Pathogenesis of Vibrio cholera

August 17, 2018

The sequence of events leading to cholera is basically simple and confined to the gut.
The food and drink contaminated by cholera vibrios if ingested results to disease though small dosage is present.
The organisms begin to multiply in the alkaline medium of the small intestine after passing the acid barrier of the stomach juices.
The incubation period varies from 6 hours to 3 days.
The human vomitus and faeces or carriers are the main sources of infection.
A well-defined sequence of events occurs following the ingestion of V. cholera. They are as follows:

a) Adherence and colonization

Virulent forms of V. cholera attach to the epithelium of microvilli at the brush border no sooner it crosses the acid barrier.
After that, they multiply increasing their number.

b) Secretion of cholera toxin

As they multiply, they produce a potent exotoxin called enterotoxin.
Toxin is produced in close proximity to its specific receptors (GM1 ganglioside) on cell membrane lining the villi and crypts of the small intestines.

Image source: slideshare

c) Activation of the A1 subunit

After there is binding of the B unit to the receptor of the cell membrane, the A subunit dissociates from the B subunit.
The cell membrane gets penetrated during this dissociation.
There are two subunits of A-unit: A1 and A2 which are joined by disulphide bond.
The bond between A1 and A2 subunits is broken down and subunit A1 gets activated.
The ADP ribose is transferred from a nicotinamide adenine dinucleotide (NAD) to a guanosine triphosphate (GTP)-bindind protein by enzymatic action of activated A1 subunit.
The adenyl cyclase activity gets regulated by the above event.
Adenyl cyclase activity of the cell increases because of the normal GTP “turn off” mechanism is inhibited.
This results in an increase and accumulation of intracellular cyclic 3’, 5’-adenosine monophosphate (cAMP).

Inhibition of reabsorption of Na⁺, K⁺and Cl^– ions by cells lining the villi, together with
Hyper-secretion of Cl^–and HCO₃^–

The above activities cause a net loss of sodium, potassium and sodium bicarbonate into the intestine, with a corresponding fluid loss to maintain the isotonicity of the intestinal fluid.
There is purging diarrhea of “rice water stool” with loss of water and electrolytes.
The fluid secreted is isotonic with plasma with a relatively higher concentration of sodium, potassium and bicarbonate and lower concentration of chloride.