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

dc.contributor.authorO'Toole, Paul W.
dc.contributor.authorSnelling, William J.
dc.contributor.authorCanchaya, Carlos
dc.contributor.authorForde, Brian M.
dc.contributor.authorHardie, Kim R.
dc.contributor.authorJosenhans, Christine
dc.contributor.authorGraham, Robert L.J.
dc.contributor.authorMcMullan, Geoff
dc.contributor.authorParkhill, Julian
dc.contributor.authorBelda, Eugenio
dc.contributor.authorBentley, Stephen D.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderDepartment of Agriculture, Fisheries and Food, Irelanden
dc.contributor.funderNorthern Ireland Centre of Excellence in Functional Genomicsen
dc.contributor.funderEuropean Union Program for Peace and Reconciliationen
dc.contributor.funderBundesministerium für Bildung und Forschung, Germanyde
dc.contributor.funderWellcome Trust, United Kingdomen
dc.description.abstractBackground: 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.en
dc.description.sponsorshipScience Foundation Ireland (SFI CSET); Science Foundation Ireland (PI awards); Department of Agriculture, Fisheries and Food, Ireland (FHRI Award to the Eldermet Project); European Union Program for Peace and Reconciliation (EU Technology Support for the Knowledge-Based Economy); Bundesministerium für Bildung und Forschung, Germany (ERAnet PathoGenomics)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.identifier.citationO'Toole, P. W., W. J. Snelling, et al. (2010). "Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen." BMC Genomics 11: 164. doi: 10.1186/1471-2164-11-164en
dc.identifier.journaltitleBMC Genomicsen
dc.publisherBioMed Centralen
dc.rights© 2010 O'Toole et al; licensee BioMed Central Ltd.en
dc.subjectHelicobacter mustelaeen
dc.subjectH. pylorien
dc.titleComparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogenen
dc.typeArticle (peer-reviewed)en
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