Cytolethal distending toxin generates cell death by inducing a bottleneck in the cell cycle

Cytolethal distending toxin (CDT) is a bacterial protein that is widely distributed among Gram-negative bacteria including Escherichia coli, Campylobacter spp., enterohepatic Helicobacter spp., Actinobacillus actinomycetemcomitans and Haemophilus ducreyi. In vitro studies demonstrated that it is able to stop proliferation of various cell lines. The toxin is composed of three subunits designated CDTs A, B and C. The B subunit targets the eukaryotic DNA and triggers a signalling pathway involving different protein kinases which results in a cell block before entering into mitosis. To date, the individual role of the A and C subunits has not been totally elucidated. There are indications that the CDT is also produced in vivo. Its exact role in pathogenesis is not yet clear, but possible actions include inhibition of epithelial cell proliferation, apoptosis of immune cells and inhibition of a fibrotic response.