Toxins and Toxin Mediated Disease

Endotoxin = Lipopolysaccharide (LPS)

Exotoxins - Classification:

By effects:

• Membrane damaging
• Protein synthesis inhibitors
• Pharmacological

By organ target:

• Neurotoxin.
• Enterotoxin, Cardiac, Hepatic or Renal toxic effects

By mechanism:

• Lipases (a)
• Pore-forming (a)
• ADP-ribosylating
• Cholera, E. coli LT (c, E)
• Diphtheria toxin (b, C,N)
• Psuedomonas Exotoxin A (b)
• Pertussis toxin (c)
• Zinc Proteases
• Tetanus, botulinum
• Glycosyl transferases
• Clostridium difficile
• Others+++ e.g. Adenyl cyclase, superantigenic toxins

Common features of exotoxins:

Active and Binding portions (may be on separate subunits).

Hence same enzyme activity with different Binding specificity produces a different pattern of toxicity.

Similarly, toxins with essentially the same enzyme activity may have active units that have different substrate specificities.

The active subunits often require proteolysis before they are active.

Toxin-mediated disease

• Pathology often distant from site of bacterial growth.
• Protective immunity may be mediated by anti-toxin antibodies alone.
• Disease may be fully reproduced by administering the toxin alone.

Toxin mediated diseases come in 3 forms:

1. Disease due to preformed toxin (toxin formed outside the body)
   e.g. S. aureus food poisoning, botulism (Clostridium botulinum).

2. Disease due (almost) entirely to toxin formation during infection
   e.g. tiphtheria (Corynebacterium diphtheriae), tetanus (Clostridium tetani).

3. Disease to which toxin(s) make a significant contribution but other virulence factors are very important
   e.g. cholera (Vibrio cholerae), whooping cough (Bordetella pertussis).

Examples:

• Gram negative septic (endotoxic) shock, a toxin-cytokine mediated disease caused by any gram negative organism in the bloodstream in high numbers.
• Toxic shock syndrome, a toxin-cytokine mediated disease (Staphylococcus aureus, Streptococcus pyogenes) - only strains producing superantigenic toxins.

Example 7: Diphtheria

• Corynebacterium diphtheriae, Gram positive bacillus causing severe pharyngitis plus heart and nerve pathology.
• Subunit ADP ribosylating toxin which inhibits protein synthesis and damages the respiratory system, heart and nervous system.

Example 9: Cholera

• Vibrio cholerae, Gram negative curved bacillus.
• Subunit ADP-ribosylating toxin leading to massive chloride and water secretion in the small intestine.

© MicrobiologyBytes 2007.