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.