Toxins

toxins detail in brief..

1. TOXINS Submitted to: Submitted by: Dr Monika Asthana Garima jain Prashant sharma M.Sc Biotchnology First sem

2. Overview What are toxins? Types Of Toxins Exotoxin Type of Exotoxin Medical application Endotoxin Effects of endotoxin

3. WHAT ARE TOXINS? A toxin [Latin toxicum , poison] is a substance, such as a metabolic product of the organism, that alters the normal metabolism of host cells with deleterious effects on the host. Toxins can be small molecules, peptides or proteins that are capable of causing disease on contact with or absorption by  body tissues  interacting with biological  macromolecules such as  enzymes  or  cellular receptors . Toxins vary greatly in their  toxicity , ranging from usually minor (such as a  bee   sting ) to almost immediately deadly (such as  botulinum toxin ).

4. Types of toxins Toxins produced by bacteria can be divided into two main categories: Exotoxins Endotoxins

5. Exotoxins versus Endotoxins

6. exotoxins Exotoxins are soluble, heat-labile, proteins (a few are enzymes) that usually are released into the surroundings as the bacterial pathogen grows. Generally, exotoxins are produced by gram-positive bacteria, although some gram-negative bacteria also make exotoxins. Often exotoxins may travel from the site of infection to other body tissues or target cells in which they exert their effects.

7. Type of exotoxin Exotoxins can be grouped into four types based on their structure and physiological activities: AB Toxins Specific Host Site Exotoxins Membrane Disrupting Super Antigens

8. Ab toxins It is composed of two parts, where A is the enzymes that disrupts some cell activity, while B-binds surface receptors to bring A into the host cell, e.g., botolinum and tetanus toxin.

9. Ab exotoxin transport mechanism

10. Specific host site exotoxin It is categorized on the basis of affected site neurotoxins (nerve tissue) enterotoxins (intestinal mucosa) cytotoxins (general tissues)

11. neurotoxin Neurotoxins usually are ingested as preformed toxins that affect the nervous system and indirectly cause enteric (pertaining to the small intestine) symptoms. Examples include staphylococcal enterotoxin B, Bacillus cereus emetic toxin [Greek emetos , vomiting], and botulinum toxin.

12. enterotoxin The classic enterotoxin, cholera toxin ( choleragen ), has been studied extensively. It is anAB toxin. The B subunit is made of five parts arranged as a donut-shaped ring. The genes for this enterotoxigenicity are encoded on a filamentous phage within Vibrio cholera.

13. cytotoxin Cytotoxins have a specific toxic action upon cells/tissues of special organs and are named according to the type of cell/tissue or organ for which they are specific. Examples include nephrotoxin (kidney), hepatotoxin (liver), and cardiotoxin (heart).

14. Membrane disrupting exotoxin It lyses host cells by disrupting the integrity of the plasma membrane. There are two subtypes of membrane disrupting exotoxins. 1.A channel-forming (pore-forming) type of exotoxin   The first, is a protein that binds to the cholesterol portion of the host cell plasma membrane inserts itself into the membrane, and forms a channel (pore). This causes the cytoplasmic contents to leak out. Also, because the osmolality of the cytoplasm is higher than the extracellular fluid, this causes a sudden influx of water into the cell, causing it to swell and rupture.

15. 2. A phospholipid-hydrolyzing phospholipase exotoxin   Phospholipases remove the charged head group from the lipid portion of the phospholipids in the host-cell plasma membrane. This destabilizes the membrane so that the cell lyses and dies. One example of the pathogenesis caused by phospholipases is observed in the disease gas gangrene. In this disease, the Clostridium perfringens _-toxin almost completely destroys the local population of white blood cells (that are drawn in by inflammation to fight the infection) through phospholipase activity.

16. Super antigens They are the bacterial proteins that cause proliferation of T-cells and release of cytokines excessive cytokines can cause fever, nausea, vomiting, diarrhoea, shock and death (septic shock), e.g., toxic shock syndrome (staphylococcus), e.g., enterotoxins: staphylococcal food poisoning.

17. MEDICAL APPLICATION OF EXOTOXIN Vaccinations Exotoxins have been used to produce vaccines. This process involves inactivating the toxin, creating a  toxoid  that does not induce toxin-related illness and is well-tolerated. A widely used toxoid vaccine is the  DPT vaccine , which is usually administered in multiple doses throughout childhood with  adjuvants  and  boosters  for long-term immunity. DPT vaccine protects against  pertussis ,  tetanus  and  diphtheria  infections, caused by the exotoxin-producing  Bordetella pertussis ,  Clostridium tetani  and  Corynebacterium diphtheriae respectively . 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  recombinant toxin  that is targeted to certain cells. The cancer cell is killed once the toxin is internalized; for example,  Pseudomonas exotoxin  disrupts protein synthesis after cellular uptake. Multiple versions of recombinant exotoxin A, secreted by  Pseudomonas aeruginosa , have entered clinical trials against tumor growth but have yet to be approved by  Food and Drug Administration . A recombinant diphtheria exotoxin has been approved by the  FDA  for treatment of  cutaneous T-cell lymphoma , an immune system cancer. Further testing to improve clinical efficacy of treatment using recombinant exotoxins continues.

18. endotoxin They are the part of the outer membrane portion of the cell wall of gram negative bacteria, e.g., Lipopolysaccharide (LPS) which is released when dead cells lyse in blood, causes macrophages to release high levels of cytokines resulting is chills, fever, weakness, aches, small blood clots, tissue necrosis, shock and death. The toxic component of the LPS is the lipid portion, called lipid A. Lipid A is not a single macromolecular structure but appears to be a complex array of lipid residues. The lipid A component exhibits all the properties associated with endotoxicity and gram-negative bacteremia.

19. Effects of endotoxin Fever is induced by interleukin-1, produced by the liver in response to endotoxin, acting on the temperature-regulating hypothalamus. The action of lipopolysaccharide on platelets and activation of Hageman's factor causes disseminated intravascular coagulation with ensuing ischaemic tissue damage to various organs. Septic shock occurs during severe infections with Gram-negative organisms when bacteria or lipopolysaccharide enter the bloodstream.

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