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

• Published in: Infection and immunity Vol. 66; no. 5; pp. 1934 - 1940
• Main Authors: Whitehouse, Chris A., Balbo, Paul B., Pesci, Everett C., Cottle, Daniel L., Mirabito, Peter M., Pickett, Carol L.
• Format: Journal Article
• Language: English
• Published: 01.05.1998
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.66.5.1934-1940.1998

ABSTRACT 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 4 N 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.