Evidence map›Paper›PMID 20385757›Full record

ArticleInfection and immunity2010

Francisella tularensis DeltapyrF mutants show that replication in nonmacrophages is sufficient for pathogenesis in vivo.

Joseph Horzempa, Dawn M O'Dee, Robert M Q Shanks, Gerard J Nau

Abstract read
In one paragraph

Article in Infection and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

41 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Review
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  9. The Role and Mechanism of Erythrocyte Invasion byFrontiers in cellular and infection microbiology · 2017
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  10. The orange spotted cockroach (Proceedings of the West Virginia Academy of Science · 2017
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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

4 authors at 2 institutions in 2 countries.

Joseph HorzempaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Dawn M O'Dee
Robert M Q Shanks
Gerard J Nau
Office of Infectious Diseases · USUniversity of Pittsburgh · US

Funding

Immunology of Infectious DiseaseT32AI060525 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JoAnne L. Flynn · 2005 to 2026
$5.3M
Novel Selectable Markers for F. tularensisR21AI074402 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NAU, GERARD J · 2007 to 2008
$393k
NIAID NIH HHS AI050018NIAID NIH HHS AI074402NIAID NIH HHS N01 AI050018NIAID NIH HHS R21 AI074402NIAID NIH HHS T32 AI060525
6 · The paper itself

Abstract

The pathogenesis of Francisella tularensis has been associated with this bacterium's ability to replicate within macrophages. F. tularensis can also invade and replicate in a variety of nonphagocytic host cells, including lung and kidney epithelial cells and hepatocytes. As uracil biosynthesis is a central metabolic pathway usually necessary for pathogens, we characterized DeltapyrF mutants of both F. tularensis LVS and Schu S4 to investigate the role of these mutants in intracellular growth. As expected, these mutant strains were deficient in de novo pyrimidine biosynthesis and were resistant to 5-fluoroorotic acid, which is converted to a toxic product by functional PyrF. The F. tularensis DeltapyrF mutants could not replicate in primary human macrophages. The inability to replicate in macrophages suggested that the F. tularensis DeltapyrF strains would be attenuated in animal infection models. Surprisingly, these mutants retained virulence during infection of chicken embryos and in the murine model of pneumonic tularemia. We hypothesized that the F. tularensis DeltapyrF strains may replicate in cells other than macrophages to account for their virulence. In support of this, F. tularensis DeltapyrF mutants replicated in HEK-293 cells and normal human fibroblasts in vitro. Moreover, immunofluorescence microscopy showed abundant staining of wild-type and mutant bacteria in nonmacrophage cells in the lungs of infected mice. These findings indicate that replication in nonmacrophages contributes to the pathogenesis of F. tularensis.

Indexed as

Gene DeletionAnimalsBacterial ProteinsCell LineCells, CulturedChick EmbryoChickensDisease Models, AnimalEpithelial CellsFemaleFibroblastsFrancisella tularensisHumansLungMacrophagesMiceBacterial ProteinsVirulence Factors

Identifiers

PMID20385757
PMCPMC2876533
OpenAlexW2169393979

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.