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Infect. Immun. doi:10.1128/IAI.01091-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Rapid onset of ulcerative typhlocolitis in B6.129P2-IL10tm1Cgn (IL-10-/-) mice infected with Helicobacter trogontum is associated with decreased colonization of Altered Schaedler's Flora

M T Whary*, S J Danon, Y Feng, Z Ge, N Sundina, V Ng, N S Taylor, A B Rogers, and J G Fox

Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139 USA; CSIRO Molecular & Health Technologies, North Ryde, NSW, Australia 1670

* To whom correspondence should be addressed. Email: mwhary{at}mit.edu,


   Abstract

Infection with Helicobacter trogontum, a urease-positive helicobacter isolated from subclinically infected rats, was evaluated in B6.129P2-Il10tm1Cgn (IL-10-/-) and C57BL/6 (B6) mice. In a first experiment, IL-10-/- mice naturally infected with H. rodentium had subclinical typhlocolitis but developed severe diarrhea and loss of body condition with erosive to ulcerative typhlocolitis within 1 to 3 weeks of experimental infection with H. trogontum. A second experiment demonstrated that helicobacter-free IL-10-/- mice dosed with H. trogontum also developed severe clinical signs and typhlocolitis within 2-4 weeks whereas B6 mice colonized with H. trogontum were resistant to disease. A third experiment using helicobacter-free IL-10-/- mice dosed with H. trogontum resulted in acute morbidity and typhlocolitis within 8 days. Acute typhlocolitis was accompanied by signs of sepsis supported by degenerative hemograms and recovery of E. coli and Proteus spp. from the livers of infected mice. Quantitative PCR data revealed that H. rodentium and H. trogontum may compete for colonization of the lower bowel as H. trogontum established higher colonization levels in the absence of H. rodentium (p<0.003). H. trogontum-induced typhlocolitis was also associated with a significant decrease in the colonization levels of 5 of 8 anaerobes that comprise Altered Schaedler's Flora (p<0.002). These results demonstrate for the first time that H. rodentium infection in IL-10-/- mice caused subclinical typhlocolitis and infection with H. trogontum, with or without H. rodentium, induced a rapid onset, erosive to ulcerative typhlocolitis which impacted the normal anaerobic flora of the colon and increased the risk of sepsis.




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