%0 Journal Article
%T Cytolethal Distending Toxin: A Unique Variation on the AB Toxin Paradigm
%A Joseph M. DiRienzo
%J New Journal of Science
%D 2014
%R 10.1155/2014/249056
%X Some of the most potent toxins produced by plants and bacteria are members of a large family known as the AB toxins. AB toxins are generally characterized by a heterogenous complex consisting of two protein chains arranged in various monomeric or polymeric configurations. The newest class within this superfamily is the cytolethal distending toxin (Cdt). The Cdt is represented by a subfamily of toxins produced by a group of taxonomically distinct Gram negative bacteria. Members of this subfamily have a related AB-type chain or subunit configuration and properties distinctive to the AB paradigm. In this review, the unique structural and cytotoxic properties of the Cdt subfamily, target cell specificities, intoxication pathway, modes of action, and relationship to the AB toxin superfamily are compared and contrasted. 1. Introduction Bacteria secrete a myriad of different types of proteins that exhibit a cell damaging or ¡°cytotoxic¡± activity. Examples include but are not limited to membrane-damaging proteins such as RTX (repeats in toxin) and CDC (cholesterol-dependent cytolysins), cell surface interacting proteins such as ST (heat-stable enterotoxins), and superantigens, as well as other proteins that attack cytosolic activities. One of the recurring organizational themes among secreted bacterial protein toxins that target intracellular processes in mammalian cells is a complex composed of at least two heterogeneous polypeptide chains or subunits. Each chain makes a distinct contribution to cell intoxication or toxic activity. The superfamily of cytotoxins that exhibit this structural arrangement have been generally labeled as the AB toxins [1]. In this arrangement, the A chain or subunit typically functions as an enzyme that disrupts a specific cell process or pathway and the B chain or subunit, in monomeric or polymeric form, and promotes binding of the holotoxin to the target cell surface. The newest member of the AB toxin superfamily, discovered by Johnson and Lior in 1987 [2], is the cytolethal distending toxin (Cdt). This toxin was named so because Chinese hamster ovary (CHO) cells became stretched or enlarged when exposed to cell-free filtrates of enteropathogenic Escherichia coli (EPEC) isolated from young children diagnosed with gastroenteritis. Nucleotide sequences of the E. coli cdt genes were first reported in 1994 by Pickett et al. [3] and Scott and Kaper [4] and revealed that the toxin was composed of three heterogenous subunits (CdtA, CdtB, and CdtC). Publication of this sequence led to the rapid discovery of a family that represents a
%U http://www.hindawi.com/journals/njos/2014/249056/