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dc.contributor.authorLovchik, Julie A
dc.contributor.authorReed, Douglas S
dc.contributor.authorHutt, Julie A
dc.contributor.authorXia, Fangfang
dc.contributor.authorStevens, Rick L
dc.contributor.authorModise, Thero
dc.contributor.authorBarry, Eileen M
dc.contributor.authorWu, Terry H
dc.date.accessioned2021-06-09T13:20:59Z
dc.date.available2021-06-09T13:20:59Z
dc.date.issued2021-05-22
dc.identifier.urihttp://hdl.handle.net/10713/15949
dc.description.abstractPneumonic tularemia is a highly debilitating and potentially fatal disease caused by inhalation of Francisella tularensis. Most of our current understanding of its pathogenesis is based on the highly virulent F. tularensis subsp. tularensis strain SCHU S4. However, multiple sources of SCHU S4 have been maintained and propagated independently over the years, potentially generating genetic variants with altered virulence. In this study, the virulence of four SCHU S4 stocks (NR-10492, NR-28534, NR-643 from BEI Resources and FTS-635 from Battelle Memorial Institute) along with another virulent subsp. tularensis strain, MA00-2987, were assessed in parallel. In the Fischer 344 rat model of pneumonic tularemia, NR-643 and FTS-635 were found to be highly attenuated compared to NR-10492, NR-28534, and MA00-2987. In the NZW rabbit model of pneumonic tularemia, NR-643 caused morbidity but not mortality even at a dose equivalent to 500x the LD50 for NR-10492. Genetic analyses revealed that NR-10492 and NR-28534 were identical to each other, and nearly identical to the reference SCHU S4 sequence. NR-643 and FTS-635 were identical to each other but were found to have nine regions of difference in the genomic sequence when compared to the published reference SCHU S4 sequence. Given the genetic differences and decreased virulence, NR-643/FTS-635 should be clearly designated as a separate SCHU S4 substrain and no longer utilized in efficacy studies to evaluate potential vaccines and therapeutics against tularemia.en_US
dc.description.urihttps://doi.org/10.3390/pathogens10060638en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofPathogens (Basel, Switzerland)en_US
dc.subjectFrancisella tularensisen_US
dc.subjectSCHU S4en_US
dc.subjectattenuationen_US
dc.subjectrabbitsen_US
dc.subjectratsen_US
dc.subjectsubstrainen_US
dc.subjectvirulenceen_US
dc.titleIdentification of an Attenuated Substrain of SCHU S4 by Phenotypic and Genotypic Analysesen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/pathogens10060638
dc.identifier.pmid34067337
dc.source.volume10
dc.source.issue6
dc.source.countrySwitzerland


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