Diphtheria toxin (DT) is one of the most extensively studied bacterial toxins, due to the fact that the causative organism was one of the first bacteria isolated and grown in pure culture, and the toxin among the first toxins discovered (3). Diphtheria exotoxin is a 62kDa polypeptide composed of a B subunit which binds to cell receptors at clathrin-coated pit sites of endosome, followed by release of the active A subunit. The A subunit is released by proteolytic cleavage of a peptide bond with reduction of a disulfide bridge, followed by a conformational change in the B subunit in the acidic pH of the endosome, allowing release of the A subunit into the cytoplasm. The A subunit inactivates elongation factor-2 (EF-2) via ADP-ribosylation, thus acting as a polypeptide chain terminator of host cell protein synthesis. The cell is then unable to repair its own membranes, and cytotoxicity results. The toxin is very potent: a single molecule is enough to inactivate all of the EF-2 in a cell and halt protein synthesis within a few hours. The estimated human lethal dose of DT is 0.1 mg/kg.

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