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Pertussis toxin

Micro > Bacteriology > Pathogenic mechanisms > Toxins
Pertussis toxin (Ptx)

a. Source organism
i. Bordetella Pertussis, a gram-negative bacterium, aerobic, pathogenic, encapsulated coccobacillus that lies in lung and trachea epithelial cells. The organism is oxidase positive and non-motile.

b. Structure
i. AB5 exotoxin
ii. A subunit is called a ADP ribosyl transferase
iii. B (S2-S5) subunits bind to the carbohydrates on the surface of the host cell

c. Mechanism: inhibition of G protiens, leading to increased cAMP production
i. The protein PTx, is released from Bordetella Pertussis and binds to the sulfatides molecules on cilia of epithelial cells. The binding causes the cilia to stop beating. Because the cilia becomes non-functional, it is not clear debris from lungs, which causes the coughing associated with Whopping cough.  
ii. This occurs through binding of the PTx complex to the cell. The B subunits binds to the surface carbohydrates and the A subunits enters into the cell’s cytoplasm through direct entry.  The A subunit then Inhibits the G-protein’s ability to regulate the conversion of ATP to cAMP as it transfers ADP ribosyl portion of NAD  to the Gi . This allows for Adenylate cyclase to run without interruption of Gi .  Without the regulation, there is an overload in conversion. This leads to disturbance in cell signaling and inability to prevent infection.  
iii.  Toxin will cause problems with cellular function such as phagocytic activities ( chemotaxis, engulfment, oxidative burst, and bacterial killing)
iv. Systemically it will cause increased insulin production and sensitivity to histamine. ( increased cAMP production)


d. Prevention (behaviors, vaccination, etc.)
i. The bacteria is treated with macrolide antibiotic.
To avoid getting exposed to the toxin there is a vaccine known as Acceular Pertussis Vaccine. This is a part of a series of vaccines know as the TdAP given in adults and the DPT given to children.  

e. Disease produced
i. Major disease : Pertussis also known as Whooping cough or 100 days’ cough
ii. Other effects: Hypoglycemia, Hypotension, Shock


Related concepts
  1. Pertussis
  2. gram-negative
  3. Whooping cough
  4. DPT
  5. Pertussis toxin
  6. Bordetella Pertussis

Additional Web links:
1.       http://www.nfid.org/idinfo/pertussis/6-pertussis-pathogenesis.pdf
a.       Short article on pertussis as a whole and how short summaries on the other toxins that are present and associated with the disease.
2.       http://textbookofbacteriology.net/pertussis_2.html
a.       More detailed description of how the toxin works and what is effects
3.       http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/pert.pdf
a.           Discusses the vaccine that is used for pertussis as well as how it is treated in the U.S.
 
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