Evidence map›Paper›PMID 23633686›Full record

ArticleThe Journal of antimicrobial chemotherapy2013

Rapid in vivo assessment of drug efficacy against Mycobacterium tuberculosis using an improved firefly luciferase.

Nuria Andreu, Andrea Zelmer, Samantha L Sampson, Melanie Ikeh, Gregory J Bancroft, Ulrich E Schaible, Siouxsie Wiles, Brian D Robertson

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Review
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  8. Review
  9. Article
  10. Antimicrobial agents and chemotherapy · 2021
    Article
  11. Isolation of a Novel Polyketide fromMolecules (Basel, Switzerland) · 2021
    Article
  12. Article
  13. Imaging of bioluminescentThe Journal of international medical research · 2020
    Article
  14. In Vivo Imaging of BioluminescentThe American journal of tropical medicine and hygiene · 2019
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

8 authors at 4 institutions in 3 countries.

Nuria AndreuMRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, UK.
Andrea Zelmer
Samantha L Sampson
Melanie Ikeh
Gregory J Bancroft
Ulrich E Schaible
Siouxsie Wiles
Brian D Robertson
Imperial College London · GBLondon School of Hygiene & Tropical Medicine · GBResearch Center Borstel - Leibniz Lung Center · DEUniversity of Auckland · NZ

Funding

Medical Research Council MR/J006874/1
6 · The paper itself

Abstract

objectivesIn vivo experimentation is costly and time-consuming, and presents a major bottleneck in anti-tuberculosis drug development. Conventional methods rely on the enumeration of bacterial colonies, and it can take up to 4 weeks for Mycobacterium tuberculosis to grow on agar plates. Light produced by recombinant bacteria expressing luciferase enzymes can be used as a marker of bacterial load, and disease progression can be easily followed non-invasively in live animals by using the appropriate imaging equipment. The objective of this work was to develop a bioluminescence-based mouse model of tuberculosis to assess antibiotic efficacy against M. tuberculosis in vivo.

methodsWe used an M. tuberculosis strain carrying a red-shifted derivative of the firefly luciferase gene (FFlucRT) to infect mice, and monitored disease progression in living animals by bioluminescence imaging before and after treatment with the frontline anti-tuberculosis drug isoniazid. The resulting images were analysed and the bioluminescence was correlated with bacterial counts.

resultsUsing bioluminescence imaging we detected as few as 1.7 × 10(3) and 7.5 × 10(4) reporter bacteria ex vivo and in vivo, respectively, in the lungs of mice. A good correlation was found between bioluminescence and bacterial load in both cases. Furthermore, a marked reduction in luminescence was observed in living mice given isoniazid treatment.

conclusionsWe have shown that an improved bioluminescent strain of M. tuberculosis can be visualized by non-invasive imaging in live mice during an acute, progressive infection and that this technique can be used to rapidly visualize and quantify the effect of antibiotic treatment. We believe that the model presented here will be of great benefit in early drug discovery as an easy and rapid way to identify active compounds in vivo.

Indexed as

AnimalsAntitubercular AgentsDisease Models, AnimalDrug Evaluation, PreclinicalFemaleGenes, ReporterLuciferases, FireflyLuminescent MeasurementsMiceMolecular Sequence DataMycobacterium tuberculosisSequence Analysis, DNATuberculosisWhole Body ImagingAntitubercular AgentsLuciferases, Fireflybioluminescencedrug testingmouse modeloptical imaging

Identifiers

PMID23633686
PMCPMC3743513
OpenAlexW2147139627

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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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.