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dc.contributor.authorChampion, Mia D.
dc.contributor.authorZeng, Qiandong
dc.contributor.authorNix, Eli B.
dc.contributor.authorNano, Francis E.
dc.contributor.authorKeim, Paul
dc.contributor.authorKodira, Chinnappa D.
dc.contributor.authorKoehrsen, Michael
dc.contributor.authorPearson, Matthew
dc.contributor.authorHowarth, Clint
dc.contributor.authorLarson, Lisa
dc.contributor.authorWhite, Jared
dc.contributor.authorAlvarado, Lucia
dc.contributor.authorForsman, Mats
dc.contributor.authorBearden, Scott W.
dc.contributor.authorSjöstedt, Anders
dc.contributor.authorTitball, Richard
dc.contributor.authorMichell, Stephen L.
dc.contributor.authorBirren, Bruce
dc.contributor.authorBorowsky, Mark L
dc.contributor.authorYoung, Sarah U.
dc.contributor.authorEngels, Reinhard
dc.contributor.authorGalagan, James E
dc.date.accessioned2011-05-16T23:31:26Z
dc.date.issued2009
dc.identifier.citationChampion, Mia D., Qiandong Zeng, Eli B. Nix, Francis E. Nano, Paul Keim, Chinnappa D. Kodira, Mark Borowsky, et al. 2009. Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies. PLoS Pathogens 5(5): e1000459.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4889577
dc.description.abstractTularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.1000459en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682660/pdf/en_US
dash.licenseLAA
dc.subjectcomputational biologyen_US
dc.subjectcomparative sequence analysisen_US
dc.subjectgenomicsen_US
dc.subjectevolutionary biologyen_US
dc.subjectbioinformaticsen_US
dc.subjectevolutionary and comparative geneticsen_US
dc.subjectmicrobial evolution and genomicsen_US
dc.subjectgenetics and genomicsen_US
dc.subjectcomparative genomicsen_US
dc.subjectgenetics of diseaseen_US
dc.subjectgenome projectsen_US
dc.subjectpopulation geneticsen_US
dc.subjectinfectious diseasesen_US
dc.subjectbacterial infectionsen_US
dc.subjectmicrobiologyen_US
dc.titleComparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspeciesen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorBorowsky, Mark L
dc.date.available2011-05-16T23:31:26Z
dash.affiliation.otherHMS^Geneticsen_US
dash.affiliation.otherSPH^Immunology and Infectious Diseases TPHen_US
dc.identifier.doi10.1371/journal.ppat.1000459*
dash.authorsorderedfalse
dash.contributor.affiliatedYoung, Sarah
dash.contributor.affiliatedEngels, Reinhard
dash.contributor.affiliatedBorowsky, Mark L
dash.contributor.affiliatedGalagan, James E.


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