Diphtheria Toxin and Cytosolic Translocation Factors

Diphtheria Toxin (DT) was the first investigated bacterial protein toxin. As one of the most extensively studied bacterial protein toxins, it has served as a model system for the analysis of other protein toxins (Pappenheimer, 1977). As reviewed by Pappenheimer, Loeffler identified Corynebacterium diphtheriae as the causative agent of diphtheria in 1884, and the toxin was first described in the culture medium of C. diphtheriae by Roux and Yersin in 1888. The gene for DT is encoded by a family of closely related corynebacteriophages (Uchida et al., 1971; Greenfield et al., 1983), and is expressed only under conditions of iron deprivation (Pappenheimer, 1977). Regulation of DT expression is under control of the iron-activated diphtheria toxin repressor, DTxR, which is encoded in the C. diphtheriae genome and inhibits transcription of DT in the presence of iron and other transition metal ions (Love and Murphy, 2000).