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Genotyping reveals a wide heterogeneity of Tropheryma whipplei

¹ Unité des Rickettsies, IFR 48, CNRS UMR 6020, Faculté de Médecine, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France
² DRK Krankenhaus Neuwied, Germany
³ Universitätsklinik für Innere Medizin IV, Klinische Abteilung Gastroenterologie und Hepatologie, Medizinische Universität, Wien, Austria
⁴ Department of Internal Medicine, St Josef Hospital, Zel, Germany
⁵ Bio-Analytica AG, Maihofstrasse 95a, 6000 Luzern 6, Switzerland
⁶ Department of Medical Microbiology, University of Zurich, Zurich, Switzerland
⁷ Department of Infectious Diseases, Charité, Campus Benjamin Franklin, Berlin, Germany
⁸ Gastroenterology Unit, Fondazione IRCCS, Policlinico San Matteo, University of Pavia, Italy

Correspondence
Didier Raoult
didier.raoult{at}gmail.com

Tropheryma whipplei, the causative agent of Whipple's disease, is associated with various clinical manifestations as well as an asymptomatic carrier status, and it exhibits genetic heterogeneity. However, relationships that may exist between environmental and clinical strains are unknown. Herein, we developed an efficient genotyping system based on four highly variable genomic sequences (HVGSs) selected on the basis of genome comparison. We analysed 39 samples from 39 patients with Whipple's disease and 10 samples from 10 asymptomatic carriers. Twenty-six classic gastrointestinal Whipple's disease associated with additional manifestations, six relapses of classic Whipple's disease (three gastrointestinal and three neurological relapses), and seven isolated infections due to T. whipplei without digestive involvement (five endocarditis, one spondylodiscitis and one neurological infection) were included in the study. We identified 24 HVGS genotypes among 39 T. whipplei DNA samples from the patients and 10 T. whipplei DNA samples from the asymptomatic carriers. No significant correlation between HVGS genotypes and clinical manifestations of Whipple's disease, or asymptomatic carriers, was found for the 49 samples tested. Our observations revealed a high genetic diversity of T. whipplei strains that is apparently independent of geographical distribution and unrelated to bacterial pathogenicity. Genotyping in Whipple's disease may, however, be useful in epidemiological studies.

The GenBank/EMBL/DDBJ accession numbers for the HVGS marker sequences of T. whipplei are given in Table 1.

A table showing a summary of clinical manifestations of Whipple's disease patients and asymptomatic carriers together with T. whipplei genotypes, and dendrograms showing the phylogenetic organization of the 24 HVGS genotypes constructed using the neighbour-joining and parsimony methods, are available as supplementary data with the online version of this paper.