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Open Access Highly Accessed Research article

Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen

Paul W O'Toole1*, William J Snelling2, Carlos Canchaya3, Brian M Forde1, Kim R Hardie4, Christine Josenhans5, Robert LJ Graham2, Geoff McMullan2, Julian Parkhill6, Eugenio Belda67 and Stephen D Bentley6

Author affiliations

1 Department of Microbiology, & Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

2 School of Biomedical Sciences, University of Ulster, Coleraine, County Londonderry, BT52 1SA, N. Ireland, UK

3 Department of Biochemistry, Genetics and Immunology, University of Vigo, 36310 Vigo, Spain

4 School of Molecular Medical Sciences, University of Nottingham, Centre for Biomolecular Sciences, Nottingham NG7 2RH, UK

5 Hannover Medical School, Department for Medical Microbiology and Hospital Epidemiology, Hannover, Germany

6 Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK

7 Current Address:Cavanilles Institute of Biodiversity and Evolutionary Biology, Department of Genetics, University of Valencia, Valencia, Spain

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Citation and License

BMC Genomics 2010, 11:164  doi:10.1186/1471-2164-11-164

Published: 10 March 2010

Abstract

Background

Helicobacter mustelae causes gastritis, ulcers and gastric cancer in ferrets and other mustelids. H. mustelae remains the only helicobacter other than H. pylori that causes gastric ulceration and cancer in its natural host. To improve understanding of H. mustelae pathogenesis, and the ulcerogenic and carcinogenic potential of helicobacters in general, we sequenced the H. mustelae genome, and identified 425 expressed proteins in the envelope and cytosolic proteome.

Results

The H. mustelae genome lacks orthologs of major H. pylori virulence factors including CagA, VacA, BabA, SabA and OipA. However, it encodes ten autotransporter surface proteins, seven of which were detected in the expressed proteome, and which, except for the Hsr protein, are of unknown function. There are 26 putative outer membrane proteins in H. mustelae, some of which are most similar to the Hof proteins of H. pylori. Although homologs of putative virulence determinants of H. pylori (NapA, plasminogen adhesin, collagenase) and Campylobacter jejuni (CiaB, Peb4a) are present in the H. mustelae genome, it also includes a distinct complement of virulence-related genes including a haemagglutinin/haemolysin protein, and a glycosyl transferase for producing blood group A/B on its lipopolysaccharide. The most highly expressed 264 proteins in the cytosolic proteome included many corresponding proteins from H. pylori, but the rank profile in H. mustelae was distinctive. Of 27 genes shown to be essential for H. pylori colonization of the gerbil, all but three had orthologs in H. mustelae, identifying a shared set of core proteins for gastric persistence.

Conclusions

The determination of the genome sequence and expressed proteome of the ulcerogenic species H mustelae provides a comparative model for H. pylori to investigate bacterial gastric carcinogenesis in mammals, and to suggest ways whereby cag minus H. pylori strains might cause ulceration and cancer.

The genome sequence was deposited in EMBL/GenBank/DDBJ under accession number FN555004.