agents

Identifiers

PMID25385118
PMCPMC4335901
OpenAlexW2141023795

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.