The Ability to Acquire Iron Is Inversely Related to Virulence and the Protective Efficacy of Francisella tularensis Live Vaccine Strain

Joshua R Fletcher; Deborah D Crane; Tara D Wehrly; Craig A Martens; Catharine M Bosio; Bradley D Jones

doi:10.3389/fmicb.2018.00607

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The Ability to Acquire Iron Is Inversely Related to Virulence and the Protective Efficacy of Francisella tularensis Live Vaccine Strain

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The Ability to Acquire Iron Is Inversely Related to Virulence and the Protective Efficacy of Francisella tularensis Live Vaccine Strain

Joshua R Fletcher, Deborah D Crane, Tara D Wehrly, Craig A Martens, Catharine M Bosio and Bradley D Jones

Frontiers in microbiology, Vol.9, pp.607-607

04/04/2018

DOI: 10.3389/fmicb.2018.00607

PMCID: PMC5893802

PMID: 29670588

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Abstract

Francisella tularensis is a highly infectious bacterial pathogen that causes the potentially fatal disease tularemia. The Live Vaccine Strain (LVS) of F. tularensis subsp. holarctica , while no longer licensed as a vaccine, is used as a model organism for identifying correlates of immunity and bacterial factors that mediate a productive immune response against F. tularensis . Recently, it was reported that two biovars of LVS differed in their virulence and vaccine efficacy. Genetic analysis showed that they differ in ferrous iron homeostasis; lower Fe 2+ levels contributed to increased resistance to hydrogen peroxide in the vaccine efficacious LVS biovar. This also correlated with resistance to the bactericidal activity of interferon γ-stimulated murine bone marrow-derived macrophages. We have extended these findings further by showing that a mutant lacking bacterioferritin stimulates poor protection against Schu S4 challenge in a mouse model of tularemia. Together these results suggest that the efficacious biovar of LVS stimulates productive immunity by a mechanism that is dependent on its ability to limit the toxic effects of oxidative stress by maintaining optimally low levels of intracellular Fe 2+ .

inflammatory mechanisms

virulence mechanisms

Microbiology

intracellular pathogen

microbial pathogenesis

iron acquisition mechanism

Francisella tularensis

Details

Title: Subtitle: The Ability to Acquire Iron Is Inversely Related to Virulence and the Protective Efficacy of Francisella tularensis Live Vaccine Strain
Creators: Joshua R Fletcher - Graduate Program in Genetics, University of Iowa
Deborah D Crane - Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites
Tara D Wehrly - Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites
Craig A Martens - Genomics Core, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health
Catharine M Bosio - Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites
Bradley D Jones - Graduate Program in Genetics, University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in microbiology, Vol.9, pp.607-607
DOI: 10.3389/fmicb.2018.00607
PMID: 29670588
PMCID: PMC5893802
NLM abbreviation: Front Microbiol
ISSN: 1664-302X
eISSN: 1664-302X
Publisher: Frontiers Media S.A
Grant note: 2PO1 AI044642; 2U54 AI057160 / National Institutes of Health
Language: English
Date published: 04/04/2018
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083269902771

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