Evidence map›Paper›PMID 23571538›Full record

ArticleAntimicrobial agents and chemotherapy2013

Comparison of a high-throughput high-content intracellular Leishmania donovani assay with an axenic amastigote assay.

Manu De Rycker, Irene Hallyburton, John Thomas, Lorna Campbell, Susan Wyllie, Dhananjay Joshi, Scott Cameron, Ian H Gilbert, Paul G Wyatt, Julie A Frearson and 2 more

Erratum issuedAbstract readComparative Study
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
–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

81 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Can floral nectars reduce transmission of Leishmania?PLoS neglected tropical diseases · 2022
    Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Current leishmaniasis drug discovery.RSC medicinal chemistry · 2022
    Review
  14. Article
  15. Synthesis and Anti-Molecules (Basel, Switzerland) · 2022
    Article
  16. Article
  17. Article
  18. Challenges and Tools for In VitroPathogens (Basel, Switzerland) · 2021
    Review
  19. Review
  20. Article

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

12 authors.

Manu De RyckerDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, United Kingdom. m.derycker@dundee.ac.uk
Irene Hallyburton
John Thomas
Lorna Campbell
Susan Wyllie
Dhananjay Joshi
Scott Cameron
Ian H Gilbert
Paul G Wyatt
Julie A Frearson
Alan H Fairlamb
David W Gray

Funding

Wellcome TrustWellcome Trust 079838Wellcome Trust 083481
6 · The paper itself

Abstract

Visceral leishmaniasis is a neglected tropical disease with significant health impact. The current treatments are poor, and there is an urgent need to develop new drugs. Primary screening assays used for drug discovery campaigns have typically used free-living forms of the Leishmania parasite to allow for high-throughput screening. Such screens do not necessarily reflect the physiological situation, as the disease-causing stage of the parasite resides inside human host cells. Assessing the drug sensitivity of intracellular parasites on scale has recently become feasible with the advent of high-content screening methods. We describe here a 384-well microscopy-based intramacrophage Leishmania donovani assay and compare it to an axenic amastigote system. A panel of eight reference compounds was tested in both systems, as well as a human counterscreen cell line, and our findings show that for most clinically used compounds both axenic and intramacrophage assays report very similar results. A set of 15,659 diverse compounds was also screened using both systems. This resulted in the identification of seven new antileishmanial compounds and revealed a high false-positive rate for the axenic assay. We conclude that the intramacrophage assay is more suited as a primary hit-discovery platform than the current form of axenic assay, and we discuss how modifications to the axenic assay may render it more suitable for hit-discovery.

Indexed as

Parasitic Sensitivity TestsAntiprotozoal AgentsAxenic CultureCell LineDrug DiscoveryHigh-Throughput Screening AssaysHumansLeishmania donovaniLeishmaniasis, VisceralMacrophagesAntiprotozoal Agents

Identifiers

PMID23571538
PMCPMC3697379

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.