In vitro and in vivo characterization of Helicobacter hepaticus cytolethal distending toxin mutants.
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.
Young
Vincent B
VB
Department of Microbiology and Molecular Genetics, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA. youngvi@msu.edu
Knox
Kimberly A
KA
Pratt
Jason S
JS
Cortez
Jennifer S
JS
Mansfield
Linda S
LS
Rogers
Arlin B
AB
Fox
James G
JG
Schauer
David B
DB
D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics* / Q000633:toxicity; D003092:Colitis / Q000209:etiology / Q000473:pathology; D005260:Female; D005798:Genes, Bacterial; D006367:HeLa Cells; D016481:Helicobacter Infections / Q000209:etiology / Q000473:pathology; D044923:Helicobacter hepaticus / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D009154:Mutation
D001427:Bacterial Toxins; C067044:cytolethal distending toxin; D016753:Interleukin-10