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PMID: 15102759 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

In vitro and in vivo characterization of Helicobacter hepaticus cytolethal distending toxin mutants.

Infection and immunity ·Vol. 72 ·No. 5 ·2004-05-00 ·Pages 2521-7

Young VB, Knox KA, Pratt JS, Cortez JS, Mansfield LS, Rogers AB, Fox JG, Schauer DB

Abstract

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.

MeSH Terms
Animals Bacterial Toxins/genetics,toxicity Colitis/etiology,pathology Female Genes, Bacterial HeLa Cells Helicobacter Infections/etiology,pathology Helicobacter hepaticus/genetics,pathogenicity Humans In Vitro Techniques Interleukin-10/deficiency,genetics Mice Mice, Inbred C57BL Mice, Knockout Multigene Family Mutagenesis, Insertional Mutation
Chemicals
Bacterial Toxins cytolethal distending toxin Interleukin-10
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Young Vincent B
Department of Microbiology and Molecular Genetics, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA. [email protected]
Knox Kimberly A
Pratt Jason S
Cortez Jennifer S
Mansfield Linda S
Rogers Arlin B
Fox James G
Schauer David B
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.72.5.2521-2527.2004
Email
[email protected]
Published
2004-05-00
Pages
2521-7
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC387909
Subset
IM
Grants
NIDDK NIH HHS · R01 DK052413 · United States
NCI NIH HHS · CA67529 · United States
NIAID NIH HHS · AI50952 · United States
NIAID NIH HHS · R01 AI050952 · United States
NIDDK NIH HHS · DK52413 · United States
NCI NIH HHS · R01 CA067529 · United States
NIDDK NIH HHS · R56 DK052413 · United States
External Links
PubMed source DOI: 10.1128/IAI.72.5.2521-2527.2004 PMC Full Text View journal details
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