Cytolethal distending toxin (CDT): a bacterial weapon to control host cellproliferation?

Cytolethal distending toxins (CDT) constitute a family of genetically relat ed bacterial protein toxins able to stop the proliferation of numerous cell lines. This effect is due to their ability to trigger in target cells a si gnaling pathway that normally prevents the transition between the G2 and th e M phase of the cell cycle. Produced by several unrelated Gram-negative mu cosa-associated bacterial species. CDTs are determined by a cluster of thre e adjacent genes (cdtA, cdtB, cdtC) encoding proteins whose respective role is not yet fully elucidated. The CDT-B protein presents sequence homology to several mammalian and bacterial phosphodiesterases, such as DNase 1. The putative nuclease activity of CDT-B. together with the activation by CDT o f a G2 cell cycle checkpoint, strongly suggests that CDT induces art as yet uncharacterized DNA alteration. However, the effective entry of CDT into c ells and subsequent translocation into the nucleus have not yet been demons trated by direct methods. The relationship between the potential DNA-damagi ng properties of this original family of toxins and their role as putative virulence factors is discussed. (C) 2001 Federation of European Microbiolog ical Societies. Published by Elsevier Science B.V. All rights reserved.