CAMPYLOBACTER-JEJUNI CYTOLETHAL DISTENDING TOXIN CAUSES A G(2)-PHASE CELL-CYCLE BLOCK

Cytolethal distending toxin (CDT) from the diarrheagenic bacterium Cam pylobacter-jejuni was shown to cause a rapid and specific cell cycle a rrest in HeLa and Caco-2 cells, Within 24 h of treatment, CDT caused B eta cells to arrest with a 4N DNA content, indicative of cells in G(2) or early hi phase, Immunofluorescence studies indicated that the arre sted cells had not entered ICI phase, since no evidence of tubulin reo rganization or chromatin condensation was visible. CDT treatment was a lso shown to cause HeLa cells to accumulate the inactive, tyrosine-pho sphorylated form of CDC2. These results indicated that CDT treatment r esults in a failure to activate CDC2, which leads to cell cycle arrest in G,. This mechanism of action is novel for a bacterial toxin and pr ovides a model for the generation of diarrheal disease by C. jejuni an d other diarrheagenic bacteria that produce CDT.