Cholera Toxin, Neurotoxins, and Antitoxins

Cholera Toxin

• An exotoxin produced by Vibrio cholerae.
• Alters regulatory control in gastrointestinal tract cells.
  • The Vibrio bacteria excretes cholera toxin which then binds to a receptor on the outside of the cell and is incorporated into the cell.
  • Changes the way cyclic AMP works, increasing cyclic AMP levels.
    • Cyclic AMP drives electrolytes and water out of the cell.
• Results in significant electrolyte and water loss.
  • Causes up to 10 to 20 liters of diarrhea per day.
  • Can lead to death from diarrhea within a day.

Neurotoxins: Clostridium tetani and Clostridium botulinum

• Exotoxins that affect the nervous system.
• Produced by Clostridium tetani and Clostridium botulinum.
• Among the most potent toxins known.

Clostridium tetani (Tetanus)

• Grows in deep, necrotic puncture wounds where there is dead tissue and no blood flow.
  • Necrotic means that there's no blood flow coming very well to the area. The tissue around where the wound is is dead.
• Anaerobic bacterium.
  • Anaerobic means that they don't like oxygen.
• Exotoxin travels to the nervous system.
  • Bacteria remains localized due to oxygen presence elsewhere.
  • Causes rigid muscle contraction.
• Symptoms:
  • Locked jaw (early symptom).
  • Arching of the back, severe enough to crush spinal bones.
• Mechanism:
  • Normally, neurons release a neurotransmitter to contract muscles, followed by an inhibitory neurotransmitter to stop contraction.
  • Tetanus toxin blocks the inhibitory neurotransmitter, preventing muscle relaxation.
  • Contraction continues and cannot be stopped.
  • Failure of inhibition of motor reflexes.
  • Any sensory stimulation will cause a contraction and you can't stop it and it just keeps on going.
  • Generalized Contractions \rightarrow Death
• Immunizations are available.

Clostridium botulinum (Botulism)

• Has the opposite effect to tetanus.
• Normally, nerves release acetylcholine to cause muscle contraction.
• Botulinum toxin prevents the release of acetylcholine.
• Causes flaccid paralysis (muscles become floppy).
• Applications:
  • Used in cerebral palsy to induce flaccid paralysis in unusually contracted muscles.

Antitoxins

• Neutralize toxins in the body.
• Derived from serum of animals (or humans) exposed to the toxin.
  • The animal's body makes antibodies also known as immunoglobulin; that immunoglobulin will neutralise the toxin before it binds to our cells and causes a problem.
• Administered to provide immediate immunity.
• Essential because the body's natural antibody production takes 7-14 days, while toxins act within a day.