Campylobacter jejuni Cytolethal Distending Toxin Causes a G(2)-Phase Cell Cycle Block

Cytolethal distending toxin (CDT) from the diarrheagenic bacterium Campylobacter jejuni was shown to cause a rapid and specific cell cycle arrest in HeLa and Caco-2 cells. Within 24 h of treatment, CDT caused HeLa cells to arrest with a 4N DNA content, indicative of cells in G(2) or early M phase. Immunofluorescence studies indicated that the arrested cells had not entered M phase, since no evidence of tubulin reorganization or chromatin condensation was visible. CDT treatment was also shown to cause HeLa cells to accumulate the inactive, tyrosine-phosphorylated form of CDC2. These results indicated that CDT treatment results in a failure to activate CDC2, which leads to cell cycle arrest in G(2). This mechanism of action is novel for a bacterial toxin and provides a model for the generation of diarrheal disease by C. jejuni and other diarrheagenic bacteria that produce CDT.