Table 1.

Comparative key characteristics of CDT, typhoid toxin, and colibactin

Features	CDT and Typhoid Toxin	Colibactin	References
Type of DNA damage	Single-strand break, double-strand break, chromosomal instability (chronic exposure)	DNA cross-link?, double-strand break chromosomal instability	51, 81, 84, 85, 94, 110, 112, 122
Cell cycle arrest	G2 phase (G1 phase)	G1 phase, G2 phase, S phase	23, 90, 110, 111
Secretion	Yes (present in supernatant)	No (contact dependent)	11, 49, 110
Distribution	Pathogenic E. coli, Shigella E. albertii P. alcalifaciens Salmonella Typhi and iNTS	E. coli of phylogroup B2 (ExPEC, commensal) Citrobacter, Klebsiella, Enterobacter	17, 27, 89, 110, 137, 138, 140
Senescence	Yes, SASP	Yes, SASP	88, 94, 113
Nature	Heterotrimeric complex type AB2 (CdtA, CdtB, CdtC) or heptameric complex type A2B5 (CdtB, PltA, PltB5)	Nonribosomal peptide-polyketide hybrid compound(s)	29, 110, 130
Genes	3 genes (cdtA, cdtB, and cdtC) clustered in operon or in Salmonella, cdtB localized in CdtB islet with pltA and pltB	19 genes hosted on the pks genomic island	26, 27, 29, 110
Enzymatic activity	DNase (PIP3 phosphatase?)	DNA intercalation and alkylation?	51, 97, 122
Trafficking	Endocytosis, anterograde transport	?	58, 76, 80
Receptor	Lipid raft, carbohydrates?	?	53, 54, 76
Bacterial DNA protection	Secretion, autoinhibition with N terminus of CdtC occluding CdtB active site?	Defense protein ClbS, maturation of colibactin in the periplasm	51, 52, 129, 131
Prodrug	No	Yes, precolibactin is cleaved by ClbP	127, 128, 129
Homology	DNase I	Duocarmycin, acylfulvenes?	51, 133
Procarcinogen	No evidence in Enterobacteriaceae	Yes (in inflammatory context)	114, 116