Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies


Show simple item record Champion, Mia D. en_US Zeng, Qiandong en_US Nix, Eli B. en_US Nano, Francis E. en_US Keim, Paul en_US Kodira, Chinnappa D. en_US Borowsky, Mark en_US Young, Sarah en_US Koehrsen, Michael en_US Engels, Reinhard en_US Pearson, Matthew en_US Howarth, Clint en_US Larson, Lisa en_US White, Jared en_US Alvarado, Lucia en_US Forsman, Mats en_US Bearden, Scott W. en_US Sjöstedt, Anders en_US Titball, Richard en_US Michell, Stephen L. en_US Birren, Bruce en_US Galagan, James en_US 2012-01-11T00:42:54Z 2012-01-11T00:42:54Z 2009-5-29 en_US
dc.identifier.citation Champion, 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.issn 1553-7374 en_US
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. 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.sponsorship National Institute of Allergy and Infectious Diseases; National Institutes of Health; Department of Health and Human Services (HHSN266200400001C) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science Pathogens en_US
dc.title Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.ppat.1000459 en_US
dc.identifier.pubmedid 19478886 en_US
dc.identifier.pmcid 2682660 en_US

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