Exotoxins

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▶Exotoxins

  • The presence of a large number of microbes do not cause any disease but they maybe block the vessel, heart or passage in lungs etc.
  • But normally pathogen produces a variety of molecule which cause pathogenesis like toxins.
  • Exotoxins are protein released extracellularly as the organisms grow.
  • These toxins move to attach a distance place from the place of infection.
  • Exotoxins are synthesized by specific bacteria contain plasmid or prophages as bearing exotoxins gene.
  • They are heat level proteins and inactivated at 60 degree Celsius to 80 degree Celsius.
  • Exotoxins are easily inactivated by formaldehyde, iodine and other chemicals.
  • Exotoxins are named by the disease.
  • Most exotoxins belong to three categories:-

▶Cytolytic toxins:-

  • Work by enzymatically attack the cell organelles causing lysis.

▶A-B toxins:-

  • Consists of two covalently bonded subunits a and b.
  • The b subunit bind to host cell surface receptor allowing the transfer of a subunit to the host cell and damage the host cell.

▶Superantigen toxin:-

  • This works by simulating a large number of immune response cell resulting massive inflammatory reaction.

▶Cytolytic toxins:-

  • They are also known as membrane disrupting exotoxins.
  • They disrupt the integrity of the plasma membrane.
  • They are of two types:-
  1. the toxin binds to cholesterol:-
  • It is a protein that binds to cholesterol which is a part of the host plasma membrane insert itself into the membrane by forming a channel.
  • This cause the cytoplasmic contents to leak out.
  • Because the concentration of cytoplasm is more than extracellular fluid so water comes into the cell causing swelling and rupture.
  • As an example, some pathogen produces membrane disrupting toxins which kill the phagocytic leukocytes.
  • They are called leukocidin.
  • Mostly produced by pneumococci streptococci and staphylococci.
  • Because the pathogens destroy leukocytes the host resistance decrease.

▶Streptolysin-(SLO)

  • It’s a hemolysin produced by streptococcus.
  • SLO  gets inactivated by O2 so the name was given O(SLO).
  • When they are grown on blood agar and incubated anaerobically a complete clear zone called beta hemolysis.
  • Fan partial clearing of blood is visible it is called Alpha hemolysis.

▶Streptolysin(SLS):-

  • It is a hemolysin produced by streptococcus which is O2 stable so the name is given as SLS.
  • They cause beta hemolysis on an anaerobically grown plate.
  • Hemolysin attack plasma membrane of many cells not only erythrocytes and leukocytes.

▶A-B exotoxins:-

  • They are composed of enzymatic subunits.
  • There are two subunits first one is A which is responsible for the toxic effect when inside the host cell.
  • The second one is B which is known for binding subunit.
  • A is enzymatically active but do not have binding and entry capacity.
  • B can bind to target cell but non-toxic and biologically inactive.
  • B subunit interacts with a specific receptor on the target cell or tissue.

Mechanism:-

  • B subunit inserts into PM and creates a poll for ‘a’ subunit to enter.
  • Another mechanism is receptor-mediated endocytosis.
  • Interceptor mediated endocytosis the B subunit binds to surface receptor P is taken into the cell through clathrin-coated vesicles.
  • The toxin then enters the vesicle membrane and cleaved into two parts.
  • From that, a move to cytosol which is an enzyme catalyzes the addition of an EDP ribose group to elongation factor 2 required in translocation.
  • This modified elongation factor 2 protein can’t participate in the elongation cycle of protein synthesis.•so the cell dies without protein synthesis.

Exotoxins

 

Affect the nervous system and also indirectly cause the enteric symptom. Neurotoxin:-

  • Example staphylococcal enterotoxin B
  • True enterotoxin has defect effect on intestinal mucosa by profuse fluid secretion.
  • B subunit made of five parts arranged in a dough shaped ring.
  • B subunit anchor itself to the p.m. and insert the smaller a subunits into the cell.
  • A subunit activates tissue adenylate cyclase to increase intestinal cycle an AMP concentration.
  • High cyclic amp concentration Max the movement of massive quantities of water and electrolyte from the cell to lumen or gut.
  • Example – vibrio Cholera

▶Exotoxins in disease:-

  • A human exposed to bacteria in three main ways:-
  • Injection of exotoxins -staphylococcus occurs self-limiting
  • Colonization on the mucous membrane and produce exotoxin cause disease at distance place-vibrio Cholera
  • Colonization of a wound then local exotoxins production cause local tissue damage or kill the phagocytic cell which enters the infected area-clostridium perfringens.
Exotoxins
ENTEROTOXIN