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Infection and Immunity, September 2001, p. 5752-5759, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5752-5759.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cytolethal Distending Toxin Demonstrates Genotoxic Activity in a Yeast Model

Duane C. Hassane,1 Robert B. Lee,1 Michael D. Mendenhall,2 and Carol L. Pickett1,*

Department of Microbiology and Immunology1 and Department of Biochemistry and L. P. Markey Cancer Center,2 College of Medicine, University of Kentucky, Lexington, Kentucky 40536

Received 2 February 2001/Returned for modification 28 March 2001/Accepted 12 June 2001

Cytolethal distending toxins (CDTs) are multisubunit proteins produced by a variety of bacterial pathogens that cause enlargement, cell cycle arrest, and apoptosis in mammalian cells. While their function remains uncertain, recent studies suggest that they can act as intracellular DNases in mammalian cells. Here we establish a novel yeast model for understanding CDT-associated disease. Expression of the CdtB subunit in yeast causes a G2/M arrest, as seen in mammalian cells. CdtB toxicity is not circumvented in yeast genetically altered to lack DNA damage checkpoint control or that constitutively promote cell cycle progression via mutant Cdk1, because CdtB causes a permanent type of damage that results in loss of viability. Finally, we establish that CDTs are likely to be potent genotoxins, as indicated by in vivo degradation of chromosomal DNA associated with expression of CdtB---suggesting that the varied distribution of CDT in bacteria implicates many human pathogens as possessors of genotoxic activity.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Medicine, University of Kentucky, 800 Rose St., Lexington, KY 40536. Phone: (859) 323-5313. Fax: (859) 257-8994. E-mail: cpicket{at}pop.uky.edu.

Infection and Immunity, September 2001, p. 5752-5759, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5752-5759.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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