Corynebacterium diphtheriae is the pathogenic bacterium that causes diphtheria. It is also known as the Klebs–Löffler bacillus, because it was discovered in 1884 by German bacteriologists Edwin Klebs (1834–1912) and Friedrich Löffler (1852–1915). The bacteria are usually harmless unless they are infected by a bacteriophage that carries a gene that gives rise to a toxin. This toxin causes the disease. Diphtheria is caused by the adhesion and infiltration of the bacteria into the mucosal layers of the body, primarily affecting the respiratory tract and the subsequent release of an endotoxin. The toxin has a localized effect on skin lesions, as well as a metastatic, proteolytic effects on other organ systems in severe infections. Originally a major cause of childhood mortality, diphtheria has been almost entirely eradicated due to the vigorous administration of the diphtheria vaccination in the 1910s. Diphtheria is no longer transmitted as frequently due to the development of the vaccine, DTaP. Although diphtheria outbreaks continue to occur, this often in developing countries where the majority of the population is not vaccinated. Classification Four subspecies are recognized: C. d. mitis, C. d. intermedius, C. d. gravis, and C. d. belfanti. The four subspecies differ slightly in their colonial morphology and biochemical properties, such as the ability to metabolize certain nutrients. All may be toxigenic (and therefore cause diphtheria) or not toxigenic. Strain subtyping involves comparing species of bacteria and categorizing them into subspecies. Strain subtyping also helps with identifying the origin of a certain bacteria's outbreak. However, when it comes to the subtyping of C. diphtheriae, there is not a lot of useful or accurate classification due to the lack of publicly available resources to identify strains and therefore finding the origin of outbreaks. Toxin C. diphtheriae produces diphtheria toxin which alters protein function in the host by inactivating the elongation factor EF-2. This causes pharyngitis and 'pseudomembrane' in the throat. The strains which are toxigenic are ones which have been infected with a bacteriophage. The diphtheria toxin gene is encoded by the bacteriophage found in toxigenic strains, integrated into the bacterial chromosome. The diphtheria toxin repressor is mainly controlled by iron. It serves as the essential cofactor for the activation of target DNA binding. A low concentration of iron is required in the medium for toxin production. At high iron concentrations, iron molecules bind to an aporepressor on the beta bacteriophage, which carries the Tox gene. When bound