Evidence map›Paper›PMID 24374051›Full record

ArticleMicrobes and infection2014

The contribution of the glycine cleavage system to the pathogenesis of Francisella tularensis.

Matthew J Brown, Brian C Russo, Dawn M O'Dee, Deanna M Schmitt, Gerard J Nau

Open access · greenAbstract read
In one paragraph

Article in Microbes and infection, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

18 citing papers in PubMed, 23 citations in OpenAlex.

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  13. Jejunal Metabolic Responses toFrontiers in microbiology · 2018
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  15. Importance of Metabolic Adaptations inFrontiers in cellular and infection microbiology · 2017
    Review
  16. Differential Substrate Usage and Metabolic Fluxes inFrontiers in cellular and infection microbiology · 2017
    Article
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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

5 authors at 1 institution in 1 country.

Matthew J BrownDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Brian C RussoDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Dawn M O'DeeDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Deanna M SchmittDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Gerard J NauDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Medicine - Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: gjnau@pitt.edu.
University of Pittsburgh · US

Funding

Viral Persistence and PathogenesisT32AI049820 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELUCA, NEAL A. · 2001 to 2024
$5.5M
Immunology of Infectious DiseaseT32AI060525 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JoAnne L. Flynn · 2005 to 2026
$5.3M
NIAID NIH HHS T32 AI049820NIAID NIH HHS T32 AI060525
6 · The paper itself

Abstract

Biosynthesis and acquisition of nutrients during infection are integral to pathogenesis. Members of a metabolic pathway, the glycine cleavage system, have been identified in virulence screens of the intracellular bacterium Francisella tularensis but their role in pathogenesis remains unknown. This system generates 5,10-methylenetetrahydrofolate, a precursor of amino acid and DNA synthesis, from glycine degradation. To characterize this pathway, deletion of the gcvT homolog, an essential member of this system, was performed in attenuated and virulent F. tularensis strains. Deletion mutants were auxotrophic for serine but behaved similar to wild-type strains with respect to host cell invasion, intracellular replication, and stimulation of TNF-α. Unexpectedly, the glycine cleavage system was required for the pathogenesis of virulent F. tularensis in a murine model. Deletion of the gcvT homolog delayed mortality and lowered bacterial burden, particularly in the liver and bloodstream. To reconcile differences between the cell culture model and animal model, minimal tissue culture media was employed to mimic the nutritionally limiting environment of the host. This reevaluation demonstrated that the glycine cleavage system contributes to the intracellular replication of virulent F. tularensis in serine limiting environments. Thus, the glycine cleavage system is the serine biosynthetic pathway of F. tularensis and contributes to pathogenesis in vivo.

Indexed as

Amino Acid OxidoreductasesCarrier ProteinsMultienzyme ComplexesTransferasesAnimalsBacterial ProteinsDisease Models, AnimalFrancisella tularensisGene DeletionMice, Inbred C57BLTetrahydrofolatesTularemiaVirulence5,10-methylenetetrahydrofolic acidAmino Acid OxidoreductasesBacterial ProteinsCarrier Proteinsglycine cleavage systemMultienzyme ComplexesTetrahydrofolatesTransferasesBacterial infectionsFrancisella tularensisGlycine cleavage systemHost–pathogen interactionsMetabolismPathogenicity

Identifiers

PMID24374051
PMCPMC4089098
OpenAlexW2091926049

What OpenQuestion holds

Textmetadata
LicenceTDM
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.