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dc.contributor.authorChampion, Mia D.en_US
dc.contributor.authorZeng, Qiandongen_US
dc.contributor.authorNix, Eli B.en_US
dc.contributor.authorNano, Francis E.en_US
dc.contributor.authorKeim, Paulen_US
dc.contributor.authorKodira, Chinnappa D.en_US
dc.contributor.authorBorowsky, Marken_US
dc.contributor.authorYoung, Sarahen_US
dc.contributor.authorKoehrsen, Michaelen_US
dc.contributor.authorEngels, Reinharden_US
dc.contributor.authorPearson, Matthewen_US
dc.contributor.authorHowarth, Clinten_US
dc.contributor.authorLarson, Lisaen_US
dc.contributor.authorWhite, Jareden_US
dc.contributor.authorAlvarado, Luciaen_US
dc.contributor.authorForsman, Matsen_US
dc.contributor.authorBearden, Scott W.en_US
dc.contributor.authorSjöstedt, Andersen_US
dc.contributor.authorTitball, Richarden_US
dc.contributor.authorMichell, Stephen L.en_US
dc.contributor.authorBirren, Bruceen_US
dc.contributor.authorGalagan, Jamesen_US
dc.date.accessioned2012-01-11T00:42:54Z
dc.date.available2012-01-11T00:42:54Z
dc.date.issued2009-5-29en_US
dc.identifier.citationChampion, Mia D., Qiandong Zeng, Eli B. Nix, Francis E. Nano, Paul Keim, Chinnappa D. Kodira, Mark Borowsky, Sarah Young, Michael Koehrsen, Reinhard Engels, Matthew Pearson, Clint Howarth, Lisa Larson, Jared White, Lucia Alvarado, Mats Forsman, Scott W. Bearden, Anders Sjöstedt, Richard Titball, Stephen L. Michell, Bruce Birren, James Galagan. "Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies" PLoS Pathogens 5(5): e1000459. (2009)en_US
dc.identifier.issn1553-7374en_US
dc.identifier.urihttp://hdl.handle.net/2144/3062
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. Author SummaryTularemia is a zoonotic disease that is widely disseminated throughout the Northern Hemisphere and is caused by different strain types of bacteria belonging to the genus Francisella. In general, Francisella tularensis subspecies are able to infect a wide range of mammals including humans and are often transmitted via insect vectors such as ticks. Depending on the strain and route of infection the disease may be fatal in humans. In order to better understand F. tularensis as an etiological agent as well as its potential as a biological weapon, we have completed draft sequence assemblies of five globally diverse strains. We have performed a comparative analysis of these sequences with other available public Francisella sequences of strains of differing virulence. Our analysis suggests that genome rearrangements and gene loss in specific Francisella subspecies may underlie the evolution of niche adaptation and virulence of this pathogen.en_US
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases; National Institutes of Health; Department of Health and Human Services (HHSN266200400001C)en_US
dc.language.isoenen_US
dc.publisherPublic Library of Science Pathogensen_US
dc.titleComparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspeciesen_US
dc.typearticleen_US
dc.identifier.doi10.1371/journal.ppat.1000459en_US
dc.identifier.pubmedid19478886en_US
dc.identifier.pmcid2682660en_US


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