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dc.contributor.authorChampion, Mia D.en_GB
dc.contributor.authorZeng, Qiandongen_GB
dc.contributor.authorNix, Eli B.en_GB
dc.contributor.authorNano, Francis E.en_GB
dc.contributor.authorKeim, Paulen_GB
dc.contributor.authorKodira, Chinnappa D.en_GB
dc.contributor.authorBorowsky, Marken_GB
dc.contributor.authorYoung, Sarahen_GB
dc.contributor.authorKoehrsen, Michaelen_GB
dc.contributor.authorEngels, Reinharden_GB
dc.contributor.authorPearson, Matthewen_GB
dc.contributor.authorHowarth, Clinten_GB
dc.contributor.authorLarson, Lisaen_GB
dc.contributor.authorWhite, Jareden_GB
dc.contributor.authorAlvarado, Luciaen_GB
dc.contributor.authorForsman, Matsen_GB
dc.contributor.authorBearden, Scott W.en_GB
dc.contributor.authorSjöstedt, Andersen_GB
dc.contributor.authorTitball, Richard W.en_GB
dc.contributor.authorMichell, Sen_GB
dc.contributor.authorBirren, Bruceen_GB
dc.contributor.authorGalagan, Jamesen_GB
dc.date.accessioned2010-03-16T15:17:42Zen_GB
dc.date.accessioned2011-01-25T11:47:15Zen_GB
dc.date.accessioned2013-03-20T14:50:37Z
dc.date.issued2009en_GB
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_GB
dc.identifier.citation5 (5), article e1000459en_GB
dc.identifier.doi10.1371/journal.ppat.1000459en_GB
dc.identifier.urihttp://hdl.handle.net/10036/94358en_GB
dc.language.isoenen_GB
dc.publisherPublic Library of Science (PLoS)en_GB
dc.relation.urlhttp://dx.doi.org/10.1371/journal.ppat.1000459en_GB
dc.titleComparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspeciesen_GB
dc.typeArticleen_GB
dc.date.available2010-03-16T15:17:42Zen_GB
dc.date.available2011-01-25T11:47:15Zen_GB
dc.date.available2013-03-20T14:50:37Z
dc.identifier.issn1553-7366en_GB
dc.identifier.issn1553-7374en_GB
dc.descriptionCopyright © 2009 Champion et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_GB
dc.identifier.journalPLoS Pathogensen_GB


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