Helicobacter hepaticus Cholesterol-α-glucosyltransferase is Essential for Establishing Colonization in Male A/JCr Mice
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Fox_Helicobacter hepaticus.pdf
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Author(s)
Ge, Zhongming
Feng, Yan
Muthupalani, Sureshkumar
Whary, Mark T.
Versalovic, James
Fox, James G.
Date Issued
May 2014
Journal
Helicobacter
Publisher
Wiley Blackwell
Citation
Ge, Zhongming, Yan Feng, Sureshkumar Muthupalani, Mark T. Whary, James Versalovic, and James G. Fox. “ Helicobacter Hepaticus Cholesterol-α-Glucosyltransferase Is Essential for Establishing Colonization in Male A/JCr Mice .” Helicobacter 19, no. 4 (May 23, 2014): 280–288.
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Author's final manuscript
Abstract
Background
Helicobacter pylori cholesterol-α-glucosyltransferase (cgt) is essential for survival of H. pylori in mice. Enterohepatic H. hepaticus, the cause of colonic and hepatocellular carcinoma in susceptible mouse strains, contains an ortholog of the H. pylori cgt. However, the role of cgt in the pathogenesis of H. hepaticus has not been investigated.
Materials and Methods
Two cgt-deficient isogenic mutants of wild-type H. hepaticus (WT) 3B1 were generated and used to inoculate male A/JCr mice. Cecal and hepatic colonization levels of the mutants and WT 3B1 as well as select inflammation-associated cytokines were measured by qPCR at 4 months postinoculation.
Results
Both mutants were undetectable in the cecum of any inoculated mice (10 per mutant) but were detected in two livers (one for each mutant); by contrast, 9 and 7 of 10 mice inoculated with WT 3B1 were qPCR positive in the ceca and livers, respectively. The mice inoculated with the mutants developed significantly less severe hepatic inflammation (p < .05) and also produced significantly lower hepatic mRNA levels of proinflammatory cytokines Ifn-γ (p < .01) and Tnf-α (p ≤ .02) as well as anti-inflammatory factors Il10 and Foxp3 compared with the WT 3B1-inoculated mice. Additionally, the WT 3B1-inoculated mice developed significantly higher Th1-associated IgG2a (p < .0001) and Th2-associated IgG1 responses (p < .0001) to H. hepaticus infection than mice dosed with isogenic cgt mutants.
Conclusion
Our data indicate that the cholesterol-α-glucosyltransferase is required for establishing colonization of the intestine and liver and therefore plays a critical role in the pathogenesis of H. hepaticus.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
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DOI of Published Version
https://doi.org/10.1111/hel.12135
