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

doi:10.1128/IAI.68.1.184-191.2000

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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 foundto cause progressive cell distension, accumulation of filamentousactin, and G₂/M cell cycle arrest in HeLa cell monolayers. Thegenes 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. Sonicatesof a laboratory strain of Escherichia coli carrying the clonedcdtABC gene cluster from H. hepaticus reproduced the cytotoxicactivities seen with sonicates of H. hepaticus. Cytolethal distendingtoxin activity is a potential virulence determinant of H. hepaticusthat may play a role in the pathogenesis of Helicobacter-associatedhepatitis andenterocolitis.

^* 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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