Mechanisms utilized by Cytolethal Distending Toxins to perturb host cell function and vitality

The cytolethal distending toxins (Cdts) were first described as a heat labile factor from Escherichia coli and Campylobacter spp cultures and shown to be capable of causing cellular distention. More recent studies demonstrate that Cdts are derived from a more diverse group of Gram-negative pathogens including: Aggregatibactor actinomycetemcomitans, Haemophilus ducreyi, Helicobacter hepaticus and Shigella dysenteria, among others. It is now clear that Cdts represent a family of toxins that are capable of causing cell cycle arrest and apoptosis in a number of cell lines and cell types including lymphocytes, epithelial cells and fibroblasts among others. Furthermore, other cell types, such as mast cells and macrophages exhibit resistance to Cdt-induced cell death although these cells are susceptible to toxin-mediated alterations in cell function. The Cdt holotoxin is a heterotrimeric complex that functions as an AB2 toxin; moreover, recent advances have greatly contributed to our understanding of Cdt structure, functional role of each subunit and the molecular mechanisms involved in internalization, the ability of toxin subunits to interact and hijack signaling cascades that ultimately lead to cell cycle arrest, apoptosis and other alterations in cell function. The specific role that Cdts might play in disease associated with Cdt-producing pathogens is not clear, but there is evidence to suggest multiple possibilities including: alterations in acquired immunity, inappropriate activation of innate immunity leading to chronic inflammation, destruction of epithelial barriers and contribution to genomic instability possibly leading to tumor progression.

The aim of this Research Topic is to highlight and cover recent understanding of Cdt subunit structure and function and the molecular mechanism by which the toxin acts to contribute to the pathogenesis of disease. Contributions to this Topic will advance our understanding of the diverse functions that are either shared or unique to the diverse group of Cdts. It is anticipated that chapters will consist of research articles, reviews and opinions that collectively will help to clarify the role of Cdt in host-parasite interactions and the pathogenesis of disease.