Cytolethal Distending Toxin

Abstract

This chapter examines the molecular biology and biochemistry of cytolethal distending toxin (CDT) and its molecular mode of action. Transcript analysis of the Haemophilus ducreyi cdt gene cluster (Hd-cdtABC) indicated that the cdt genes are organized in an operon. The cdtABC operon encodes three CDT polypeptides, CdtA, CdtB, and CdtC. All three proteins bear apparent signal peptide coding sequences consistent with secretion across the inner membrane by the general export pathway. Biochemical evidence for the requirement of CdtA, CdtB, and CdtC in biological activity has recently been unequivocally demonstrated. Recent findings on the role of CdtB in the mechanism of CDT action, the similarity of CDT action to that of IR, the apparent pathway of CDT internalization, and the reconstitution of biological activity from pure CDT subunits constitute major advances in the understanding of CDT. The apparent cell type specificity for the induction of apoptosis versus cell cycle arrest and the activation of p53 following CDT treatment represent additional parallels between toxin action and radiation treatment. The resolution of this observation will yield not only important information regarding CDT but perhaps also the cellular response to DNA damage in general.