Endotoxin

Toxins

• Endotoxin
  • lipopolysaccharides (LPS) that form part of the bacterial wall
  • cause Gram-negative sepsis
• Exotoxin
  • Exotoxins are peptides that are secreted by bacteria
  • mostly secreted by Gram-positive bacteria
  • Some exotoxins act as superantigens and can trigger dysregulated host immune responses with widespread T-lymphocyte activation
    • Examples
      • Toxic Shock Syndrome (TSS) toxin
        • Released by Staphylococcus aureus causing TSS
        • Pyrogenic exotoxin released by Streptococcus pyogenes, causing streptococcal toxic shock syndrome (STSS)
      • Clostridial myonecrosis (Gas gangrene)
        • Alpha toxin
          • A lecithinase that causes local tissue breakdown, with platelet aggregation, thrombosis and reduced perfusion, extends the area of devitalised tissue
            • Once absorbed systemically, alpha toxin causes haemolysis, cardiac suppression and subsequent toxic shock
        • Multiple other including Theta Toxin
      • Clostridium difficile
        • Exotoxins A and B
          • Both have enterotoxic and cytotoxic activities. Through disruption of the cytoskeleton, hypersecretion of fluid, neutrophil adhesion and local inflammation, they disrupt gut barrier integrity and functionality.
      • Tetanus - Clostridium tetani
        • Tetanus spores enter the body through contaminated trauma.
        • Incubation period of 3–21 days, bacteria divide and release tetanus toxin (tetanospasmin).
        • Tetanospasmin travels via retrograde axonal transport from the peripheries to the spinal cord, where it prevents inhibitory neurotransmitter release.
        • Generalised tetanus may ensue, or it may be localised.
      • Botulism - Clostridium botulinum
        • Botulinum toxin enters presynaptic nerve cells of voluntary muscles and of the autonomic nervous system. In the nerve terminal, they prevent acetylcholine release by inhibiting fusion of its vesicles to the cytosolic membrane.

	Endotoxins	Exotoxins
		Type 1	Type 2	Type 3
Examples of typical diseases	Gram-negative bacteria causing sepsis	Gram-positive cocci causing toxic shock syndromes	Gram-positive anaerobes causing clostridial myonecrosis, Clostridium difficile colitis	Gram-positive anaerobes causing tetanus and botulism
Chemistry	Lipopolysaccharide	Polypeptide	Polypeptide	Polypeptide
Stimulates adaptive immune response	No	Yes	Yes	Yes
Mechanism of action	Interacts with TLR-4 and CD14, activating CD4 cells, causing the release of TNF-α and IL-1	Superantigen activates large numbers of T4-lymphocytes causing exaggerated immune response	Enzymatic or pore-forming activity, affecting cell membranes and cell matrix	A (active) and B (binding) toxins and others that can also affect cell function
Vaccines	No	No	No	Yes; toxoids used as vaccines
Heat stability	Stable at 100°C for >1 h	Destroyed by heat >60°C (except staphylococcal enterotoxin)	Destroyed by heat >60°C	Destroyed by heat >60°C
Typical bacteria	Escherichia coli, Pseudomonas and Klebsiella	Staphylococcus aureus and Streptococcus pyogenes	Clostridium perfringens and Clostridium difficile	Clostridium tetani and Clostridium botulinum