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Infect Immun, May 1998, p. 1934-1940, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Campylobacter jejuni Cytolethal Distending Toxin Causes a G2-Phase Cell Cycle Block

Chris A. Whitehouse,1 Paul B. Balbo,1 Everett C. Pesci,1,dagger Daniel L. Cottle,1 Peter M. Mirabito,2 and Carol L. Pickett1,*

Department of Microbiology and Immunology, College of Medicine, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0084,1 and School of Biological Sciences, University of Kentucky, Lexington, Kentucky 40506-02252

Received 13 October 1997/Returned for modification 18 November 1997/Accepted 12 February 1998

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Chandler Medical Center, 800 Rose St., University of Kentucky, Lexington, KY 40536-0084. Phone: (606) 323-5313. Fax: (606) 257-8994. E-mail: cpicket{at}pop.uky.edu.

dagger Present address: Department of Microbiology and Immunology, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642.

Infect Immun, May 1998, p. 1934-1940, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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