Cultivation of Whipple bacillus: the irony and the ecstasy

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For 90 years investigators (including George Whipple) have been unable to propagate the microbe responsible for Whipple's disease, despite many published and probably many more unpublished attempts. 1 Whipple GH A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Johns Hopkins Hosp Bull. 1907; 18: 382-391 Google Scholar Evidence that a bacterium causes Whipple's disease has accumulated in recent decades. Light and electron microscopy show rod-shaped bacilli in the affected tissues of these patients, usually free in the lamina propria of the small bowel but also as partly degraded structures within macrophage vacuoles. 2 Trier JS Phelps PC Eidelman S Rubin CE Whipple's disease: light and electron microscopic correlation of jejunal mucosal histology with antibiotic treatment and clinical status. Gastroenterology. 1965; 48: 684-707 PubMed Scopus (95) Google Scholar On the basis of histology, investigators have suggested that these organisms propagate extracellularly, 3 Silva MT Macedo PM Moura NJ Ultrastructure of bacilli and the bacillary origin of the macrophagic inclusions in Whipple's disease. J Gen Microbiol. 1985; 131: 1001-1013 PubMed Google Scholar although intact organisms have been detected within several types of cells. 4 Dobbins W Kawanishi H Bacillary characteristics in Whipple's disease: an electron microscopic study. Gastroenterology. 1981; 80: 1468-1475 PubMed Scopus (77) Google Scholar A molecular phylogenetic approach provides evidence that the Whipple bacillus is a member of the actinomycete taxon of bacteria. 5 Relman DA Schmidt TM MacDermott RP Falkow S Identification of the uncultured bacillus of Whipple's disease. N Engl J Med. 1992; 327: 293-301 Crossref PubMed Scopus (1031) Google Scholar , 6 Wilson KH Blitchington R Frothingham R Wilson JA Phylogeny of the Whipple's-disease-associated bacterium. Lancet. 1991; 338: 474-475 Summary PubMed Scopus (302) Google Scholar DNA from this microbe, unofficially named Tropheryma whippelii, is almost invariably present in patients who have Whipple's disease, but disappears with effective antibiotic treatment. 7 Ramzan NN Loftus EJ Burgart LJ et al. Diagnosis and monitoring of Whipple disease by polymerase chain reaction. Ann Intern Med. 1997; 126: 520-527 Crossref PubMed Scopus (209) Google Scholar Using both histological and molecular data, G Schoedon and colleagues 8 Schoedon G Goldenberger D Forrer R et al. Deactivation of macrophages with IL-4 is the key to the isolation of Tropheryma whippelii. J Infect Dis. 1997; 176: 672-677 Crossref PubMed Scopus (156) Google Scholar now provide evidence of the successful propagation of T whippelii in cell culture. Interleukin-4 (IL-4) was critical for rendering peripheral blood monocytes and monoblastic cell-lines permissive for intracellular growth of the organism.