570 Chapter 23 Respiratory System Infections absorbed by the bloodstream. The gray-white membrane that forms in the throat of people with diphtheria is made up of clotted blood along with epithelial cells of the host mucous membrane and the leukocytes that congregate during inflammation, killed by exotoxin released from C. diphtheriae. This membrane may come loose and obstruct the airways, causing the patient to suffocate. Entry of the toxin into the blood-stream results in damage to the heart, nerves, and kidneys.
The diphtheria toxin is a large protein released from the bacterium in an inactive form. It is cleaved extracellularly into two chains, A and B, which remain joined by a disulfide bond. The B chain attaches to specific receptors on a host cell membrane, and the entire molecule is taken into the cell by endocytosis (figure 23.6). Cells that lack the appropriate receptors do not take up the toxin and are unaffected by it. This receptor specificity explains why some tissues of the body are not affected in diphtheria, while others such as the heart, kidneys, and nerves are severely damaged.
Once the toxin molecule is inside the cell, the A chain separates from the B chain and becomes an active enzyme. This enzyme catalyses a chemical reaction that inactivates elongation factor 2 (EF-2), a substance required for movement of the ribosome on mRNA (see figure 23.6). This halts protein synthesis, and the cell dies. Since the toxin A chain is an enzyme, it is not consumed in the process, so one or two molecules of toxin can inactivate essentially all the cell's elongation factor 2. This explains the extreme potency of diphtheria toxin. ■ A-B toxins, p. 472 ■ elongation factor, p. 178
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