Sequencing and analysis of the genome of the Whipple's disease bacterium Tropheryma whipplei.
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.
Bentley
Stephen D
SD
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Maiwald
Matthias
M
Murphy
Lee D
LD
Pallen
Mark J
MJ
Yeats
Corin A
CA
Dover
Lynn G
LG
Norbertczak
Halina T
HT
Besra
Gurdyal S
GS
Quail
Michael A
MA
Harris
David E
DE
von Herbay
Axel
A
Goble
Arlette
A
Rutter
Simon
S
Squares
Robert
R
Squares
Stephen
S
Barrell
Bart G
BG
Parkhill
Julian
J
Relman
David A
DA
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*