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Background The bacterium Helicobacter pylori is associated with ulcers and the development of gastric cancer. Several genes, including cytotoxin-associated gene A ( CagA) and vacuolating cytotoxin A ( VacA), are associated with increased gastric cancer risk. Some strains of H. pylori also contain sequences related to bacteriophage phi HP33; however, the significance of these phage-related sequences remains unknown. Materials and Methods We assessed the extent to which phi HP33-related sequences are present in 335 H. pylori strains using homology searches then mapped shared genes between phi HP33 and H. pylori strains onto an existing phylogeny. Results One hundred and twenty-one H. pylori strains contain phage orthologous sequences, and the presence of the phage-related sequences correlates with the presence of CagA and VacA. Mapping of the phage orthologs onto a phylogeny of H. pylori is consistent with the hypothesis that these genes were acquired by horizontal gene transfer. Conclusions phi HP33 phage orthologous sequences might be of significance in understanding virulence of different H. pylori strains. [ABSTRACT FROM AUTHOR]