The HHGI1 Genomic Island

H. hepaticus lacks orthologues of the H. pylori cag PAI. However, we identified a large chromosomal region with a conspicuously lower G+C content than the rest of the genome, indicating acquisition by horizontal gene transfer. The 70-kbp region also showed other features suggestive of a PAI, such as a P4-like phage integrase, a very high density of genes lacking homologues in other organisms, and three genes encoding proteins with homology to components of type IV secretion systems, such as the Tpilus system of Agrobacterium tumefaciens (VirB10, VirB4, VirD4). Several observations suggest an involvement of the HHGI1 island in the virulence of H. hepaticus. For example, genome comparisons of clinical isolates of H. hepaticus with DNA microarrays have shown that many strains lack the island, or parts of it [4]. These isolates have never been associated with hepatitis or cancer, suggesting a lower pathogenic potential of island-deficient strains. Experiments with isogenic mutants lacking parts of the island are now in progress to confirm the role of the island, and in particular the putative type IV secretion system in H. hepaticus-induced pathology.

14.4 Genome Comparisons of Gastric and Enterohepatic Helicobacter Species with Related Bacteria | 307 14.3.2

Other Putative H. hepaticus Virulence Factors

Currently, very little is known about H. hepaticus virulence factors. Urease is thought to be essential for its colonization (S. Ragnum and D. B. Schauer, unpublished data). H. hepaticus produces cytolethal distending toxin (CDT), a multifunctional toxin found in a number of pathogens, such as Campylobacter jejuni, some Escherichia coli strains, Actinobacillus actinomycetemcomitans, and Haemophilus ducreyi. H. hepaticus mutants deficient in CDT synthesis have been generated and induced less inflammation than did the corresponding wildtype strain in a mouse model of inflammatory bowel disease [66]. Further putative virulence factors include a homologue of the Campylobacter jejuni adhesin PEB-1 [4].

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