Pathogenesis

Bordetella pertussis enters the respiratory tract with inspired air and attaches specifically to ciliated cells of the respiratory epithelium. Among the proteins present on the bacterial surface, pertussis toxin (Ptx) and filamentous hemagglutinin (Fha) are probably the main ones involved in attachment.

The areas colonized by B. pertussis include the nasopharynx, trachea, bronchi, and bronchioles. The violent symptoms arise because of involvement of the passageways of the lower respiratory tract. The organisms grow in dense masses on the epithelial surface, but they do not invade. Mucus secretion increases markedly, while ciliary action declines precipitously, and patches of ciliated cells slough off. Only the cough reflex remains for clearing the secretions. Some of the bronchioles become completely obstructed, resulting in small areas of collapsed lung. Others, because of spasm or mucus plugging, let air enter but not escape, causing hyperinflation. Paroxysmal coughing causes hemorrhages in the brain, and seizures can occur. Pneumonia due to B. pertussis or, more commonly, secondary bacterial infection is the chief cause of death.

A number of toxic products of B. pertussis probably play a role in its pathogenesis. Pertussis toxin (Ptx), mentioned earlier for its role in colonization, is an A-B toxin. Figure 23.14 shows the steps involved in the toxin's action. First, the B portion attaches specifically to receptors on the host cell surface. Second, the A portion is transferred through the cytoplasmic membrane of the host cell, becoming an active ribosylating enzyme in the process. The activated A portion of the Ptx toxin inactivates the G protein normally responsible for initiating a decrease in cyclic adenosine monophosphate (cAMP) synthesis, thereby allowing maximum production of cAMP. Unregulated cAMP production causes marked increase in mucus output, decreased killing ability of phagocytes, massive release of lymphocytes into the bloodstream, ineffectiveness of natural killer cells, and low blood sugar. Invasive adenylate cyclase, another B. pertussis toxin, also causes an increase in cAMP production. ■ A-B toxins, p. 472 ■ cAMP, p. 185

Tracheal cytotoxin produced by B. pertussis acts with endotoxin to cause release ofnitric oxide (NO) from goblet cells. The NO causes ciliated epithelial cells to die and slough off. Tracheal cytotoxin also causes the release of interleukin-1 (IL-1), a fever-causing cytokine. ■ interleukin-1, p. 380

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