Pertussis toxin (PT) is a protein-based AB₅-type exotoxin produced by the bacterium Bordetella pertussis,^[1] which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection.^[2] Research suggests PT may have a therapeutic role in treating a number of common human ailments including hypertension,^[3] viral inhibition,^[4] and autoimmune inhibition.^[5]

[edit] Structure

PT is an exotoxin with six subunits (named S1 through S5—each complex contains two copies of S4).^[6][7] The subunits are arranged in a A-B structure: the A component is enzymatically active and is formed from the S1 subunit, while the B component is the receptor-binding portion and is made up of subunits S2–S5.^[7] The subunits are encoded by ptx genes encoded on a large PT operon that also includes additional genes which encode Ptl proteins: Together these proteins form the PT secretion complex.^[8]

[edit] Mechanism of pathogenesis

PT is released from B. pertussis in an inactive form. Following PT binding to a cell membrane receptor, it is taken up in an endosome, after which it undergoes retrograde transport to the trans-Golgi network and endoplasmic reticulum^[9]. At some point during this transport, the A subunit (or protomer) becomes activated, perhaps through the action of glutathione and ATP.^[10] PT catalyzes the ADP-ribosylation of the α subunits of the heterotrimeric G proteins G_i, G_o, and G_t. This prevents the G proteins from interacting with G protein-coupled receptors on the cell membrane, thus interfering with intracellular communication.^[11] The Gi subunits remain locked in their GDP-bound, inactive state, thus unable to repress acadenyl cyclase activity, leading to increased cellular concentrations of cAMP.

Increased intracellular cAMP affects normal biological signalling and is responsible for the neurogenic disorder that culminates in the paroxysmal, characteristic whooping cough.

The toxin causes several systemic effects, among which is an increased release of insulin, causing hypoglycemia.

[edit] References