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• W3023822022 endingPage "602" @default.
• W3023822022 startingPage "558" @default.
• W3023822022 abstract "Bacterial genotoxins are unique among bacterial toxins because their molecular target is DNA. The consequence of intoxication is the induction of DNA breaks that, if not properly repaired, results in irreversible cell cycle arrest (senescence) or death in the target cells. At present, only three bacterial genotoxins have been identified. Two are protein toxins: the cytolethal distending toxin (CDT) family produced by a number of Gram-negative bacteria and the typhoid toxin produced by Salmonella enterica serovar Typhi. The third member, colibactin, is a peptide-polyketide genotoxin, produced by strains belonging to the phylogenetic group B2 of Escherichia coli. The crystal structure is available for the two protein toxins and demonstrates that while CDT is an AB2 toxin, the typhoid toxin is an A2B5 toxin. However, the two toxins share a common feature: the presence of the CdtB active “A” subunit, which is structurally and functionally homologous to the mammalian DNase I. The two accessory “B” subunits of CDT are encoded by the cdtA and cdtC genes and are required for binding and internalization of the active subunit into the target cell. CDT is internalized by dynamin-dependent endocytosis and retrogradely transported via the Golgi complex to the endoplasmic reticulum, and further to the nucleus, where it exerts the cytotoxic activity. This chapter focuses on the members of the CDT family, which are protein toxins. Specifically, it will review and discuss the features of the toxins’ structure and mode of action, the consequence of intoxication for the target cells, the distribution among bacteria, the possible role of the toxin in bacterial pathogenesis, and the possible application of CDT in drug development. Further, it highlights the questions that are still open in the exciting field of bacterial genotoxins. Given the interesting mode of action of these effectors, I will briefly summarize the relevant literature on the non-protein toxin colibactin." @default.
• W3023822022 created "2020-05-13" @default.
• W3023822022 creator A5088922536 @default.
• W3023822022 date "2015-01-01" @default.
• W3023822022 modified "2023-10-04" @default.
• W3023822022 title "Bacterial genotoxins" @default.
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