Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies

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Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies

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dc.contributor.author Champion, Mia D. en_GB
dc.contributor.author Zeng, Qiandong en_GB
dc.contributor.author Nix, Eli B. en_GB
dc.contributor.author Nano, Francis E. en_GB
dc.contributor.author Keim, Paul en_GB
dc.contributor.author Kodira, Chinnappa D. en_GB
dc.contributor.author Borowsky, Mark en_GB
dc.contributor.author Young, Sarah en_GB
dc.contributor.author Koehrsen, Michael en_GB
dc.contributor.author Engels, Reinhard en_GB
dc.contributor.author Pearson, Matthew en_GB
dc.contributor.author Howarth, Clint en_GB
dc.contributor.author Larson, Lisa en_GB
dc.contributor.author White, Jared en_GB
dc.contributor.author Alvarado, Lucia en_GB
dc.contributor.author Forsman, Mats en_GB
dc.contributor.author Bearden, Scott W. en_GB
dc.contributor.author Sjöstedt, Anders en_GB
dc.contributor.author Titball, Richard W. en_GB
dc.contributor.author Michell, Stephen L. en_GB
dc.contributor.author Birren, Bruce en_GB
dc.contributor.author Galagan, James en_GB
dc.date.accessioned 2010-03-16T15:17:42Z en_GB
dc.date.accessioned 2011-01-25T11:47:15Z en_US
dc.date.accessioned 2013-03-20T14:50:37Z
dc.date.issued 2009 en_GB
dc.description.abstract Tularemia 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.citation 5 (5), article e1000459 en_GB
dc.identifier.doi 10.1371/journal.ppat.1000459 en_GB
dc.identifier.uri http://hdl.handle.net/10036/94358 en_GB
dc.language.iso en en_GB
dc.publisher Public Library of Science (PLoS) en_GB
dc.relation.url http://dx.doi.org/10.1371/journal.ppat.1000459 en_GB
dc.title Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies en_GB
dc.type Article en_GB
dc.date.available 2010-03-16T15:17:42Z en_GB
dc.date.available 2011-01-25T11:47:15Z en_US
dc.date.available 2013-03-20T14:50:37Z
dc.identifier.issn 1553-7366 en_GB
dc.identifier.issn 1553-7374 en_GB
dc.description Copyright © 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.journal PLoS Pathogens en_GB


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