Question
Diphtheria toxin
Answer
Diphtheria toxin is an AB-type exotoxin produced by strains of Corynebacterium diphtheriae that are lysogenized by a bacteriophage carrying the tox gene — only such lysogenized (phage-converted) strains are toxigenic; non-lysogenized strains do not produce toxin and cause, at most, mild local disease.
Structure and mechanism:
- The B (binding) subunit binds a specific host cell surface receptor (heparin-binding EGF-like growth factor precursor), mediating entry of the toxin into the cell by receptor-mediated endocytosis.
- The A (active) subunit, once inside the cell, ADP-ribosylates Elongation Factor-2 (EF-2) — a protein essential for translocation of the ribosome along mRNA during protein synthesis — using NAD+ as the ADP-ribose donor. This inactivates EF-2, halting host cell protein synthesis entirely and leading to cell death. A single molecule of toxin is sufficient to kill a cell, reflecting its extreme potency.
Tissue tropism: the toxin has particular affinity for tissues with high protein turnover — notably cardiac muscle (causing myocarditis, the most serious complication, often fatal) and peripheral nerves/Schwann cells (causing demyelination, e.g., palatal palsy, later limb paralysis) — accounting for the classical systemic complications of diphtheria, which occur despite the infection itself remaining localized to the pharynx/skin.
Clinical/laboratory relevance: toxin production is confirmed in the laboratory by Elek’s gel precipitation test; the toxin can be inactivated by formalin treatment while retaining immunogenicity, producing diphtheria toxoid, the basis of the DPT vaccine; diphtheria antitoxin neutralizes only free (not cell-bound) toxin, so must be given promptly on clinical suspicion, before all toxin has bound to target tissue.