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Pertussis toxin (PTx) is a major virulence factor and protein exotoxin produced by the bacterium Bordetella pertussis, which causes the respiratory disease known as pertussis or whooping cough [StatPearls, 2023]. It is an AB5-type toxin consisting of an enzymatically active A-subunit (S1) and a pentameric B-subunit (S2-S5) that facilitates binding to host cell receptors [UniProt, 2024]. The toxin's primary biological function is the ADP-ribosylation of the alpha subunits of inhibitory G-proteins (Gi/o), which prevents them from inhibiting adenylate cyclase, leading to increased intracellular cyclic AMP levels and disrupted cellular signaling [PubChem, 2024]. This biochemical activity results in systemic effects such as lymphocytosis and the suppression of the host's innate immune response, facilitating bacterial colonization [PubMed, 2021]. In the context of immunization, the toxin is chemically or genetically detoxified to produce pertussis toxoid, a key component of acellular pertussis vaccines like DTaP and Tdap [CDC, 2023]. These vaccines work by stimulating the production of neutralizing antibodies that bind to the toxin, preventing its entry into host cells and neutralizing its enzymatic activity, thereby providing protection against the severe manifestations of the disease [WHO, 2022].
The toxoid acts as an immunogen to stimulate the production of neutralizing antibodies (IgG) that bind to the native Pertussis toxin, thereby blocking its ability to bind to host cell receptors and preventing the ADP-ribosylation of inhibitory G-proteins.
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