Corynebacterium diphtheriae is a Gram-positive bacterium which infects epithelial cells of the upper respiratory tract and produces diphtheria toxin

Diphtheria toxin is proteolytically cleaved, forming a two part toxin that is held together by a disulfide bridge. The amino-terminal carries the toxin's enzymatic activity, capable of ADP-ribosylation and inactivation of translation elongation factor 2 (EF-2). The carboxy-terminal domain binds to specific host receptors, the heparin-binding EGF-like growth factor (HB-EGF) on human epithelial cells, and translocates the catalytic domain into the cell. After binding to the cell receptor, the toxin is taken up by endocytosis. The pH of the endocytic vesicle then drops and the translocation region of the toxin helps guide the catalytic domain into the host cytoplasm where it is released. Within the cytoplasm, diphtheria toxin catalyzes the ADP-ribosylation of eukaryotic aminoacyl-transferase II (EF-2) using NAD as a substate. This reaction forms the basis for its toxicity toward eukaryotic organisms. Diphtheria toxin is highly potent and as little as one catalytic domain is thought to cause cell death. In cell culture, diphtheria toxin inhibits protein synthesis and causes death in cells carrying the HB-EGF receptor. This toxin has been used to specifically eliminate receptor-expressing cells in transgenic mice.