Campylobacter jejuni cytolethal distending toxin causes a G2-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 G2 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 G2. 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.
Whitehouse
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CA
Department of Microbiology and Immunology, College of Medicine, Chandler Medical Center, University of Kentucky, Lexington 40536-0084, USA.
Balbo
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PB
Pesci
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EC
Cottle
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DL
Mirabito
P M
PM
Pickett
C L
CL
D001427:Bacterial Toxins / Q000633:toxicity*; D016203:CDC2 Protein Kinase / Q000502:physiology; D018938:Caco-2 Cells; D002110:Caffeine / Q000494:pharmacology; D016123:Campylobacter jejuni / Q000472:pathogenicity*; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans
D001427:Bacterial Toxins; C067044:cytolethal distending toxin; D002110:Caffeine; D016203:CDC2 Protein Kinase