Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen.
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.
O'Toole
Paul W
PW
Department of Microbiology, & Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. pwotoole@ucc.ie
Snelling
William J
WJ
Canchaya
Carlos
C
Forde
Brian M
BM
Hardie
Kim R
KR
Josenhans
Christine
C
Graham
Robert Lj
RLj
McMullan
Geoff
G
Parkhill
Julian
J
Belda
Eugenio
E
Bentley
Stephen D
SD
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
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D020543:Proteome