title: Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen.
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.
authors.affiliation: Department of Microbiology, & Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. pwotoole@ucc.ie
authors.forename: Paul W
authors.initials: PW
authors.lastname: O'Toole
authors.forename: William J
authors.initials: WJ
authors.lastname: Snelling
authors.forename: Carlos
authors.initials: C
authors.lastname: Canchaya
authors.forename: Brian M
authors.initials: BM
authors.lastname: Forde
authors.forename: Kim R
authors.initials: KR
authors.lastname: Hardie
authors.forename: Christine
authors.initials: C
authors.lastname: Josenhans
authors.forename: Robert Lj
authors.initials: RLj
authors.lastname: Graham
authors.forename: Geoff
authors.initials: G
authors.lastname: McMullan
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Eugenio
authors.initials: E
authors.lastname: Belda
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004269:DNA, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D023281:Genomics; D045502:Helicobacter mustelae / Q000235:genetics* / Q000472:pathogenicity; D016480:Helicobacter pylori / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D020543:Proteome / Q000235:genetics*; D040901:Proteomics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D020543:Proteome