Microbe profile: Corynebacterium diphtheriae - an old foe always ready to seize opportunity

Diphtheria AB toxin mode of action. The diphtheria AB exotoxin consists of two polypeptide chains - A and B which are linked by a disulfide bridge. The B chain binds to the heparin-binding epidermal growth factor precursor on eukaryotic cells and is endocytosed. Acidification of the endosome results in a conformational change to the A and B chains and breaking of the disulphide bridge. The B chain remains in the endosome, but the A chain is translocated to the cytoplasm where it ADP-ribosylates host eEF-2, blocking protein synthesis which leads to cell death. Corynebacterium diphtheriae is a globally important Gram-positive aerobic Actinobacterium capable of causing the toxin-mediated disease, diphtheria. Diphtheria was a major cause of childhood mortality prior to the introduction of the toxoid vaccine, yet it is capable of rapid resurgence following the breakdown of healthcare provision, vaccination or displacement of people. The mechanism and treatment of toxin-mediated disease is well understood, however there are key gaps in our knowledge on the basic biology of C. diphtheriae particularly relating to host colonisation, the nature of asymptomatic carriage, population genomics and host adaptation.