Campylobacter upsaliensis exerts a cytolethal distending toxin effect on HeLa cells and T lymphocytes

Campylobacter upsaliensis is an emerging human enteropathogen. However, lit tle is known about the pathogenesis of C. upsaliensis infection. In this st udy the authors demonstrate that C. upsaliensis whole-cell preparations and extracts produce a cytolethal distending toxin (CDT)-like effect on HeLa c ells characterized by progressive distension and nuclear fragmentation culm inating in cell death over 5 d. To further delineate the nature of this tox ic effect in relation to CDT from other pathogens, the effect of C. upsalie nsis on cellular events in epithelial cells and immunocytes was investigate d. C. upsaliensis lysate-treated HeLa cells subjected to FACScan analysis u sing carboxyfluorescein diacetete succinimidyl ester (CFDA-SE) as a cell tr acer demonstrated cell division arrest. Propidium iodide (PI) staining of H eLa cells revealed that cell cycle arrest occurred in G(2)/M. Human T lymph ocytes exposed to C. upsaliensis lysates also showed cell cycle arrest in G (2)/M. Using a combination of Annexin V/PI staining and TUNEL assay, cytodi stended HeLa cells were shown to undergo apoptotic cell death. These data p rovide the first insights into the virulence mechanisms of this novel enter opathogen.