Characterization of host-pathogen interaction of two bacterial toxins: Anthrax edema toxin and Escherichia coli cytolethal distending toxin

Pathogenic and symbiotic bacteria have developed mechanisms that promote survival and propagation within the host. In the case of symbiotic bacteria, the mechanisms developed are generally not harmful to the host. Pathogenic bacteria, however, have developed mechanisms that cause damage to the host thereby contributing to disease. These mechanisms include a broad range of virulence factors involved in such tasks as bacterial invasion, adhesion, internalization (in the case of intracellular pathogens), modulation of host cell functions, resisting/counteracting host immune defenses, and in some cases, activation of the immune system. In many instances, these virulence factors mimic host cell molecules and allow pathogens to hijack or modulate cellular functions. The expression of multiple virulence factors allow pathogens to exploit host cell functions and subvert host immune defenses for the ultimate survival of the bacteria. A full understanding on the mode of entry, action and effect on target host cells is required to fully comprehend disease progression triggered by a particular pathogen, as well as to provide better insight into disease treatment. In this work I present characterization of toxins produced by Bacillus anihracis and a family of toxins, termed cytolethal distending toxin (CDT), produced by various Gram negative bacteria. Chapters 2-4 present work addressing the mode of action and modulation of host cell response by edema toxin produced by B. anthraces. Chapter 5 presents work dealing with the host cell factors required for binding and entry of CDT produced by Escherichia coli (EcCDT).