Persistent Helicobacter pullorum colonization in C57BL/6NTac mice: a new mouse model for an emerging zoonosis.
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 (n=36) 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 µg 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.
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Michelle L
ML
Turk
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Laura D
LD
Cacioppo
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Zhongming
Z
Ge
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Zeli
Z
Shen
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Mark T
MT
Whary
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nicola
N
Parry
Taconic Inc., Hudson, NY 12534, USA.
Samuel R
SR
Boutin
Harlan Laboratories, Indianapolis, IN, USA.
Hilton J
HJ
Klein
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
James G
JG
Fox
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002432:Cecum / Q000382:microbiology; D002645:Chickens; D002908:Chronic Disease; D003106:Colon / Q000382:microbiology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000382:microbiology; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D015047:Zoonoses / Q000382:microbiology*
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G