Bacterial Toxins

                                        

                                            BACTERIAL TOXINS

Toxin are major determinants of virulence

There are two two type toxin such as

1.    Endotoxins [secreted by Gram negative bacteria (Lipid A)]

2.    Exotoxin

 

Endotoxins: -

This are the cell wall component of Gram-negative bacteria, which generally involved in pyrogen also in inflammation.

 

Exotoxin: -

This are the protein glycoprotein which are secreted by bacteria which are generally enzymes and alter host metabolism

e.g. Diphtheria toxins, cholera toxins, tetanus toxins.

Cholera toxin: -

-        Produce by vibrio cholera a facultative anaerobe which caused disease cholera.

-        Cholera toxin also known as cholerogen

-        The virulence gene are clustered in chromosomal segment called as CTS box.

Gene	Product	Function
Ctx AB	Choler’s toxin	Main toxin in cholera
Zot	Cumulus acuminous	Active Polymerization
Aco	Accessory toxin	Hyper recreation

 

-        Out of these three toxins, the gene product of ctx AB the main cholera toxin and other two toxin preferable accessory toxin

-        The expression of this gene controlled by another gene tax, R.

-        The cholera toxin and type 4 pili are key virulence factor from this bacterium

-        Type 4 pili acts as adhesion molecule which bring the vibrio in close contact of mucous surface

 

Structure of cholera toxin: -

-        Cholera toxin is typical AB type toxin in which there are 1 subunit of A and 5 subunits of AB

-        The molecule weight of A is 23500 and B is 11500

-        The Gm^-1 ganglioside present on crypt cell and villus enter site of intestine serve as receptor for cholera toxin

-        The subunit A is made up of two A₁ and A₂ which are connected each other by disulfide linkage

 

Mechanism of Action: -

-        When cholera toxin is secreated bind to the Gm^-1 ganglioside and A subunit enters into cell.

-        Once enter into the cel the disulphide linkage behaves A_g and A₂ is reduced and two subunit are released from each other

-        The subunit A₁ is active cholera toxin

-        The alter the normal function of G protein

-        The G protein in are involved in signal transduction and ultimetly regulates activation and inactivation at an enzyme which regulates activation and inactivation of an enzyme which regulates the metabolism of cell [Adenylate Cyclase] which regulates the production of cyclic AMP

-        Under normal condition the Amp is produced in this a signal molecule binds to receptor present on cell to release of GDP and binding of GTP

-        The activated G protein (αG protein) then bind to adenylate cyclase and activate it and this activated adenylate cyclase synthesis of CAMP from ATP but when GTP is hydrolyze the αG protein is released form adenylate cyclase and adenylate cyclase is deactivation of this toxin (A₁) permanently activates adenylate cyclase enzyme by altering the activity of G protein

-        Cholera toxin catalyze ADP ribosylation of αG protein (GTP bound form) which is bound to adenylate cyclase permanently.

-        Therefore, concentration of CAMP increases in cell

-        The CAMP regulate the ion traffic and its increased concentration, the cell has 3 effect on ion migration

1] Electrogenic chlorine pump are stimulated causing high amount of cl^- leaving the cell.

2] Na⁺, H⁺ exchange system is blocked.

3] The increased cl^- in lumen intestine increases the HCO₃^-

- The ultimate result of this process is increased concentration of cl^-, HCO₃ and Na⁺ in lumen of intestine [outside cell]

- Therefore, the water present in cell comes out in the lumen

- Therefore, affected patient excrete 1lit of fluid/day

- This result in loss of bodies fluid in feces

- The normal person excrete only 100ml fluid in faces 1 day