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Infection and Immunity, May 2004, p. 2521-2527, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2521-2527.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Characterization of Helicobacter hepaticus Cytolethal Distending Toxin Mutants

Vincent B. Young,1,2,3* Kimberly A. Knox,4 Jason S. Pratt,1,3 Jennifer S. Cortez,2,3 Linda S. Mansfield,1,3 Arlin B. Rogers,4 James G. Fox,4,5 and David B. Schauer4,5

Department of Microbiology and Molecular Genetics,1 Infectious Diseases Unit, Department of Internal Medicine,2 National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824,3 Division of Comparative Medicine,4 Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 021395

Received 16 December 2003/ Returned for modification 16 January 2004/ Accepted 21 January 2004

Helicobacter hepaticus expresses a member of the cytolethal distending toxin (CDT) family of bacterial cytotoxins. To investigate the role of CDT in the pathogenesis of H. hepaticus, transposon mutagenesis was used to generate a series of isogenic mutants in and around the cdtABC gene cluster. An H. hepaticus transposon mutant with a disrupted cdtABC coding region no longer produced CDT activity. Conversely, a transposon insertion outside of the cluster did not affect the CDT activity. An examination of these mutants demonstrated that CDT represents the previously described granulating cytotoxin in H. hepaticus. Challenge of C57BL/6 interleukin 10–/– mice with isogenic H. hepaticus mutants revealed that CDT expression is not required for colonization of the murine gut. However, a CDT-negative H. hepaticus mutant had a significantly diminished capacity to induce lesions in this murine model of inflammatory bowel disease.

* Corresponding author. Mailing address: Room B42 Food Safety and Toxicology Building, Michigan State University, East Lansing, MI 48824. Phone: (517) 432-3100. Fax: (517) 432-2310. E-mail: youngvi{at}msu.edu.

Editor: D. L. Burns

Infection and Immunity, May 2004, p. 2521-2527, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2521-2527.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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