Types of exotoxin and list of exotoxins

Exotoxins are proteins produced by both gram-positive bacteria and gram-negative bacteria. There are different types of exotoxin. They are considered to be among most lethal substances as they can easily disseminate in blood for their high solubility. A little amount of exotoxins is sufficient to be a lethal dose. For example, 1mg of botulinum toxins is enough to kill 1 million guinea pigs. Exotoxins stimulate the production of antitoxins as well as potential immune response. Treatment of exotoxins with heat or formaldehyde or Iodine or other chemicals makes it loose of pathogenicity but retain its antigenicity. So it can be used as toxoid or vaccines. In this context three types of exotoxins are discussed with their target cells, mechanism of actions and diseases caused by them.

1. A-B toxin:

A-B toxins are the polypeptides composed of part A and part B. Part A is an active enzymatic component taking part in altering the functions of host cells through inhibition of protein synthesis. Part B is a binding component which mediates the attachment of the toxin to the receptors of host cells.

Bacteria that produce exotoxins: Clostridium tetani, Clostridium diphtheria, Vibrio cholerae, S. aureus.

Toxins: Tetanospasmin, Diphtheria toxin, Cholera toxin, Exfoliatin.

Target cells: Different types of cells throughout the body.

Mechanisms: Different toxins show different mechanisms of actions. Few of them are as below:

  • Tetanospasmin inhibits release of inhibitory neurotransmitters.
  • Diphtheria toxins cause ADP ribosylation of EF-2 resulting in inhibition of protein synthesis.
  • Cholera toxins cause ADP ribosylation of adenylate cyclase, leading to rising in cyclic AMP.
  • Neurotoxin prevents the transmission of nerve impulses: flaccid paralysis results.
  • Neurotoxin blocks nerve impulses to muscle relaxation pathway: results in uncontrollable muscle contractions.
  • Cytotoxin inhibits protein synthesis, especially in nerve, heart, and kidney cells.
  • Enterotoxin causes secretion of large amounts of fluids and electrolytes that result in diarrhea.
  • Exfoliatin is a protease that break down desmoglein protein in desmosomes of skins causing scalded skin syndromes.

Diseases: Spastic paralysis Myopathy, Polyneuropathy, Profuse watery diarrhea
Botulism, Tetanus, Diphtheria, Scalded skin syndrome, Cholera, Traveler’s diarrhea, Anthrax.

2. Membrane-disrupting Toxins:

Membrane-disrupting toxins are the toxins that cause damage to host cells by breaking down the structure of their plasma membranes or by forming protein channels or by disrupting the phospholipids.

Bacteria that produce exotoxins: Staphylococcus aureus, Listeria monocytogenes, Clostridium perfringens, Clostridium difficile.

Toxins: Leukocidin, α-Toxin (lecithinase),  Hemolysin, Listeriolysin, Perfringolysin-O, Streptolysins. Streptolysin O and Streptolysin L.

Target cells: Many cell types including erythrocytes, phagocytic leukocytes and macrophages.

Mechanisms: Different toxins show different mechanisms of actions. Few of them are as below:

  • Leukocidins and Hemolysins destroy their target cells (leukocytes and erythrocytes respectively) by forming protein channels in the plasma membrane of their target cells.
  • The alpha toxin such as lecithinase causes lysis of cell membranes by breaking down lecithin into phosphorylcholine and diglyceride.
  • Phospholipase removes polar head groups from phospholipids.
  • Cytotoxin causes the destruction of massive red blood cell (hemolysis) and destroys host cell cytoskeleton.
  • Enterotoxin causes the release of fluids and electrolytes resulting in diarrhea.

Diseases: Tissue necrosis, Gas gangrene, Food poisoning, Antibiotic-associated diarrhea.

 

3. Superantigens:

Superantigens are the antigens that stimulate the production of a large amount of T cell and also stimulate these T cells to produce a large amount of cytokine.

Bacteria that produce exotoxins (superantigens):  Streptococcus pyogenes, Staphylococcus aureus.

Superantigens/toxins:  Streptococcal pyogenic exotoxin, Toxic shock syndrome toxin, Staphylococcal enterotoxin A (SEA).

Target cells:  T cells, macrophages.

Mechanisms: Different toxins/superantigens show different mechanisms of actions. Few of them are as below:

  • Both streptococcal pyogenic exotoxin and toxic shock syndrome toxin cause T cell stimulation, the ­release of cytokines (IL-1, IL-2, TNF), possible enhancement of LPS activities.
  • Released cytokines stimulate enteric nervous systems to activate vomiting center in the brain.
  • Enterotoxin causes secretion of fluids and electrolytes that results in diarrhea.
  • The toxin causes secretion of fluids and electrolytes from capillaries that decreases blood volume and lowers blood pressure.

Diseases: Fever, rash, nausea, vomiting, diarrhea toxic shock-like syndrome, Toxic shock syndrome, food poisoning.

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