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A classic method of detecting endotoxin is by using the Limulus amebocyte lysate (LAL) test . In this procedure, the blood cells (amebocytes) of the horseshoe crab ( Limulus polyphemus ) is mixed with a patient’s serum. The amebocytes will react to the presence of any endotoxin. This reaction can be observed either chromogenically (color) or by looking for coagulation (clotting reaction) to occur within the serum. An alternative method that has been used is an enzyme-linked immunosorbent assay ( ELISA ) that uses antibodies to detect the presence of endotoxin.
Unlike the toxic lipid A of endotoxin, exotoxin s are protein molecules that are produced by a wide variety of living pathogenic bacteria. Although some gram-negative pathogens produce exotoxins, the majority are produced by gram-positive pathogens. Exotoxins differ from endotoxin in several other key characteristics, summarized in [link] . In contrast to endotoxin, which stimulates a general systemic inflammatory response when released, exotoxins are much more specific in their action and the cells they interact with. Each exotoxin targets specific receptors on specific cells and damages those cells through unique molecular mechanisms. Endotoxin remains stable at high temperatures, and requires heating at 121 °C (250 °F) for 45 minutes to inactivate. By contrast, most exotoxins are heat labile because of their protein structure, and many are denatured (inactivated) at temperatures above 41 °C (106 °F). As discussed earlier, endotoxin can stimulate a lethal inflammatory response at very high concentrations and has a measured LD 50 of 0.24 mg/kg. By contrast, very small concentrations of exotoxins can be lethal. For example, botulinum toxin , which causes botulism , has an LD 50 of 0.000001 mg/kg (240,000 times more lethal than endotoxin).
| Comparison of Endotoxin and Exotoxins Produced by Bacteria | ||
|---|---|---|
| Characteristic | Endotoxin | Exotoxin |
| Source | Gram-negative bacteria | Gram-positive (primarily) and gram-negative bacteria |
| Composition | Lipid A component of lipopolysaccharide | Protein |
| Effect on host | General systemic symptoms of inflammation and fever | Specific damage to cells dependent upon receptor-mediated targeting of cells and specific mechanisms of action |
| Heat stability | Heat stable | Most are heat labile, but some are heat stable |
| LD 50 | High | Low |
The exotoxins can be grouped into three categories based on their target: intracellular targeting, membrane disrupting, and superantigens. [link] provides examples of well-characterized toxins within each of these three categories.
| Some Common Exotoxins and Associated Bacterial Pathogens | |||
|---|---|---|---|
| Category | Example | Pathogen | Mechanism and Disease |
| Intracellular-targeting toxins | Cholera toxin | Vibrio cholerae | Activation of adenylate cyclase in intestinal cells, causing increased levels of cyclic adenosine monophosphate (cAMP) and secretion of fluids and electrolytes out of cell, causing diarrhea |
| Tetanus toxin | Clostridium tetani | Inhibits the release of inhibitory neurotransmitters in the central nervous system, causing spastic paralysis | |
| Botulinum toxin | Clostridium botulinum | Inhibits release of the neurotransmitter acetylcholine from neurons, resulting in flaccid paralysis | |
| Diphtheria toxin | Corynebacterium diphtheriae | Inhibition of protein synthesis, causing cellular death | |
| Membrane-disrupting toxins | Streptolysin | Streptococcus pyogenes | Proteins that assemble into pores in cell membranes, disrupting their function and killing the cell |
| Pneumolysin | Streptococcus pneumoniae | ||
| Alpha-toxin | Staphylococcus aureus | ||
| Alpha-toxin | Clostridium perfringens | Phospholipases that degrade cell membrane phospholipids, disrupting membrane function and killing the cell | |
| Phospholipase C | Pseudomonas aeruginosa | ||
| Beta-toxin | Staphylococcus aureus | ||
| Superantigens | Toxic shock syndrome toxin | Staphylococcus aureus | Stimulates excessive activation of immune system cells and release of cytokines (chemical mediators) from immune system cells. Life-threatening fever, inflammation, and shock are the result. |
| Streptococcal mitogenic exotoxin | Streptococcus pyogenes | ||
| Streptococcal pyrogenic toxins | Streptococcus pyogenes |
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