title: The complete genome sequence of Francisella tularensis, the causative agent of tularemia.
abstract: Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.
authors.affiliation: Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Larsson
authors.forename: Petra C F
authors.initials: PC
authors.lastname: Oyston
authors.forename: Patrick
authors.initials: P
authors.lastname: Chain
authors.forename: May C
authors.initials: MC
authors.lastname: Chu
authors.forename: Melanie
authors.initials: M
authors.lastname: Duffield
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Fuxelius
authors.forename: Emilio
authors.initials: E
authors.lastname: Garcia
authors.forename: Greger
authors.initials: G
authors.lastname: Hälltorp
authors.forename: Daniel
authors.initials: D
authors.lastname: Johansson
authors.forename: Karen E
authors.initials: KE
authors.lastname: Isherwood
authors.forename: Peter D
authors.initials: PD
authors.lastname: Karp
authors.forename: Eva
authors.initials: E
authors.lastname: Larsson
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Stephen
authors.initials: S
authors.lastname: Michell
authors.forename: Joann
authors.initials: J
authors.lastname: Prior
authors.forename: Richard
authors.initials: R
authors.lastname: Prior
authors.forename: Stephanie
authors.initials: S
authors.lastname: Malfatti
authors.forename: Anders
authors.initials: A
authors.lastname: Sjöstedt
authors.forename: Kerstin
authors.initials: K
authors.lastname: Svensson
authors.forename: Nick
authors.initials: N
authors.lastname: Thompson
authors.forename: Lisa
authors.initials: L
authors.lastname: Vergez
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Wagg
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
authors.forename: Luther E
authors.initials: LE
authors.lastname: Lindler
authors.forename: Siv G E
authors.initials: SG
authors.lastname: Andersson
authors.forename: Mats
authors.initials: M
authors.lastname: Forsman
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D001483:Base Sequence; D004251:DNA Transposable Elements; D005604:Francisella tularensis / Q000235:genetics* / Q000254:growth & development; D016680:Genome, Bacterial; D044404:Genomic Islands; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D014774:Virulence / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D007501:Iron