The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus

doi:10.1073/pnas.1332093100

The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus

^*Institute of Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany; ^‡MWG Biotech AG, Anzinger Strasse 7a, D-85560 Ebersberg, Germany; ^**GeneData AG, Postfach 254, CH-4016 Basel, Switzerland; ^¶Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139; and ^∥School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia

Edited by John J. Mekalanos, Harvard Medical School, Boston, MA (received for review March 4, 2003)

Abstract

Helicobacter hepaticus causes chronic hepatitis and liver cancer in mice. It is the prototype enterohepatic Helicobacter species and a close relative of Helicobacter pylori, also a recognized carcinogen. Here we report the complete genome sequence of H. hepaticus ATCC51449. H. hepaticus has a circular chromosome of 1,799,146 base pairs, predicted to encode 1,875 proteins. A total of 938, 953, and 821 proteins have orthologs in H. pylori, Campylobacter jejuni, and both pathogens, respectively. H. hepaticus lacks orthologs of most known H. pylori virulence factors, including adhesins, the VacA cytotoxin, and almost all cag pathogenicity island proteins, but has orthologs of the C. jejuni adhesin PEB1 and the cytolethal distending toxin (CDT). The genome contains a 71-kb genomic island (HHGI1) and several genomic islets whose G+C content differs from the rest of the genome. HHGI1 encodes three basic components of a type IV secretion system and other virulence protein homologs, suggesting a role of HHGI1 in pathogenicity. The genomic variability of H. hepaticus was assessed by comparing the genomes of 12 H. hepaticus strains with the sequenced genome by microarray hybridization. Although five strains, including all those known to have caused liver disease, were indistinguishable from ATCC51449, other strains lacked between 85 and 229 genes, including large parts of HHGI1, demonstrating extensive variation of genome content within the species.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: ssuerbaum{at}hygiene.uniwuerzburg.de.
↵ § Present address: GenoServ, D-69221 Heidelberg, Germany.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AE017125). The annotated sequence and further information are available at www.THE-MWG.com.