Helicobacter pullorum is an enterohepatic Helicobacter species (EHS) that was recently reported as a naturally acquired infection in mice. Faecal samples from 18 out of 20 Brown Norway (BN) rats, housed in the same barrier as the H. pullorum-infected mice, were positive for H. pullorum using species-specific PCR. In addition, we determined whether H. pullorum was able to persistently colonize the gastrointestinal tract and/or biliary tree and elicit tissue inflammation as well as a serum IgG response in BN rats. Six (four male, two female) 6-week-old, H. pullorumnegative BN rats were orally dosed with 4¾10 8 c.f.u. of H. pullorum every other day for a total of three doses. At 2 weeks post-infection, all rats were H. pullorum-positive by faecal PCR. Five out of the six BN rats remained H. pullorum-positive for the entire 30 week study. PCR analysis of tissue collected at necropsy confirmed that the colon and caecum were the primary sites of H. pullorum colonization. Rats that were persistently colonized by H. pullorum had a sustained H. pullorum-specific IgG response measured by ELISA. Intestinal or hepatic pathology associated with H. pullorum infection was not noted. To our knowledge, this is the first report documenting that rats can be persistently colonized with an EHS that also infects humans.
Helicobacter pullorum, an enterohepatic Helicobacter species, is associated with gastroenteritis and hepatobiliary disease in humans and chickens. Recently, a novel H. pullorum outbreak in barrier-maintained rats and mice was described. In this study, persistence of infection and serological responses were further evaluated in H. pullorum-infected female C57BL/6NTac and C3H/HeNTac mice obtained from the barrier outbreak. C57BL/6NTac mice (n536) aged 10-58 weeks were confirmed to be chronically infected with H. pullorum by PCR or culture of caecum, colon and faeces, with no evidence of hepatic infection; two of three C3H/HeNTac mice cleared H. pullorum infection by 26 weeks of age. A quantitative PCR (qPCR) assay based on the cdtB gene specific to H. pullorum demonstrated that colonization was high in the caecum and colon at 10 4 -10 6 c.f.u. equivalents per mg host DNA, and decreased by several logs from 32 to 58 weeks of age. Infected mice were seropositive by ELISA, and H. pullorum-specific IgG levels decreased as colonization was lost over time in selected mice. Consistent with the lack of pathology associated with chronic infection of C57BL/6 mice with other murine enteric helicobacters, C57BL/6NTac and C3H/HeNTac mice infected with H. pullorum did not develop gross or histological lesions of the liver or gastrointestinal tract. The cdtB-based qPCR assay can be used in screening animals, food sources and environmental samples for H. pullorum, as this food-borne pathogen has zoonotic potential. These findings will also allow future studies in murine models to dissect potential pathogenic mechanisms for this emerging pathogen.
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