Diphtheria toxin (Corynebacterium diphtheriae)

Abstract Diphtheria toxin is the primary virulence factor of toxigenic C. diphtheriae the etiologic agent of clinical diphtheria (Pappenheimer 1977). The structural gene for diphtheria toxin, tox, is carried by a closely related family of corynebacteriophages of which the β-phage has been the best studied (Buck et al. 1985; Bishai and Murphy 1988). The regulation of tox gene expression is controlled by the C. diphtheriae determined iron-activated repressor DtxR (Tao et al. 1994). Diphtheria toxin is produced in maximal yield only during the decline phase of the bacterial growth cycle when iron becomes the growth rate limiting substrate. The toxin is synthesized in precursor form and is co-translationally secreted into the growth medium (Smith et al. 1980). As shown in Fig. 1, diphtheria toxin is a three domain protein and is composed of the catalytic (C), transmembrane (T), and receptor binding (R) domains. The R domain has been shown to specially bind to a heparin binding epidermal growth factor-like precursor on the surface of sensitive eukaryotic cells (Naglich et al. 1992).