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Infection and Immunity, January 2000, p. 184-191, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Cytolethal Distending Toxin Sequence and Activity in the Enterohepatic Pathogen Helicobacter hepaticus

Vincent B. Young,1,2 Kimberly A. Knox,3 and David B. Schauer1,3,*

Division of Bioengineering and Environmental Health1 and Division of Comparative Medicine,3 Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and Infectious Diseases Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 021142

Received 27 July 1999/Returned for modification 10 September 1999/Accepted 14 October 1999

Little is known about the molecular pathogenesis of hepatitis and enterocolitis caused by enterohepatic Helicobacter species. Sonicates of the murine pathogen Helicobacter hepaticus were found to cause progressive cell distension, accumulation of filamentous actin, and G2/M cell cycle arrest in HeLa cell monolayers. The genes encoding this cytotoxic activity were cloned from H. hepaticus. Three open reading frames with closest homology to cdtA, cdtB, and cdtC from Campylobacter jejuni were identified. Sonicates of a laboratory strain of Escherichia coli carrying the cloned cdtABC gene cluster from H. hepaticus reproduced the cytotoxic activities seen with sonicates of H. hepaticus. Cytolethal distending toxin activity is a potential virulence determinant of H. hepaticus that may play a role in the pathogenesis of Helicobacter-associated hepatitis and enterocolitis.

* Corresponding author. Mailing address: MIT, Rm. 56-787, Cambridge, MA 02139. Phone: (617) 253-8113. Fax: (617) 258-0225. E-mail: schauer{at}mit.edu.

Infection and Immunity, January 2000, p. 184-191, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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