1A) . Helicobacter canis strains NCTC 12740 (human-origin) , NCTC 12739 (dog-origin) , MIT 98-0152 (cat-origin) , and MIT 99-7633 (rhesus macaque-origin) were analyzed simultaneously KU 57788 for comparison. Sheep-origin H. canis isolates shared the same banding pattern by REP-PCR, indicating clonality, but were distinct from the control strains tested (Fig. 1B). All sheep-origin isolates were catalase, urease, and γ-glutamyl transpeptidase-negative, oxidase-positive, and did not reduce nitrate
to nitrite. Strains from other species shared the same biochemical profile, except that non-sheep strains were γ-glutamyl transpeptidase-positive. Because a previously reported H. canis strain was shown to produce cytolethal distending toxin, all isolates were evaluated for in vitro cytotoxicity. The sheep-origin PI3K inhibitor isolates did not induce cellular changes consistent with cytotoxicity. 16S rRNA sequencing and BLASTn analysis confirmed that the three sheep-origin isolates tested shared 99% identity with H. canis. A neighbor joining phylogenetic tree
was constructed based on sequence similarity (Fig. 1C). Sheep-origin H. canis isolates clustered with H. canis strains from other species, but were distinct from other enterohepatic Helicobacter species (EHS) previously isolated from sheep. In addition to H. canis, sheep have been shown to harbor EHS, namely, H. bilis (Flexispira taxon 2) and H. trogontum (Flexispira taxa 4 and 5) [19-21]. Two of these sheep-origin strains were associated with fetal hepatic necrosis and late-term abortion, a phenomenon that was later experimentally reproduced [21-23]. Helicobacter canis has 上海皓元 not been associated with a specific ovine disease syndrome, though
interestingly it has been isolated from a dog’s liver with active hepatitis . As no definitive connection has been established, the flock studied here has had several mummified and late-term dead fetuses born to ewes delivering multiple lambs. Also, the flock has historic exposure to dogs and cats. This study identifies sheep as a new and potentially important H. canis reservoir host that could promote direct zoonotic transmission or transmission via dogs or cats. Interestingly, a similar dynamic has been proposed to explain the high H. pylori prevalence in individuals with direct or indirect sheep or sheep dog exposure. Several prior reports showed 98% H. pylori prevalence in Sardinian  and Polish  shepherds by CagA ELISA and 13C urea breath test. Sheep contact also disproportionately increased H. pylori prevalence odds in Columbian children when measured by 13C urea breath test . These prior studies established sheep as a potential H. pylori reservoir and have fueled speculation that sheep may be a natural H. pylori host species.