BACTERIAL TOXINS
Bacterial toxins are
exotoxins and endotoxins. Characteristics and
differences of exotoxins and endotoxin are listed in down the page.
EXOTOXINS
Exotoxin producing bacteria
1. Corynebacterium diphtheriae. Strains that carry a temperate bacteriophage are toxigenic causes diphtheria. Exotoxin inhibits protein synthesis and causes cell death. Causes diphtheria.
2. Clostridium tetani. Exotoxin blocks action of inhibitory neurones of spinal cord. Causes tetanus.
3. Clostridium perfringens. (a) Causes gas gangrene. Exotoxin (alpha toxin) has lacithinase activity and thereby causes cell death, (b) Enterotoxin causes hyper secretion of water and electrolytes in diarrhoea.
4. Clostridium botulinum. Exotoxin causes paralysis of deglutination and respiratory muscles. It blocks release of acetylcholine of synapses and neuromuscular junctions. Causes botulism.
5. Vibrio cholerae 01 and 0139. Enterotoxin (Exotoxin) causes hyper secretion of water and electrolytes within gut in diarrhoea.
6. Enterotoxigenic E. coll. Produce enterotoxin (LT- heat labile exotoxin) causes hypersecretion of water and electrolytes within gut.
7. Shigella dysenteriae type 1 (Shiga bacillus). Exotoxin causes acute inflammation.
8. Staphylococcus aureus- some strains : (a) Toxic shock syndrome toxin-1. Causes toxic shock syndrome. (b) Staphylococcal enterotoxin causes toxin type food poisoning and stimulates vomiting centre of brain.
9. Streptococcus pyogenes. Pyrogenic (Erythrogenic) exotoxin causes scarlet fever and toxic shock syndrome.
NOTE : Enterotoxins are exotoxins that are associated with diarrhoea) diseases and food poisoning. Bacteria producing enterotoxins are V. cholerae, enterotoxigenic E. coli (ETEC), some strains of S. aureus, V. parahaemolyticus, Y. enterocolitica, Aeromonas species, and C. perfringens.
Toxoid. Toxoid is modified exotoxin. An exotoxin has two main properties :
(1) toxicity, and
(2) antigenicity. In toxoid, the toxicity of the toxin is destroyed but its antigenicity is preserved. As such toxoids e.g. diphtheria toxoid, tetanus toxoid can be safely used for vaccines. Toxins can be converted to toxoid by different methods e.g. formalin treatment.
EXOTOXINS
Exotoxin producing bacteria
1. Corynebacterium diphtheriae. Strains that carry a temperate bacteriophage are toxigenic causes diphtheria. Exotoxin inhibits protein synthesis and causes cell death. Causes diphtheria.
2. Clostridium tetani. Exotoxin blocks action of inhibitory neurones of spinal cord. Causes tetanus.
3. Clostridium perfringens. (a) Causes gas gangrene. Exotoxin (alpha toxin) has lacithinase activity and thereby causes cell death, (b) Enterotoxin causes hyper secretion of water and electrolytes in diarrhoea.
4. Clostridium botulinum. Exotoxin causes paralysis of deglutination and respiratory muscles. It blocks release of acetylcholine of synapses and neuromuscular junctions. Causes botulism.
5. Vibrio cholerae 01 and 0139. Enterotoxin (Exotoxin) causes hyper secretion of water and electrolytes within gut in diarrhoea.
6. Enterotoxigenic E. coll. Produce enterotoxin (LT- heat labile exotoxin) causes hypersecretion of water and electrolytes within gut.
7. Shigella dysenteriae type 1 (Shiga bacillus). Exotoxin causes acute inflammation.
8. Staphylococcus aureus- some strains : (a) Toxic shock syndrome toxin-1. Causes toxic shock syndrome. (b) Staphylococcal enterotoxin causes toxin type food poisoning and stimulates vomiting centre of brain.
9. Streptococcus pyogenes. Pyrogenic (Erythrogenic) exotoxin causes scarlet fever and toxic shock syndrome.
NOTE : Enterotoxins are exotoxins that are associated with diarrhoea) diseases and food poisoning. Bacteria producing enterotoxins are V. cholerae, enterotoxigenic E. coli (ETEC), some strains of S. aureus, V. parahaemolyticus, Y. enterocolitica, Aeromonas species, and C. perfringens.
Toxoid. Toxoid is modified exotoxin. An exotoxin has two main properties :
(1) toxicity, and
(2) antigenicity. In toxoid, the toxicity of the toxin is destroyed but its antigenicity is preserved. As such toxoids e.g. diphtheria toxoid, tetanus toxoid can be safely used for vaccines. Toxins can be converted to toxoid by different methods e.g. formalin treatment.
ENDOTOXINS
Endotoxins are the integral part of the cell walls
of Gram-negative bacteria, and are liberated when bacteria are disintegrated
(lysed). Cell wall of Gram negative bacteria contain lipopolysaccharides
(LPS,
endotoxin) which consists of
: (1) Lipid A. This is the endotoxin and is the core, and (2) Polysaccharide form coat. This
is the 0 antigen which can induce specific immunity. Physiological,
pathological and clinical effects of endotoxins of different Gram negative
bacteria are similar.
These are :
1. Fever. The endotoxin acts on mononuclear phagocytes (monocytes/macrophages), with liberation of interleukin-1 (endogenous pyrogen). Interleukin-1 acts on thermoregulatory centre. Chill is due to widespread arteriolar and venular constriction.
2. Leucopenia occurs early with onset of fever. It may be followed by leucocytosis.
3. Hypoglycaemia. LPS enhances glycolysis in many cell types and can lead to hypoglycaemia.
4. Hypotension occurs early in Gram-negative bacteraemia.
5. Shock. 'Endotoxic' or 'septic' shock may develop in severe Gram-negative bacteraemia (See chapter 4).
6. Activation of complement. Endotoxin activates complement system by alternative pathway.
7. Disseminated Intravascular Coagulation (DIC). DIC may occur in Gram negative bacteraemia. It is initiated on activation of factor XII (Hageman factor) of coagulation cascade by endotoxin which finally leads to conversion of fibrinogen to fibrin. Endotoxin leads platelets to adhere on vascular endothelium. Endotoxin can activate plasminogen to plasmin which acts on fibrin producing fibrin-split products. Shwartzman phenomenon is taken as a specialized form of DIC.
8. Death may occur due to shock and/or DIC.
NOTE: Peptidoglycan of Gram-positive Bacteria: Peptidoglycan of Gram-positive bacteria released during infection may produce similar activities as LPS of Gram-negative bacteria. However, peptidoglycan is much less potent than LPS.
1. Fever. The endotoxin acts on mononuclear phagocytes (monocytes/macrophages), with liberation of interleukin-1 (endogenous pyrogen). Interleukin-1 acts on thermoregulatory centre. Chill is due to widespread arteriolar and venular constriction.
2. Leucopenia occurs early with onset of fever. It may be followed by leucocytosis.
3. Hypoglycaemia. LPS enhances glycolysis in many cell types and can lead to hypoglycaemia.
4. Hypotension occurs early in Gram-negative bacteraemia.
5. Shock. 'Endotoxic' or 'septic' shock may develop in severe Gram-negative bacteraemia (See chapter 4).
6. Activation of complement. Endotoxin activates complement system by alternative pathway.
7. Disseminated Intravascular Coagulation (DIC). DIC may occur in Gram negative bacteraemia. It is initiated on activation of factor XII (Hageman factor) of coagulation cascade by endotoxin which finally leads to conversion of fibrinogen to fibrin. Endotoxin leads platelets to adhere on vascular endothelium. Endotoxin can activate plasminogen to plasmin which acts on fibrin producing fibrin-split products. Shwartzman phenomenon is taken as a specialized form of DIC.
8. Death may occur due to shock and/or DIC.
NOTE: Peptidoglycan of Gram-positive Bacteria: Peptidoglycan of Gram-positive bacteria released during infection may produce similar activities as LPS of Gram-negative bacteria. However, peptidoglycan is much less potent than LPS.
Characteristics and Differences of Exotoxins and Endotoxins
Endotoxin:
1. Integral part of the cell wall of Gram-negative bacteria. Released on bacterial death and in part during growth. Release is not required for biologic activity.
2. Formed only by Gram-negative bacteria
3. Lipopolysaccharides. Lipid A portion is responsible for toxicity.
4. No specific receptor.
5. Moderately toxic. Fatal to animals in large doses.
6. Relatively heat stable. Toxicity is not destroyed above 60°C for hours.
7. Weakly antigenic. Antibodies are protective.
8. Not converted to toxoid.
9. Synthesis directed by chromosomal genes.
10. Usually produce fever in the host by release of interleukin-1 and other mediators..]
Exotoxins:
1.Excreted by living cells
2. Produced by Gram-positive and Gram-negative bacteria
3. Polypeptides
4. Usually bind to specific receptors on cells
5. Highly toxic. Fatal to animals in very small doses
6. Relatively heat labile. Toxicity destroyed over 60°C
7. Highly antigenic. Stimulate formation of antitoxin. Antitoxin neutralizes the toxin
8. Converted to toxoid by formalin. Toxoid is nontoxic but antigenic. Toxoids are used to immunize, e.g. tetanus toxoid
9. Usually controlled by extra-chromosomal genes, e.g. plasmids, phage gene
10. Usually do not produce fever in the host.
1. Integral part of the cell wall of Gram-negative bacteria. Released on bacterial death and in part during growth. Release is not required for biologic activity.
2. Formed only by Gram-negative bacteria
3. Lipopolysaccharides. Lipid A portion is responsible for toxicity.
4. No specific receptor.
5. Moderately toxic. Fatal to animals in large doses.
6. Relatively heat stable. Toxicity is not destroyed above 60°C for hours.
7. Weakly antigenic. Antibodies are protective.
8. Not converted to toxoid.
9. Synthesis directed by chromosomal genes.
10. Usually produce fever in the host by release of interleukin-1 and other mediators..]
Exotoxins:
1.Excreted by living cells
2. Produced by Gram-positive and Gram-negative bacteria
3. Polypeptides
4. Usually bind to specific receptors on cells
5. Highly toxic. Fatal to animals in very small doses
6. Relatively heat labile. Toxicity destroyed over 60°C
7. Highly antigenic. Stimulate formation of antitoxin. Antitoxin neutralizes the toxin
8. Converted to toxoid by formalin. Toxoid is nontoxic but antigenic. Toxoids are used to immunize, e.g. tetanus toxoid
9. Usually controlled by extra-chromosomal genes, e.g. plasmids, phage gene
10. Usually do not produce fever in the host.
