1.C.98 The Cytolethal Distending Toxin (CDT) Family Cytolethal distending toxins (CDTs) are tripartite protein exotoxins produced by a diverse group of pathogenic Gram-negative bacteria. Based on their ability to induce DNA damage, cell cycle arrest, and apoptosis of cultured cells, CDTs are proposed to enhance virulence by blocking cellular division and/or directly killing epithelial and immune cells. CdtA and C may deliver CdtB with the animal host cell cytoplasm where it acts as a DNase. This activity is required for toxicity (Thelestam and Frisan, 2004). Eshraghi et al. (2010) demonstrated that CDTs from Haemophilus ducreyi, Aggregatibacter actinomycetemcomitans, Escherichia coli, and Campylobacter jejuni differ in their abilities to intoxicate host cells with defined defects in host factors previously implicated in CDT binding, including glycoproteins, and glycosphingolipids. The absence of cell surface sialic acid sensitized cells to intoxication by three of the four CDTs tested. Surprisingly, fucosylated N-linked glycans and glycolipids, previously implicated in CDT-host interactions, were not required for intoxication by any of the CDTs tested. Finally, altering host-cellular cholesterol, also previously implicated in CDT binding, affected intoxication by only a subset of CDTs tested (Eshraghi et al., 2010). Haemophilus CdtA and CdtC are found in species of Escherichia, Shigella, Haemophilus and Aggregatibacter (γ-proteobacteria) as well as Campylobacter and Helicobacter (ε-proteobacteria). CdtB, the endo/exo-nuclease/phosphatase component, is found in these organisms plus other Gram-negative bacteria.
References:
Magyar, L.B., E. Ábrahám, Z. Lipinszki, R.L. Tarnopol, N.K. Whiteman, V. Varga, D. Hultmark, I. Andó, and G. Cinege. (2025). Pore-Forming Toxin-Like Proteins in the Anti-Parasitoid Immune Response of Drosophila. J Innate Immun 17: 10-28.
Smith, J.L. and D.O. Bayles. (2006). The contribution of cytolethal distending toxin to bacterial pathogenesis. Crit. Rev. Microbiol. 32: 227-248.
Varon, C., I. Mocan, B. Mihi, C. Péré-Védrenne, A. Aboubacar, C. Moraté, M. Oleastro, F. Doignon, D. Laharie, F. Mégraud, and A. Ménard. (2014). Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells. J Infect Dis 209: 588-599.
Examples:
TC#	Name	Organismal Type	Example
1.C.98.1.1	The heterotrimeric CDT, CdtA/B/C toxin complex. CdtA and CdtC may form a heterodimeric complex required for CdtB delivery. Localized to the cell outer membrane. Contains a ricin B-type lectin domain (Smith and Bayles 2006). All three have an N-terminal TMS, and possibly a second one near their C-termini.	Gram-negative Bacteria	Trimeric CdtA/B/C of E. coli CdtA(Q46668) CdtB(Q46669) CdtC(Q46670)

1.C.98.1.2	Cytolethal distending pore-forming toxin B (CdtB) of 317 aas and 2 TMSs of Drosophila primaeva (Magyar et al.* 2025).*		CdtB of Drosophila primaeva

1.C.98.1.3	Helicobacter pullorum cytolethal distending toxin, CdtB, of 274 aas, targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells (Varon et al. 2014). CdtB also induced an atypical delocalization of vinculin from focal adhesions to the perinuclear region, formation of cortical actin-rich large lamellipodia with an upregulation of cortactin, and decreased cellular adherence. In conclusion, the CDT of H. pullorum is responsible for major cytopathogenic effects in vitro, confirming its role as a main virulence factor of this emerging human pathogen.		CdtB of Helicobacter pullorum