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dc.contributor.authorBalzano, Phillip Mario Jan
dc.contributor.authorCunningham, Aimee L.
dc.contributor.authorGrassel, Christen
dc.contributor.authorBarry, Eileen M.
dc.date.accessioned2018-03-19T17:53:12Z
dc.date.available2018-03-19T17:53:12Z
dc.date.issued2018-01
dc.identifier.citationBalzano PM, Cunningham AL, Grassel C, Barry EM. (2018). Deletion of the Major Facilitator Superfamily Transporter fptB Alters Host Cell Interactions and Attenuates Virulence of Type A Francisella tularensis. Infection and Immunity, 86:e00832-17, DOI: 10.1128/IAI.00832-17en_US
dc.identifier.urihttp://hdl.handle.net/10713/7556
dc.description.abstractFrancisella tularensis is a Gram negative facultative intracellular coccobacillus that can infect a wide variety of hosts. In humans, F. tularensis causes the zoonosis tularemia following insect bites, ingestion, inhalation, and the handling of infected animals. That a very small inoculum delivered by the aerosol route can cause severe disease, coupled with the possibility of its use as an aerosolized bioweapon, have led to the classification of Francisella tularensis as a Category A select agent and has renewed interest in the formulation of a vaccine. To this end, we engineered a Type A strain SchuS4 derivative containing a targeted deletion of major facilitator superfamily (MFS) transporter fptB. Based on the attenuating capacity of this deletion in the F. tularensis LVS background, we hypothesized that deletion of this transporter would alter intracellular replication and cytokine induction of the Type A strain and attenuate virulence in the stringent C57BL/6J mouse model. Here we demonstrate that deletion of fptB significantly alters the intracellular lifecycle of F. tularensis, attenuating intracellular replication in both cell line and primary macrophages, and inducing a novel cytosolic escape delay. Additionally, we observed prominent differences in the in vitro cytokine profile in human macrophage-like cells. The mutant was highly attenuated in the C57BL/6J mouse model, and provided partial protection against virulent Type A F. tularensis challenge. These results indicate a fundamental necessity for this nutrient transporter in the timely progression of F. tularensis through its replication cycle, and in pathogenesis.en_US
dc.language.isoen_USen_US
dc.publisherWashington DC: The American Society for Microbiologyen_US
dc.subjectmajor facilitator superfamily transporteren_US
dc.subjectMFS transporteren_US
dc.subject.meshFrancisella tularensis--pathogenicityen_US
dc.subject.meshTularemia--prevention & controlen_US
dc.subject.meshVaccinesen_US
dc.titleDeletion of the MFS transporter fptB alters host cell interactions and attenuates the virulence of Type A Francisella tularensisen_US
dc.title.alternativeDeletion of the Major Facilitator Superfamily Transporter fptB Alters Host Cell Interactions and Attenuates Virulence of Type A Francisella tularensisen_US
dc.typeManuscripten_US
dc.description.urinameFull Texten_US
refterms.dateFOA2019-02-19T18:13:17Z


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