Evidence map›Paper›PMID 17220416›Full record

ArticleAntimicrobial agents and chemotherapy2007

EthA, a common activator of thiocarbamide-containing drugs acting on different mycobacterial targets.

Lynn G Dover, Anuradha Alahari, Paul Gratraud, Jessica M Gomes, Veemal Bhowruth, Robert C Reynolds, Gurdyal S Besra, Laurent Kremer

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 160 citations in OpenAlex.

  1. Review
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  14. Hit Compounds and Associated Targets in IntracellularMolecules (Basel, Switzerland) · 2022
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  15. Experimental Confirmation that an UncommonAntimicrobial agents and chemotherapy · 2022
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6 more citing papers are in PubMed but not listed here.

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 5 institutions in 3 countries.

Lynn G DoverSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Anuradha Alahari
Paul Gratraud
Jessica M Gomes
Veemal Bhowruth
Robert C Reynolds
Gurdyal S Besra
Laurent Kremer
University of Birmingham · GBCentre National de la Recherche Scientifique · FRLaboratory of Pathogens and Host Immunity · FRSouthern Research Institute · USUniversité de Montpellier · FR

Funding

Medical Research Council G0400789Wellcome Trust
6 · The paper itself

Abstract

Many of the current antimycobacterial agents require some form of cellular activation unmasking reactive groups, which in turn will bind to their specific targets. Therefore, understanding the mechanisms of activation of current antimycobacterials not only helps to decipher mechanisms of drug resistance but may also facilitate the development of alternative activation strategies or of analogues that do not require such processes. Herein, through the use of genetically defined strains of Mycobacterium bovis BCG we provide evidence that EthA, previously shown to activate ethionamide, also converts isoxyl (ISO) and thiacetazone (TAC) into reactive species. These results were further supported by the development of an in vitro assay using purified recombinant EthA, which allowed direct assessment of the metabolism of ISO. Interestingly, biochemical analysis of [(14)C]acetate-labeled cultures suggested that all of these EthA-activated drugs inhibit mycolic acid biosynthesis via different mechanisms through binding to specific targets. This report is also the first description of the molecular mechanism of action of TAC, a thiosemicarbazone antimicrobial agent that is still used in the treatment of tuberculosis as a second-line drug in many developing countries. Altogether, the results suggest that EthA is a common activator of thiocarbamide-containing drugs. The broad specificity of EthA can now be used to improve the activation process of these drugs, which may help overcome the toxicity problems associated with clinical thiocarbamide use.

Indexed as

Antitubercular AgentsBacterial ProteinsCloning, MolecularDNA, BacterialElectrophoresis, Polyacrylamide GelFatty AcidsMicrobial Sensitivity TestsMycobacteriumMycobacterium bovisMycolic AcidsOxygenasesPlasmidsProdrugsThioacetazoneAntitubercular AgentsBacterial ProteinsDNA, BacterialetaA protein, Mycobacterium tuberculosisFatty AcidsMycolic AcidsOxygenasesProdrugsThioacetazone

Identifiers

PMID17220416
PMCPMC1803108
OpenAlexW2015771874

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.