Cultivation of Whipple bacillus: the irony and the ecstasy

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been unable to propagate the microbe responsible for Whipple’s disease, despite many published and probably many more unpublished attempts.1 Evidence that a bacterium causes Whipple’s disease has accumulated in recent decades.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 On the basis of histology, investigators have suggested that these organisms propagate extracellularly,3 although intact organisms have been detected within several types of cells.4 A molecular phylogenetic approach provides evidence that the Whipple bacillus is a member of the actinomycete taxon of bacteria.5,6 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 Using both histological and molecular data, G Schoedon and colleagues8 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. It is ironic that the very cell believed to destroy the Whipple bacillus has been used to nurture its replication in the laboratory. This contradiction raises several new questions about the bacillus and how it interacts with the host. First, propagation of T whippelii within the artificial environment created in the laboratory may have little relevance to what occurs in natural infection. However, successful laboratory cultivation of T whippelii in macrophages suggests that some bacilli may survive and replicate in vivo within the macrophages of patients. If true, then the microbe may spread to other tissues as an intracellular passenger, and the macrophage may serve as a reservoir of infection, protecting T whippelii from immune defences. Whipple’s disease is notable for a disturbingly high rate of relapse despite months to years of antibiotic treatment. Can the microbe persist within macrophages of some patients, leading to subsequent reactivation disease, in a manner analogous to tuberculosis? On a more practical level, the in-vitro propagation of T whippelii paves the way for much needed antibiotic susceptibility testing, preparation of purified antigens for serological testing, and further characterisation of this enigmatic microorganism