Exotoxins - Biology Ease

▶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:-

▶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:-

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.

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.