Identification of the uncultured bacillus of Whipple's disease

N Engl J Med. 1992 Jul 30;327(5):293-301. doi: 10.1056/NEJM199207303270501.


Background: Whipple's disease is a systemic disorder known for 85 years to be associated with an uncultured, and therefore unidentified, bacillus.

Methods: We used a molecular genetic approach to identify this organism. The bacterial 16S ribosomal RNA (rRNA) sequence was amplified directly from tissues of five unrelated patients with Whipple's disease by means of the polymerase chain reaction, first with broad-range primers and then with specific primers. We determined and analyzed the nucleotide sequence of the amplification products.

Results: A unique 1321-base bacterial 16S rRNA sequence was amplified from duodenal tissue of one patient. This sequence indicated the presence of a previously uncharacterized organism. We then detected this sequence in tissues from all 5 patients with Whipple's disease, but in none of those from 10 patients without the disorder. According to phylogenetic analysis, this bacterium is a gram-positive actinomycete that is not closely related to any known genus.

Conclusions: We have identified the uncultured bacillus associated with Whipple's disease. The phylogenetic relations of this bacterium, its distinct morphologic characteristics, and the unusual features of the disease are sufficient grounds for naming this bacillus Tropheryma whippelii gen. nov. sp. nov. Our findings also provide a basis for a specific diagnostic test for this organism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actinobacteria / genetics
  • Actinobacteria / isolation & purification*
  • Adult
  • Base Sequence
  • Duodenum / chemistry
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Bacterial / analysis
  • RNA, Ribosomal, 16S / analysis
  • Whipple Disease / microbiology*


  • RNA, Bacterial
  • RNA, Ribosomal, 16S