Pertussis toxin

Pertussis toxin (PT) is a protein-based AB₅-type exotoxin produced by the bacterium "Bordetella pertussis".cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | id = ISBN 0-8385-8529-9 ] PT is involved in the colonization of the respiratory tract and the establishment of infection. Research suggests PT may have a therapeutic role in treating a number of common human ailments including hypertension,cite journal |author=Kost C, Herzer W, Li P, Jackson E |title=Pertussis toxin-sensitive G-proteins and regulation of blood pressure in the spontaneously hypertensive rat |journal=Clin Exp Pharmacol Physiol |volume=26 |issue=5-6 |pages=449–55 |year=1999 |pmid=10386237 |doi=10.1046/j.1440-1681.1999.03058.x] viral inhibition,cite journal |author=Alfano M, Pushkarsky T, Poli G, Bukrinsky M |title=The B-oligomer of pertussis toxin inhibits human immunodeficiency virus type 1 replication at multiple stages |journal=J Virol |volume=74 |issue=18 |pages=8767–70 |year=2000 |pmid=10954581 |doi=10.1128/JVI.74.18.8767-8770.2000] and autoimmune inhibition.cite journal |author=Bagley K, Abdelwahab S, Tuskan R, Fouts T, Lewis G |title=Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway |journal=J Leukoc Biol |volume=72 |issue=5 |pages=962–9 |year=2002 |pmid=12429718]

Mechanism of pathogenesis

PT is an exotoxin with six subunits (named "S1" through "S5"—each complex contains two copies of "S4").cite journal |author=Locht C, Antoine R |title=A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1 subunit |journal=Biochimie |volume=77 |issue=5 |pages=333–40 |year=1995 |pmid=8527486 |doi=10.1016/0300-9084(96)88143-0] 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. 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.cite journal |author=Weiss A, Johnson F, Burns D |title=Molecular characterization of an operon required for pertussis toxin secretion |journal=Proc Natl Acad Sci U S a |volume=90 |issue=7 |pages=2970–4 |year=1993 |pmid=8464913 |doi=10.1073/pnas.90.7.2970]

PT is released from "B. pertussis" in an inactive form. When the B subunit binds to a cell membrane receptor, the A subunit (or "protomer") becomes activated, perhaps through the action of glutathione and ATP.cite book | author = Finger H, von Koenig CHW | title = "Bordetella". "In:" Barron's Medical Microbiology "(Barron S "et al", eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | id = [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1706 (via NCBI Bookshelf)] ISBN 0-9631172-1-1 ] 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.cite journal |author=Burns D |title=Subunit structure and enzymic activity of pertussis toxin |journal=Microbiol Sci |volume=5 |issue=9 |pages=285–7 |year=1988 |pmid=2908558] Since the Gα subunits remain in their GDP-bound, inactive state, they are unable to inhibit adenylyl cyclase, thus keeping levels of adenylyl cyclase and cAMP elevated..

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