Cytolethal Distending Toxin Sequence and Activity in the Enterohepatic PathogenHelicobacter hepaticus

Abstract

Little is known about the molecular pathogenesis of hepatitis and enterocolitis caused by enterohepatic Helicobacter species. Sonicates of the murine pathogen Helicobacter hepaticuswere 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 fromH. hepaticus. Three open reading frames with closest homology to cdtA, cdtB, and cdtCfrom Campylobacter jejuni were identified. Sonicates of a laboratory strain of Escherichia coli carrying the clonedcdtABC gene cluster from H. hepaticusreproduced 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.