Bordetella Pertussis
BACTERIOLOGY
B. pertussis is a tiny (0.5 to 1.0 μm), Gram-negative coccobacillus morphologically much like Haemophilus. Growth requires a special medium supplemented withnicotinamide and other additives such as charcoal, which is thought to neutralize the effect of inhibitory compounds present in standard bacteriologic media. Under the best conditions, growth is still slow, requiring 3 to 7 days for isolation. The organism is also very susceptible to envi-ronmental changes and survives only briefly outside the human respiratory tract.
The cell wall has the structure typical of Gram-negative bacteria, although the outer membrane lipopolysaccharide differs significantly in structure and biologic activity from that of the Enterobacteriaceae. The surface exhibits a rod-like protein called the filamen-tous hemagglutinin (Fha) becauseofits abilitytobindto andagglutinate erythrocytes.Fha has strong adherence qualities, based on domains in its structure that interact with an amino acid sequence (arginine, glycine, aspartic acid) present in host integrins, epithelial cells, and macrophages. The organism surface also contains surface pili and the outer membrane includes a protein called pertactin.
Pertussis toxin (PT) is themajorvirulencefactor ofB. pertussis.Itis anA-B toxin pro-duced from a single operon as an enzymatic subunit and five distinct binding subunits that are assembled into the complete toxin on the bacterial surface. The binding subunits me-diate attachment of the toxin to carbohydrate moieties on the host cell surface. The enzy-matic subunit is then internalized and ADP-ribosylates a G-protein that affects adenylate cyclase activity. Unlike cholera toxin, which in essence keeps cyclase activity “turned on,” pertussis toxin freezes the opposite side of the regulatory circuit and cripples the ca-pacity of the host cell to inactivate cyclase activity. Other intracellular effector pathways are also disrupted by the G-protein modification. The binding subunits have a biologic ef-fect on lymphocytes and other cells independent of the enzymatic function of the toxin.
Another potent toxin, an invasive adenylatecyclase, enters host cells and catalyzes the conversion of host cell ATP to cyclic AMP at levels far above what can be achieved by normal mechanisms. This enzyme is hemolytic and interferes with cellular signaling, chemotaxis, superoxide generation, and microbicidal function of immune effector cells, including polymorphonuclear leukocytes and monocytes. It can also induce programmed cell death (apoptosis). Remarkably, after the adenylate cyclase enters the cell, it requires activation by calmodulin, a eukaryotic Ca2+-binding protein. Such activation of a bacte-rial enzyme by an intracellular mammalian protein is unusual, but is also seen with an-other bacterial adenylate cyclase, anthrax toxin . Tracheal cytotoxin is essentially fragments of cell-wall peptidoglycan (1,6-anhydromuramic acid-N-acetyl-glucosamine-tetrapeptide). The fragments are released by multiplying bacterial cells and cause the death of ciliated tracheal cells. This cytotoxin is similar, if not identical to, one produced by Neisseriagonorrhoeae .
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