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Open Access Research article

Comparative genomic analysis of Tropheryma whipplei strains reveals that diversity among clinical isolates is mainly related to the WiSP proteins

My-Van La1, Nicolas Crapoulet1, Pascal Barbry23, Didier Raoult1 and Patricia Renesto1*

Author Affiliations

1 Unité des Rickettsies, CNRS-UMR6020, IFR48, Faculté de Médecine, 27 Bd Jean Moulin, Marseille, F13385, France

2 CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR6097, Sophia Antipolis, F06560, France

3 Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR6097, Sophia Antipolis, F06560, France

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BMC Genomics 2007, 8:349  doi:10.1186/1471-2164-8-349

Published: 2 October 2007

Abstract

Background

The aim of this study was to analyze the genomic diversity of several Tropheryma whipplei strains by microarray-based comparative genomic hybridization. Fifteen clinical isolates originating from biopsy samples recovered from different countries were compared with the T. whipplei Twist strain. For each isolate, the genes were defined as either present or absent/divergent using the GACK analysis software. Genomic changes were then further characterized by PCR and sequencing.

Results

The results revealed a limited genetic variation among the T. whipplei isolates, with at most 2.24% of the probes exhibiting differential hybridization against the Twist strain. The main variation was found in genes encoding the WiSP membrane protein family. This work also demonstrated a 19.2 kb-pair deletion within the T. whipplei DIG15 strain. This deletion occurs in the same region as the previously described large genomic rearrangement between Twist and TW08/27. Thus, this can be considered as a major hot-spot for intra-specific T. whipplei differentiation. Analysis of this deleted region confirmed the role of WND domains in generating T. whipplei diversity.

Conclusion

This work provides the first comprehensive genomic comparison of several T. whipplei isolates. It reveals that clinical isolates originating from various geographic and biological sources exhibit a high conservation rate, indicating that T. whipplei rarely interacts with exogenous DNA. Remarkably, frequent inter-strain variations were dicovered that affected members of the WiSP family.