Cytolethal distending toxin sequence and activity in the enterohepatic pathogen Helicobacter hepaticus

Little is known about the molecular pathogenesis of hepatitis and enterocul itis caused by enterohepatic Helicobacter species. Sonicates of the murine pathogen Helicobacter hepaticus were found to cause progressive cell disten sion, accumulation of filamentous actin, and G(2)/M cell cycle arrest in He La 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 l aboratory strain of Escherichia coli carrying the cloned cdtABC gene cluste r from H. hepaticus reproduced the cytotoxic activities seen with sonicates of H. hepaticus. Cytolethal distending toxin activity is a potential virul ence determinant of H. hepaticus that may play a role in the pathogenesis o f Helicobacter-associated hepatitis and enterocolitis.