Question
Explain mechanism of action of the toxins produced by the following pathogens in human body ;
A. Corynebacterium diphteriae,
A. Corynebacterium diphteriae,
Answers
GPT-4o mini
Corynebacterium diphtheriae is the bacterium responsible for diphtheria, an acute inflammatory disease primarily affecting the upper respiratory tract. The pathogenicity of C. diphtheriae is largely due to the production of diphtheria toxin, which is responsible for the clinical manifestation of the disease. Here’s the mechanism of action of this toxin:
### Diphtheria Toxin Mechanism of Action
1. **Production and Activation**:
- Diphtheria toxin is an exotoxin produced by C. diphtheriae. The toxin is encoded by a bacteriophage that integrates into the bacterial genome, making the strain pathogenic.
- The toxin is initially produced as a single polypeptide chain that is then proteolytically cleaved into two fragments: Fragment A (the active enzyme) and Fragment B (the binding component).
2. **Receptor Binding**:
- Fragment B (B chain) has a high affinity for the heparin-binding epidermal growth factor (HB-EGF) receptor on the surface of human cells, particularly epithelial cells, cardiac muscle cells, and neurons.
- The binding of Fragment B allows the toxin to be internalized into the cell through receptor-mediated endocytosis.
3. **Endosomal Escape**:
- Once inside the cell, the acidic environment of endosomes triggers a conformational change in the toxin. This change facilitates the translocation of Fragment A (the active part of the toxin) from the endosome into the cytoplasm of the host cell.
4. **Inhibition of Protein Synthesis**:
- Fragment A possesses enzymatic activity that modifies elongation factor 2 (EF-2) through ADP-ribosylation. EF-2 is essential for protein synthesis as it is involved in the translocation step of the elongation cycle in translation.
- The specific modification by diphtheria toxin prevents EF-2 from functioning effectively, leading to inhibition of protein synthesis within the host cell.
5. **Cellular Effects**:
- As a result of inhibited protein synthesis, affected cells suffer cytotoxic effects, leading to cell death and tissue damage.
- This contributes to the characteristic formation of a thick pseudomembrane in the throat, which can obstruct airways and lead to serious respiratory complications.
- Additionally, systemic effects can occur, affecting the heart and nervous system, leading to complications such as myocarditis and peripheral neuropathy.
### Summary
The mechanism of action of the diphtheria toxin produced by Corynebacterium diphtheriae involves receptor-mediated endocytosis, release of the active component into the cytoplasm, and subsequent inhibition of protein synthesis by modifying elongation factor 2. This results in cellular damage and the clinical symptoms associated with diphtheria.
### Diphtheria Toxin Mechanism of Action
1. **Production and Activation**:
- Diphtheria toxin is an exotoxin produced by C. diphtheriae. The toxin is encoded by a bacteriophage that integrates into the bacterial genome, making the strain pathogenic.
- The toxin is initially produced as a single polypeptide chain that is then proteolytically cleaved into two fragments: Fragment A (the active enzyme) and Fragment B (the binding component).
2. **Receptor Binding**:
- Fragment B (B chain) has a high affinity for the heparin-binding epidermal growth factor (HB-EGF) receptor on the surface of human cells, particularly epithelial cells, cardiac muscle cells, and neurons.
- The binding of Fragment B allows the toxin to be internalized into the cell through receptor-mediated endocytosis.
3. **Endosomal Escape**:
- Once inside the cell, the acidic environment of endosomes triggers a conformational change in the toxin. This change facilitates the translocation of Fragment A (the active part of the toxin) from the endosome into the cytoplasm of the host cell.
4. **Inhibition of Protein Synthesis**:
- Fragment A possesses enzymatic activity that modifies elongation factor 2 (EF-2) through ADP-ribosylation. EF-2 is essential for protein synthesis as it is involved in the translocation step of the elongation cycle in translation.
- The specific modification by diphtheria toxin prevents EF-2 from functioning effectively, leading to inhibition of protein synthesis within the host cell.
5. **Cellular Effects**:
- As a result of inhibited protein synthesis, affected cells suffer cytotoxic effects, leading to cell death and tissue damage.
- This contributes to the characteristic formation of a thick pseudomembrane in the throat, which can obstruct airways and lead to serious respiratory complications.
- Additionally, systemic effects can occur, affecting the heart and nervous system, leading to complications such as myocarditis and peripheral neuropathy.
### Summary
The mechanism of action of the diphtheria toxin produced by Corynebacterium diphtheriae involves receptor-mediated endocytosis, release of the active component into the cytoplasm, and subsequent inhibition of protein synthesis by modifying elongation factor 2. This results in cellular damage and the clinical symptoms associated with diphtheria.