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

被引:107
作者
Young, VB
Knox, MA
Pratt, JS
Cortez, JS
Mansfield, LS
Rogers, AB
Fox, JG
Schauer, DB
机构
[1] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA
[2] Michigan State Univ, Infect Dis Unit, Dept Internal Med, E Lansing, MI 48824 USA
[3] Michigan State Univ, Natl Food Safety & Toxicol Ctr, E Lansing, MI 48824 USA
[4] MIT, Div Comparat Med, Cambridge, MA 02139 USA
[5] MIT, Biol Engn Div, Cambridge, MA 02139 USA
关键词
D O I
10.1128/IAI.72.5.2521-2527.2004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2521 / 2527
页数:7
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