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dc.contributor.authorHobbs, Brandi E
dc.contributor.authorMatson, Courtney A
dc.contributor.authorTheofilou, Vasileios I
dc.contributor.authorWebb, Tonya J
dc.contributor.authorYounis, Rania H
dc.contributor.authorBarry, Eileen M
dc.date.accessioned2021-07-16T13:18:54Z
dc.date.available2021-07-16T13:18:54Z
dc.date.issued2021-06-24
dc.identifier.urihttp://hdl.handle.net/10713/16199
dc.description.abstractFrancisella tularensis (Ft) is a Gram-negative, facultative intracellular bacterium that is a Tier 1 Select Agent of concern for biodefense for which there is no licensed vaccine. A subfamily of 9 Francisella phagosomal transporter (fpt) genes belonging to the Major Facilitator Superfamily of transporters was identified as critical to pathogenesis and potential targets for attenuation and vaccine development. We evaluated the attenuation and protective capacity of LVS derivatives with deletions of the fptA and fptF genes in the C57BL/6J mouse model of respiratory tularemia. LVSΔfptA and LVSΔfptF were highly attenuated with LD50 values of >20 times that of LVS when administered intranasally and conferred 100% protection against lethal challenge. Immune responses to the fpt mutant strains in mouse lungs on day 6 post-infection were substantially modified compared to LVS and were associated with reduced organ burdens and reduced pathology. The immune responses to LVSΔfptA and LVSΔfptF were characterized by decreased levels of IL-10 and IL-1β in the BALF versus LVS, and increased numbers of B cells, αβ and γδ T cells, NK cells, and DCs versus LVS. These results support a fundamental requirement for FptA and FptF in the pathogenesis of Ft and the modulation of the host immune response.en_US
dc.description.urihttps://doi.org/10.3390/pathogens10070799en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofPathogens (Basel, Switzerland)en_US
dc.subjectC57BL/6J miceen_US
dc.subjectFrancisella tularensisen_US
dc.subjectLive Vaccine Strain (LVS)en_US
dc.subjectMFS transporteren_US
dc.subjectattenuationen_US
dc.subjectcytokinesen_US
dc.subjectflow cytometryen_US
dc.subjecthistopathologyen_US
dc.subjectlive attenuated vaccineen_US
dc.subjectorgan burdensen_US
dc.titleDeletion Mutants of Phagosomal Transporters FptA and FptF Are Highly Attenuated for Virulence and Are Protective Against Lethal Intranasal LVS Challenge in a Murine Model of Respiratory Tularemiaen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/pathogens10070799
dc.identifier.pmid34202420
dc.source.volume10
dc.source.issue7
dc.source.countryUnited States
dc.source.countrySwitzerland


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