The cytolethal distending toxins induce DNA damage and cell cycle arrest

The cytolethal distending toxins (CDTs) are a newly discovered family of ba cterial protein toxins with the unique ability to interfere with the cell c ycle, causing irreversible cell cycle arrest and consequently death of the target cells. CDTs are encoded by three linked genes (cdtA, cdtB and cdtC) and are produced by a variety of Gram negative bacteria. The mechanism of a ction of this toxin family only now begins to be elucidated. CDTs are inter nalized by endocytosis and require an intact Golgi complex to exert their c ytotoxic activity. The CdtB component was shown to have functional homology with the mammalian deoxyribonuclease I (DNase I) and the induction of cell cycle-arrest in mammalian cells mimicked that induced by DNA damaging agen ts, suggesting that DNA is the cellular target. Still there are many issues that need to be clarified, such as identification of the function(s) of Cd tA and CdtC, characterization of the receptor(s), understanding of the fina l steps of the internalization pathway and localization of the active compo nent. This review focuses mainly on the effect of CDTs on mammalian cells, highlighting the questions that remain to be answered regarding their molec ular mode of action. (C) 2001 Elsevier Science Ltd. All rights reserved.