Pathogenicity of diphtheria
The pathogenesis of diphtheria bacilli occurs in the nasopharynx.
Carynobacterium diphtheriae releases a toxin that prevents cellular protein
synthesis. The toxin causes tissue destruction and membrane formation. The
diphtheria toxin is an exotoxin. The toxin gene is normally encoded by a
bacteriophage, a virus which infects bacteria. The toxin gains entry into the
human cell cytoplasm and then inhibits protein synthesis. (Mardigo and
Martinko, 2006)The toxin is absorbed into the bloodstream and creates a
pseudomembrane at the back of the throat. The pseudomembrane is a fibrin
network that is infected with many corynebacterium diphtheriae cells that are
multiplying over a necrotic lesion on the epithelial cells found on the back of
the throat. (Mardigo and Martinko, 2006) The toxins found in the bacterium
are not encoded in the bacterial chromosome but encoded by a lysogenic
phage infecting all toxigenic strains. The diphtheria toxin is a single polypeptide
chain containing 535 amino acids linked by two disulphide bridges. (Lee and
Iglewski, 1984)
(Collier, 1975)
The diphtheria toxin is made up of two fragments; fragment A and fragment B.
Fragment B helps the toxin enter the host cell, whereas fragment A prevents
protein synthesis. (Collier, 1975) Fragment B is a recognition subunit which
binds to the EGF-like domain of heparin-binding EGF-like growth factor, (HB-
EGF). The binding of the HB-EGF receptor on the hosts’ plasma membrane
results in the activation of receptor-mediated endocytosis, in which the cell
absorbs the toxin with an endosome. When the toxin enters the endosome it is
separated into individual A and B fragments by a trypsin-like protease. (Collier,
1975) Due to the acidity of the endosome fragment B creates pores in the
endosome membrane; these events catalyse the discharge of fragment A into
the cell cytoplasm. Fragment A prevents protein synthesis by catalysing ADPribosylaton of elongation factor-2 (EF-2). EF-2 is a protein that is extremely
vital in the translation step of protein synthesis. In ADP-Ribosylation ADPribose is transported from NAD+ to a diphthamide residue found in the EF-2
protein. During protein translation EF-2 is required for the transfer of tRNA
from the A-site to the P-site of the ribosome; however the ADP-Ribosylation of
the EF-2 protein results in the inhibition of protein formation. (Lee and
Iglewski, 1984)
The catalytic C domain of the toxin found in fragment A is responsible for the
transfer of ADP ribose. The T domain unfolds in the membrane by a pH
induced conformational change resulting in its entrance into the endosomal
membrane. (Todar, 2011)
The R domain found in fragment B permits the toxin to enter the hosts’ cell by
binding to the cell surface receptor. (Todar, 2011)
When the toxin is produced at the site of the membrane it is then absorbed by
the bloodstream and transferred through the tissues of the body. The toxin is
responsible for the majority of complications regarding myocarditis and
neuritis. The toxins can result in the decrease of platelets (thrombocytopenia)
and protein in the urine (proteinuria). (Nemours, 1995) Once the host is
infected the pathogenic bacterium multiplies and spreads quickly via the inside
surface of the mouth, nose and throat. The toxin kills the cells in the throat
behaving like a poison. This results in the grey-white membrane in the throat,
which are dead throat cells. In worse cases the toxin may spread through the
blood and destroy the heart and nervous system. (Nemours, 1995)
(Nemours, 1995)
Referencing

Mardigan, F. and Martinko, D., (2006). Diphtheria and Cholera Toxins. Journal of
Biology, [e-journal] 28(11), 89-96 Available through: SciVerse Science Direct
[Accessed: 20th October 2011]

Nemours, L., (1995) Diphtheria Bacterium Toxin. The British Journal of Clinical
Chemistry, [e-journal] 23(2), 12-16 Available through: SciVerse Science Direct
[Accessed: 20th October 2011]

Todar. K., (2011). Diphtheria. Journal of bacteriology, [e-journal] 124(19), 57-69
Available through: Medscape [Accessed: 20th October 2011]

Collier, J. R., (1975).Diphtheria toxin: mode of action and structure. Journal of
bacteriology and molecular biology, [e-journal] 39(1), 54-85 Available through:
PubMed [Accessed: 20th October 2011]

H Lee and W J Iglewski., (1984). Cellular ADP-ribosyltransferase with the same
mechanism of action as diphtheria toxin and Pseudomonas toxin A. Journal of
molecular Biology, [e-journal] 81(9), 2703-2707 Available through: PNAS [Accessed:
20th October 2011]