title: Sequencing and analysis of the genome of the Whipple's disease bacterium Tropheryma whipplei.
abstract: BACKGROUND
  Whipple's disease is a rare multisystem chronic infection, involving the intestinal tract as well as various other organs. The causative agent, Tropheryma whipplei, is a Gram-positive bacterium about which little is known. Our aim was to investigate the biology of this organism by generating and analysing the complete DNA sequence of its genome.
  
  
  METHODS
  We isolated and propagated T whipplei strain TW08/27 from the cerebrospinal fluid of a patient diagnosed with Whipple's disease. We generated the complete sequence of the genome by the whole genome shotgun method, and analysed it with a combination of automatic and manual bioinformatic techniques.
  
  
  RESULTS
  Sequencing revealed a condensed 925938 bp genome with a lack of key biosynthetic pathways and a reduced capacity for energy metabolism. A family of large surface proteins was identified, some associated with large amounts of non-coding repetitive DNA, and an unexpected degree of sequence variation.
  
  
  CONCLUSIONS
  The genome reduction and lack of metabolic capabilities point to a host-restricted lifestyle for the organism. The sequence variation indicates both known and novel mechanisms for the elaboration and variation of surface structures, and suggests that immune evasion and host interaction play an important part in the lifestyle of this persistent bacterial pathogen.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Matthias
authors.initials: M
authors.lastname: Maiwald
authors.forename: Lee D
authors.initials: LD
authors.lastname: Murphy
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pallen
authors.forename: Corin A
authors.initials: CA
authors.lastname: Yeats
authors.forename: Lynn G
authors.initials: LG
authors.lastname: Dover
authors.forename: Halina T
authors.initials: HT
authors.lastname: Norbertczak
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: David E
authors.initials: DE
authors.lastname: Harris
authors.forename: Axel
authors.initials: A
authors.lastname: von Herbay
authors.forename: Arlette
authors.initials: A
authors.lastname: Goble
authors.forename: Simon
authors.initials: S
authors.lastname: Rutter
authors.forename: Robert
authors.initials: R
authors.lastname: Squares
authors.forename: Stephen
authors.initials: S
authors.lastname: Squares
authors.forename: Bart G
authors.initials: BG
authors.lastname: Barrell
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: David A
authors.initials: DA
authors.lastname: Relman
mesh_terms: D005260:Female; D016678:Genome; D006094:Gram-Positive Bacteria / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D017422:Sequence Analysis, DNA; D008061:Whipple Disease / Q000235:genetics* / Q000382:microbiology*