Question

This week you have been introduced to the specific mechanisms (example: A-B toxin) that elicit the symptoms of disease in a host. Pick three of these mechanisms and describe each in a research paper. Please follow the expectations that are listed below.

• Introduction (list the three mechanisms that you have picked and provide a brief overview)

• Mechanism 1 (Describe the cellular source of the mechanism. Explain how this mechanism produces an effect inside the host. Provide an example pathogen that utilizes this mechanism).

• Mechanism 2 (Describe the cellular source of the mechanism. Explain how this mechanism produces an effect inside the host. Provide an example pathogen that utilizes this mechanism).

• Mechanism 3 (Describe the cellular source of the mechanism. Explain how this mechanism produces an effect inside the host. Provide an example pathogen that utilizes this mechanism).

Answer 1

Introduction

Three mechanisms of toxin action

1)Activation of adenylate cyclase and thereby increase in cyclic AMP and causing secretory diarrhoea. This is the mechanism of action of cholera toxin

2)Inhibition of elongation factor 2 and thus inhibit protein synthesis. This is the mechanism of action of diphtheria toxin

3)Inhibit the release of acetylcholine from neurons and cause flaccid paralysis.This is the mechanism of action of botulinum toxin

All these toxins are exotoxins.They are diffusible into the surrounding media .Exotoxins are very potent even in minute quantities. Of these,botulinum toxin is most potent.It is said that 39.2g of botulinum toxin is sufficient to destroy the entire mankind.They are heat labile. They can be toxoided by adding formaldehyde. Toxoids are antigenic ,but without toxicity.Hence they can be used as vaccines.

Mechanism 1

Cholera toxin

This is produced by Vibrio cholerae.The gene encoding cholera toxin is part of the pathogenicity island of the bacteria.It is encoded by the genome of a filamentous bacteriophage that is integrated as prophage into the bacterial chromosome.The organism once established in the human small intestinal epithelium,it produce the exotoxin.It has two fragment- fragment A and B.Fragment B has five subunits and is the binding fragment.It binds to the GM1 ganglioside receptors present on the surface of intestinal epithelium and internalise fragment A.Fragment A then splits into A1and A2.A2 helps in binding fragment B to A.A1 is the active fragment. It causes ADP ribosylation of G protein.Thus upregulation of activity of adenylate cyclase.This causes intracellular accumulation of cyclic AMP.This causes inhibition of absorptive sodium transport and activation of secretory chloride transport system. Thus sodium chloride accumulate in the intestinal lumen.To maintain osmolality,water also moves into the lumen.This causes watery diarrhea.

Mechanism 2

2)Diphtheria toxin- produced by Corynebacterium diphtheriae

The gene responsible for the production of this toxin is also coded by a bacteriophage called beta corynephage carrying the tox gene.This also has two fragments -A and B.B is the binding fragment which blinds to the epidermal growth factor receptor on various cells and internalise fragment A.Fragment A is the active fragment which cause ADP ribosylation of elongation factor 2 and inhibit it.Thus it inhibit the translation step of protein synthesis. This is responsible for production of pseudomembranes(by necrosis of epithelium)

Mechanism 3

Botulinum toxin- produced by Clostridium botulinum

It is produced by the bacteria and not secreted until bacteria undergo autolysis.Toxin enters blood stream once bacteria enters body.Through blood it reach peripheral cholinergic nerve endings. There it binds to acetyl choline receptors ,thus preventing release of acetyl choline and cause flaccid paralysis