Open Access Research article

From array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma

Jean-Michel Thiberge1, Caroline Boursaux-Eude2, Philippe Lehours3, Marie-Agnès Dillies4, Sophie Creno5, Jean-Yves Coppée4, Zoé Rouy6, Aurélie Lajus6, Laurence Ma5, Christophe Burucoa7, Anne Ruskoné-Foumestraux8, Anne Courillon-Mallet9, Hilde De Reuse10, Ivo Gomperts Boneca1112, Dominique Lamarque13, Francis Mégraud3, Jean-Charles Delchier14, Claudine Médigue6, Christiane Bouchier5, Agnès Labigne10 and Josette Raymond1015*

Author Affiliations

1 Institut Pasteur, Génotypage des Pathogènes et Santé Publique, Paris, France

2 Institut Pasteur, PF4 Analyse et Intégration Génomiques, Paris, France

3 Université Victor Segalen, INSERM U853, Bordeaux, France

4 Institut Pasteur, PF2 Puces à ADN, Paris, France

5 Institut Pasteur, PF1 Génomique, Paris, France

6 CEA, Direction des Sciences du Vivant, Institut de Génomique, Genoscope & CNRS-UMR 8030, Laboratoire d'Analyse Bioinformatique en Génomique et Métabolisme, Evry, France

7 CHU de Poitiers, EA4331, LITEC, Bactériologie, Poitiers, France

8 Hôpital Saint Antoine, Paris, France

9 Hôpital Villeneuve Saint Georges, France

10 Institut Pasteur, Unité postulante de Pathogenèse de Helicobacter, Paris, France

11 Institut Pasteur, Groupe Biologie et génétique de la paroi bactérienne, Paris, France

12 INSERM, Groupe Avenir, Paris, France

13 Hôpital Hôtel Dieu, Paris, France

14 Hôpital Henri Mondor, Créteil, France

15 Université Paris Descartes, Faculté de Médecine, Hôpital Cochin, Paris, France

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BMC Genomics 2010, 11:368  doi:10.1186/1471-2164-11-368

Published: 10 June 2010

Abstract

Background

elicobacter pylori infection is associated with several gastro-duodenal inflammatory diseases of various levels of severity. To determine whether certain combinations of genetic markers can be used to predict the clinical source of the infection, we analyzed well documented and geographically homogenous clinical isolates using a comparative genomics approach.

Results

A set of 254 H. pylori genes was used to perform array-based comparative genomic hybridization among 120 French H. pylori strains associated with chronic gastritis (n = 33), duodenal ulcers (n = 27), intestinal metaplasia (n = 17) or gastric extra-nodal marginal zone B-cell MALT lymphoma (n = 43). Hierarchical cluster analyses of the DNA hybridization values allowed us to identify a homogeneous subpopulation of strains that clustered exclusively with cagPAI minus MALT lymphoma isolates. The genome sequence of B38, a representative of this MALT lymphoma strain-cluster, was completed, fully annotated, and compared with the six previously released H. pylori genomes (i.e. J99, 26695, HPAG1, P12, G27 and Shi470). B38 has the smallest H. pylori genome described thus far (1,576,758 base pairs containing 1,528 CDSs); it contains the vacAs2m2 allele and lacks the genes encoding the major virulence factors (absence of cagPAI, babB, babC, sabB, and homB). Comparative genomics led to the identification of very few sequences that are unique to the B38 strain (9 intact CDSs and 7 pseudogenes). Pair-wise genomic synteny comparisons between B38 and the 6 H. pylori sequenced genomes revealed an almost complete co-linearity, never seen before between the genomes of strain Shi470 (a Peruvian isolate) and B38.

Conclusion

These isolates are deprived of the main H. pylori virulence factors characterized previously, but are nonetheless associated with gastric neoplasia.