title: Cytolethal distending toxins.
abstract: The cytolethal distending toxins (CDTs) constitute the most recently discovered family of bacterial protein toxins. CDTs are unique among bacterial toxins as they have the ability to induce DNA double strand breaks (DSBs) in both proliferating and nonproliferating cells, thereby causing irreversible cell cycle arrest or death of the target cells. CDTs are encoded by three linked genes ( cdtA, cdtB and cdtC) which have been identified among a variety of Gram-negative pathogenic bacteria. All three of these gene products are required to constitute the fully active holotoxin, and this is in agreement with the recently determined crystal structure of CDT. The CdtB component has functional homology with mammalian deoxyribonuclease I (DNase I). Mutation of the conserved sites necessary for this catalytic activity prevents the induction of DSBs as well as all subsequent intoxication responses of target cells. CDT is endocytosed via clathrin-coated pits and requires an intact Golgi complex to exert the cytotoxic activity. Several issues remain to be elucidated regarding CDT biology, such as the detailed function(s) of the CdtA and CdtC subunits, the identity of the cell surface receptor(s) for CDT, the final steps in the cellular internalization pathway, and a molecular understanding of how CDT interacts with DNA. Moreover, the role of CDTs in the pathogenesis of diseases still remains unclear.
authors.affiliation: Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden. Monica.Thelestam@mtc.ki.se
authors.forename: M
authors.initials: M
authors.lastname: Thelestam
authors.forename: T
authors.initials: T
authors.lastname: Frisan
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000503:physiopathology; D001427:Bacterial Toxins / Q000737:chemistry / Q000494:pharmacology*; D008322:Mammals
chemical_list: D001427:Bacterial Toxins; C067044:cytolethal distending toxin