Sequence Divergence and Conservation in Genomes of Helicobacter cetorum Strains from a Dolphin and a Whale

Abstract

Background and ObjectivesStrains of Helicobacter cetorum have been cultured from several marine mammals and have been found to be closely related in 16 S rDNA sequence to the human gastric pathogen H. pylori, but their genomes were not characterized further.MethodsThe genomes of H. cetorum strains from a dolphin and a whale were sequenced completely using 454 technology and PCR and capillary sequencing.ResultsThese genomes are 1.8 and 1.95 mb in size, some 7–26% larger than H. pylori genomes, and differ markedly from one another in gene content, and sequences and arrangements of shared genes. However, each strain is more related overall to H. pylori and its descendant H. acinonychis than to other known species. These H. cetorum strains lack cag pathogenicity islands, but contain novel alleles of the virulence-associated vacuolating cytotoxin (vacA) gene. Of particular note are (i) an extra triplet of vacA genes with ≤50% protein-level identity to each other in the 5′ two-thirds of the gene needed for host factor interaction; (ii) divergent sets of outer membrane protein genes; (iii) several metabolic genes distinct from those of H. pylori; (iv) genes for an iron-cofactored urease related to those of Helicobacter species from terrestrial carnivores, in addition to genes for a nickel co-factored urease; and (v) members of the slr multigene family, some of which modulate host responses to infection and improve Helicobacter growth with mammalian cells.ConclusionsOur genome sequence data provide a glimpse into the novelty and great genetic diversity of marine helicobacters. These data should aid further analyses of microbial genome diversity and evolution and infection and disease mechanisms in vast and often fragile ocean ecosystems.

Macroevolution of gastric Helicobacter species unveils interspecies admixture and time of divergence

“…This suggests that H. pylori has probably been acquired via a single-host jump from an unknown, non-human animal host since the stomachs of many animals are also infected by diverse species of Helicobacter. The closest relatives of H. pylori are H. acinonychis from wild felines, which has arisen through a host jump from humans [12], and H. cetorum from dolphins and whales [13]. Genetically much more distinct from H. pylori are the Helicobacter species naturally colonizing the stomach of domestic animals (including cats, dogs, and pigs) which have been designated as the non-H. pylori Helicobacter species (NHPH) group [14].…”

Divergence between the Highly Virulent Zoonotic Pathogen Helicobacter heilmannii and Its Closest Relative, the Low-Virulence “Helicobacter ailurogastricus” sp. nov

“…One of the major protein toxins secreted by H. pylori is the vacuolating cytotoxin A (VacA), which belongs to an additional family of OMPs called autotransporters (39). The VacA toxin binds to host cells and is internalized, causing severe "vacuolation" characterized by the accumulation of large vesicles that possess hallmarks of both late endosomes and early lysosomes (40) (15). Additionally, H. pylori contains three genes annotated as putative vacA paralogs, because the C-terminal autotransporter domains of the proteins they encode show approximately 30% identity to that of VacA.…”

Comparative Genomics ofH. pyloriand Non-PyloriHelicobacterSpecies to Identify New Regions Associated with Its Pathogenicity and Adaptability

“…The natural hosts of H. canis, H. bizzozeronii, H. Canadensis, H. felis, H. pullorum , and H. suis are mammals or birds, including pig, cat, dog, and geese. At the same time, the above six NHPS were also found to associate with gastric disease in humans [48–51]. H. acinonychis, H. ailurogastricus, H. bilis, H. cetorum, H. hepaticus, H. himalayensis, H. macacae, H. mustelae, H. pametensis , and H. typhlonius were isolated from nonhuman sources only, which had not been reported in human infection before [52–54].…”