Evidence map›Paper›PMID 14715274›Full record

ArticleBiochemical and biophysical research communications2004

A two-component signal transduction system with a PAS domain-containing sensor is required for virulence of Mycobacterium tuberculosis in mice.

Lisa Rickman, José W Saldanha, Debbie M Hunt, Dominic N Hoar, M Joseph Colston, Jonathan B A Millar, Roger S Buxton

Open access · greenAbstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

34 citing papers in PubMed, 74 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

Lisa RickmanDivision of Mycobacterial Research, National Institute for Medical Research, London, UK. lr2@sanger.ac.uk
José W Saldanha
Debbie M Hunt
Dominic N Hoar
M Joseph Colston
Jonathan B A Millar
Roger S Buxton
National Institute for Health Research · GB

Funding

Medical Research Council MC_U117531948Medical Research Council MC_U117585867Medical Research Council U.1175.02.002.00013 (85867)Wellcome Trust
6 · The paper itself

Abstract

Mycobacterium tuberculosis, the causative organism of tuberculosis, encounters oxidative stress during phagocytosis by the macrophage and following macrophage activation during an acquired immune response, and also from internally generated sources of radical oxygen intermediates through intermediary metabolism. We have identified the SenX3 protein, a sensor in 1 of the 11 complete pairs of two-component signal transduction systems in M. tuberculosis, as a possible orthologue of the Mak2p protein from the fission yeast Schizosaccharomyces pombe that is known to sense peroxide stress. Moreover, the SenX3-RegX3 two-component system was the top scoring hit in a homology search with the Escherichia coli ArcB-ArcA global control system of aerobic genes. Using structural modelling techniques we have determined that SenX3 contains a PAS-like domain found in a variety of prokaryotic and eukaryotic sensors of oxygen and redox. Mutants with knock-outs of senX3 or of the accompanying transcriptional regulator regX3 were constructed and found to have reduced virulence in a mouse model of tuberculosis infection, the mutant bacteria persisting for up to 4 months post-infection; complemented mutants had regained virulence confirming that it was mutations of this two-component system that were responsible for the avirulent phenotype. This work identifies the PAS domain as a possible drug target for tuberculosis and mutations in the senX3-regX signal transduction system as potentially useful components of live vaccine strains.

Indexed as

Models, MolecularAmino Acid SequenceAnimalsBacterial ProteinsComputer SimulationFemaleMiceMice, Inbred BALB CMolecular Sequence DataMutationMycobacterium tuberculosisOxidative StressPhosphotransferasesProtein Structure, TertiaryRecombinant ProteinsSequence AlignmentBacterial ProteinsPhosphotransferasesRecombinant ProteinsSenX3 protein, Mycobacterium

Identifiers

PMID14715274
PMCPMC2963928
OpenAlexW2119387381

What OpenQuestion holds

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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.