Exotoxins and endotoxins
Exotoxins are secreted by bacteria where as endotoxins are only released following lysis of the cell. Exotoxins are generally released by Gram positive bacteria with the notable exceptions of Vibrio cholerae and some strains of E. coli
It is possible to classify exotoxins by their primary effects:
Pyrogenic toxins
Pyrogenic toxins stimulate the release of endogenous cytokines resulting in fever, rash etc. They are superantigens which bridge the MHC class II protein on antigen-presenting cells with the T cell receptor on the surface of T cells resulting in massive cytokine release.
Enterotoxins
Enterotoxins act on the gastrointestinal tract causing one of two patterns of illness:
Neurotoxins
Neurotoxins act on the nerves (tetanus) or the neuromuscular junction (botulism) causing paralysis.
Tissue invasive toxins
Miscellaneous toxins
Endotoxins
Endotoxins are lipopolysaccharides that are released from Gram-negative bacteria such as Neisseria meningitidis.
It is possible to classify exotoxins by their primary effects:
- pyrogenic toxins
- enterotoxins
- neurotoxins
- tissue invasive toxins
- miscellaneous toxins
Pyrogenic toxins
Pyrogenic toxins stimulate the release of endogenous cytokines resulting in fever, rash etc. They are superantigens which bridge the MHC class II protein on antigen-presenting cells with the T cell receptor on the surface of T cells resulting in massive cytokine release.
| Organism | Toxin | Notes |
|---|---|---|
| Staphylococcus aureus | Toxic shock syndrome (TSST-1 superantigen) toxin | Results in high fever, hypotension, exfoliative rash |
| Streptococcus pyogenes | Streptococcal pyrogenic exotoxin A & C | Results in scarlet fever |
Enterotoxins
Enterotoxins act on the gastrointestinal tract causing one of two patterns of illness:
- diarrhoeal illness
- vomiting illness ('food poisoning')
| Organism | Toxin | Notes |
|---|---|---|
| Vibrio cholerae | Cholera toxin | Causes activation of adenylate cyclase (via Gs) leading to increases in cAMP levels, which in turn leads to increased chloride secretion and reduced sodium absorption |
| Shigella dysenteriae | Shiga toxin | Inactivates 60S ribosome → epithelial cell death |
| Escherichia coli | 1. Heat labile toxin 2. Heat stabile toxin | 1. Activates adenylate cyclase (via Gs), increasing cAMP → watery diarrhoea 2. Activates guanylate cyclase, increasing cGMP → watery diarrhoea |
| Staphylococcus aureus | Staphylococcus aureus enterotoxin | Vomiting and diarrhoeal illness lasting < 24 hours |
| Bacillus cereus | Cereulide | Potent cytotoxin that destroys mitochondria. Causes a vomiting illness which may present within 4 hours of ingestion |
Neurotoxins
Neurotoxins act on the nerves (tetanus) or the neuromuscular junction (botulism) causing paralysis.
| Organism | Toxin | Notes |
|---|---|---|
| Clostridium tetani | Tetanospasmin | Blocks the release of the inhibitory neurotransmitters GABA and glycine resulting in continuous motor neuron activity → continuous muscle contraction → lockjaw and respiratory paralysis |
| Clostridium botulinum | Botulinum toxin | Blocks acetylcholine (ACh) release leading to flaccid paralysis |
Tissue invasive toxins
| Organism | Toxin | Notes |
|---|---|---|
| Clostridium perfringens | α-toxin, a lecithinase | Causes gas gangrene (myonecrosis) and haemolysis |
| Staphylococcus aureus | Exfoliatin | Staphylococcal scalded skin syndrome |
Miscellaneous toxins
| Organism | Toxin | Notes |
|---|---|---|
| Corynebacterium diphtheriae | Diphtheria toxin | ADP ribosylates elogation factor (EF-2), resulting in inhibition, causing a 'diphtheric membrane' on tonsils caused by necrotic mucosal cells. Systemic distribution may produce necrosis of myocardial, neural and renal tissue |
| Pseudomonas aeruginosa | Exotoxin A | Also inhibits EF-2 by the same mechanism as above |
| Bacillus anthracis | Oedema factor (EF) | Forms a calmodulin-dependent adenylate cyclase which increases cAMP, impairing the function of neutrophils/macrophages → reduced phagocytosis |
| Bordetella pertussis | Pertussis exotoxin | Inhibits Gi leading to increases in cAMP levels, impairing the function of neutrophils/macrophages → reduced phagocytosis |
Endotoxins
Endotoxins are lipopolysaccharides that are released from Gram-negative bacteria such as Neisseria meningitidis.