The symptoms of diphtheria are caused by a toxin that is released by the bacteria that cause the condition.
Two types of bacteria can cause diphtheria and these include:
Infection with C. diptheriae occurs through inhalation of saliva droplets that contain the bacteria, while C. ulcerans can be picked up through contact with cattle that carry the bacteria in their nose and throat. Drinking unpasteurised milk or eating dairy goods made with unpasteurised milk can also lead to transmission of the infection.
Once infected, the bacteria quickly multiply within the body and spread through the inner lining of the throat, mouth and nose. The bacteria produce a toxin that kills cells in the throat. These cells then join to form the grey–white membrane that is typically seen in cases of diphtheria. The toxin can also spread via the bloodstream and cause damage to the nervous system and heart.
Not all diphtheria bacteria produce the diphtheria toxin. Only those that are infected with a bacteriophage can produce the toxin. The bacteriophage transfers the genetic material that codes for the toxin into the bacterial DNA.
The diphtheria toxin is a single polypeptide made up of fragment A and fragment B which are connected by a disulfide bond. Fragment B binds to the EGF-like domain of the heparin-binding EGF-like growth factor (HB-EGF) present on the surface of cells. This causes the cell to engulf the toxin inside an endosome, where it is divided into its two fragments.
The acidic environment of the endosome triggers fragment B to make holes in the membrane of the endosome. This allows fragment A to be released, which moves into the cell’s cytoplasm where it prevents the formation of new proteins by interrupting an essential step in protein synthesis.