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


CONCLUSIONS
These isolates are deprived of the main H. pylori virulence factors characterized previously, but are nonetheless associated with gastric neoplasia.
Institut Pasteur, Unité postulante de Pathogenèse de Helicobacter, Paris, France.
Jean-Michel
JM
Thiberge
Caroline
C
Boursaux-Eude
Philippe
P
Lehours
Marie-Agnès
MA
Dillies
Sophie
S
Creno
Jean-Yves
JY
Coppée
Zoé
Z
Rouy
Aurélie
A
Lajus
Laurence
L
Ma
Christophe
C
Burucoa
Anne
A
Ruskoné-Foumestraux
Anne
A
Courillon-Mallet
Hilde
H
De Reuse
Ivo Gomperts
IG
Boneca
Dominique
D
Lamarque
Francis
F
Mégraud
Jean-Charles
JC
Delchier
Claudine
C
Médigue
Christiane
C
Bouchier
Agnès
A
Labigne
Josette
J
Raymond
D001426:Bacterial Proteins / Q000235:genetics; D016000:Cluster Analysis; D004381:Duodenal Ulcer / Q000382:microbiology; D019143:Evolution, Molecular; D005756:Gastritis / Q000382:microbiology; D020869:Gene Expression Profiling; D016680:Genome, Bacterial / Q000235:genetics*; D044404:Genomic Islands / Q000235:genetics; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D007410:Intestinal Diseases / Q000382:microbiology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000382:microbiology*; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010802:Phylogeny; D013045:Species Specificity
D001426:Bacterial Proteins