Exotoxin

Source: Wikipedia, the free encyclopedia.
This figure shows that exotoxins are secreted by bacterial cells, Clostridium botulinum for example, and are toxic to somatic cells. Somatic cells have antibodies on the cell wall to target exotoxins and bind to them, preventing the invasion of somatic cells. The binding of the exotoxin and antibody forms an antigen-antibody interaction and the exotoxins are targeted for destruction by the immune system. If this interaction does not happen, the exotoxins bind to the exotoxin receptors that are on the cell surface and causes death of the host cell by inhibiting protein synthesis. This figure also shows that the application of heat or chemicals to exotoxins can result in the deactivation of exotoxins. The deactivated exotoxins are called toxoids and they are not harmful to somatic cells.

An exotoxin is a

endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface
.

They may exert their effect locally or produce systemic effects. Well-known exotoxins include:

tetanospasmin produced by Clostridium tetani. The toxic properties of most exotoxins can be inactivated by heat or chemical treatment to produce a toxoid. These retain their antigenic specificity and can be used to produce antitoxins
and, in the case of diphtheria and tetanus toxoids, are used as vaccines.

Exotoxins are susceptible to

antibodies produced by the immune system, but some exotoxins are so toxic that they may be fatal to the host before the immune system has a chance to mount defenses against them. In such cases, antitoxin, anti-serum containing antibodies, can sometimes be injected to provide passive immunity
.

Types

Many exotoxins have been categorized.[2][3] This classification, while fairly exhaustive, is not the only system used. Other systems for classifying or identifying toxins include:

  • By organism generating the toxin
  • By organism susceptible to the toxin
  • By secretion system used to release the toxin (for example, toxic effectors of type VI secretion system)
  • By tissue target type susceptible to the toxin (
    cardiotoxins
    affect the heart, etc.)
  • By structure (for example, AB5 toxin)
  • By domain architecture of the toxin (for example, polymorphic toxins)
  • By the ability of the toxin to endure in hostile environments, such as heat, dryness, radiation, or salinity. In this context, "labile" implies susceptibility, and "stable" implies a lack of susceptibility.
  • By a letter, such as "A", "B", or "C", to communicate the order in which they were identified.

The same exotoxin may have different names, depending on the field of research.

Type I: cell surface-active

Type I toxins bind to a receptor on the cell surface and stimulate intracellular signaling pathways. Two examples are described below.

Superantigens

cytokines
, which produce the symptoms of toxic shock.

Heat-stable enterotoxins

Some strains of

cyclic GMP
and downstream effects on several signaling pathways. These events lead to the loss of electrolytes and water from intestinal cells.

Type II: membrane damaging

Membrane-damaging toxins exhibit hemolysin or cytolysin activity in vitro. However, induction of cell lysis may not be the primary function of the toxins during infection. At low concentrations of toxin, more subtle effects such as modulation of host cell signal transduction may be observed in the absence of cell lysis. Membrane-damaging toxins can be divided into two categories, the channel-forming toxins and toxins that function as enzymes that act on the membrane.

Channel-forming toxins

Most

channel-forming toxins
, which form pores in the target cell membrane, can be classified into two families: the cholesterol-dependent toxins and the RTX toxins.

  • Cholesterol-dependent cytolysins

Formation of pores by cholesterol-dependent cytolysins (CDC) requires the presence of cholesterol in the target cell. The size of the pores formed by members of this family is extremely large: 25-30 nm in diameter. All CDCs are secreted by the type II secretion system;[4] the exception is pneumolysin, which is released from the cytoplasm of Streptococcus pneumoniae when the bacteria lyse.

The CDCs Streptococcus pneumoniae Pneumolysin,

inflammatory response.[5]
Histone modification does not involve the pore-forming activity of the CDCs.

  • RTX toxins

haemolysin A (HlyA) of E. coli.[citation needed] RTX is also found in Legionella pneumophila.[6]

Enzymatically active toxins

One example is the α toxin of C. perfringens, which causes gas gangrene; α toxin has phospholipase activity.

Type III: intracellular

Type III exotoxins can be classified by their mode of entry into the cell, or by their mechanism once inside.

By mode of entry

Intracellular toxins must be able to gain access to the cytoplasm of the target cell to exert their effects.

  • Some bacteria deliver toxins directly from their cytoplasm to the cytoplasm of the target cell through a needle-like structure. The effector proteins injected by the type III secretion apparatus of Yersinia into target cells are one example.
  • Another group of intracellular toxins is the
    immune response. This allows the body to detect the harmful toxin if it is encountered later, and to eliminate it before it can cause harm to the host. Toxins of this type include cholera toxin, pertussis toxin, Shiga toxin and heat-labile enterotoxin
    from E. coli.

By mechanism

Once in the cell, many of the exotoxins act at the eukaryotic

60S), as protein synthesis inhibitors. (Ribosome structure is one of the most important differences between eukaryotes and prokaryotes, and, in a sense, these exotoxins are the bacterial equivalent of antibiotics such as clindamycin
.)

Other intracellular toxins do not directly inhibit protein synthesis.

  • For example, Cholera toxin ADP-ribosylates, thereby activating tissue adenylate cyclase to increase the concentration of cAMP, which causes the movement of massive amounts of fluid and electrolytes from the lining of the small intestine and results in life-threatening diarrhea.
  • Another example is Pertussis toxin.

Extracellular matrix damage

These "toxins" allow the further spread of bacteria and, as a consequence, deeper tissue infections. Examples are hyaluronidase and collagenase. These molecules, however, are enzymes that are secreted by a variety of organisms and are not usually considered toxins. They are often referred to as virulence factors, since they allow the organisms to move deeper into the hosts tissues.[7]

Medical applications

Vaccinations

Exotoxins have been used to produce vaccines. This process involves inactivating the toxin, creating a

pertussis, tetanus and diphtheria infections, caused by the exotoxin-producing Bordetella pertussis, Clostridium tetani and Corynebacterium diphtheriae respectively.[9] Vaccination with the toxoids generates antibodies against the exotoxins, forming immunological memory as protection against subsequent infections.[8][10] The DPT vaccination may cause adverse side effects, such as swelling, redness and fever, and is contraindicated in some populations.[8] Effective vaccination schedules have reduced rates of mortality linked to pertussis, tetanus and diphtheria but formal controlled trials to test the efficacy of the vaccine have not been conducted.[8] Additionally, pertussis persists endemically[9] and is one of the most common causes of vaccine-preventable deaths.[10]

Cancer treatment

As exotoxins are highly potent, there has been development in their application to cancer treatment. Cancer cells can be eliminated without destroying normal cells like in chemotherapy or radiation by attaching an antibody or receptor ligand to the exotoxin, creating a

cutaneous T-cell lymphoma, an immune system cancer.[12] Further testing to improve clinical efficacy of treatment using recombinant exotoxins continues.[11]

See also

References

  1. ISBN 978-0-07-160402-4
    .
  2. ISBN 978-0-12-621361-4
    .
  3. ^ "Bacterial Pathogenesis: Bacterial Factors that Damage the Host - Producing Exotoxins". Archived from the original on 2010-07-27. Retrieved 2008-12-13.
  4. PMID 16177291
    .
  5. PMID 17675409
    .
  6. PMID 18194518
    .
  7. ISBN 978-0-8053-7590-9
    .
  8. ^
    S2CID 18873223
    .
  9. ^
    PMID 19671937
    .
  10. ^
    PMID 22776216
    .
  11. ^
    PMID 10508704
    .
  12. ^
    PMID 21585657
    .

External links
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