UPSC MainsMEDICAL-SCIENCE-PAPER-I202410 Marks
Q12.

Which antibiotics and toxins inhibit protein synthesis in prokaryotes and eukaryotes? Briefly explain the mechanism of action of each of them.

How to Approach

This question requires a detailed understanding of how various antibiotics and toxins interfere with protein synthesis, differentiating between prokaryotic and eukaryotic mechanisms. The answer should be structured by first categorizing the inhibitors (antibiotics & toxins), then detailing their specific mechanisms of action, and finally highlighting differences in their effects on prokaryotes vs. eukaryotes. Focus on ribosomal targets and specific steps in translation. A tabular format will be helpful for comparison.

Model Answer

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Introduction

Protein synthesis is a fundamental process in all living organisms, but significant differences exist between prokaryotic and eukaryotic systems, making it a prime target for antimicrobial agents. Antibiotics and certain toxins exploit these differences to selectively inhibit protein synthesis, leading to cell death or growth inhibition. Understanding these mechanisms is crucial for developing effective therapies and combating antibiotic resistance. This answer will detail the antibiotics and toxins that inhibit protein synthesis in both prokaryotes and eukaryotes, along with a brief explanation of their respective mechanisms of action.

Antibiotics Inhibiting Prokaryotic Protein Synthesis

Prokaryotic protein synthesis is a major target for antibiotics due to the structural differences between prokaryotic (70S) and eukaryotic (80S) ribosomes. Several classes of antibiotics interfere with different stages of this process.

1. Aminoglycosides (e.g., Streptomycin, Gentamicin)

  • Mechanism: Bind to the 30S ribosomal subunit, causing misreading of mRNA and premature termination of translation. They also interfere with the initiation complex formation.
  • Prokaryotes: Highly effective due to the higher affinity for the 70S ribosome.
  • Eukaryotes: Lower affinity for the 80S ribosome, resulting in less toxicity, but some mitochondrial toxicity can occur.

2. Tetracyclines (e.g., Doxycycline, Minocycline)

  • Mechanism: Bind to the 30S ribosomal subunit, preventing the attachment of aminoacyl-tRNA to the A-site of the ribosome, thus blocking the addition of amino acids to the growing polypeptide chain.
  • Prokaryotes: Effectively inhibit bacterial growth.
  • Eukaryotes: Can inhibit protein synthesis in eukaryotic cells, but uptake is generally limited, reducing toxicity.

3. Macrolides (e.g., Erythromycin, Azithromycin)

  • Mechanism: Bind to the 23S rRNA of the 50S ribosomal subunit, blocking the translocation step of protein synthesis – the movement of the ribosome along the mRNA.
  • Prokaryotes: Widely used against bacterial infections.
  • Eukaryotes: Can bind to the 50S subunit of eukaryotic ribosomes, but with lower affinity, leading to some side effects.

4. Chloramphenicol

  • Mechanism: Binds to the 23S rRNA of the 50S ribosomal subunit, inhibiting peptidyl transferase activity, preventing peptide bond formation.
  • Prokaryotes: Broad-spectrum antibiotic.
  • Eukaryotes: Can inhibit mitochondrial protein synthesis (as mitochondria have 70S-like ribosomes), leading to bone marrow suppression.

5. Lincosamides (e.g., Clindamycin)

  • Mechanism: Similar to macrolides, bind to the 23S rRNA of the 50S ribosomal subunit, inhibiting translocation.
  • Prokaryotes: Effective against many Gram-positive bacteria.
  • Eukaryotes: Similar to macrolides, lower affinity for eukaryotic ribosomes.

Toxins Inhibiting Protein Synthesis

1. Diphtheria Toxin

  • Mechanism: Inhibits elongation factor 2 (EF-2), a GTP-dependent factor essential for translocation. This prevents the movement of tRNA from the A-site to the P-site.
  • Prokaryotes & Eukaryotes: Affects both, but its primary effect in humans is on eukaryotic cells.

2. Shiga Toxin (produced by *Shigella dysenteriae*)

  • Mechanism: Cleaves 28S rRNA in the 60S ribosomal subunit, inhibiting protein synthesis.
  • Prokaryotes & Eukaryotes: Affects both, but its primary effect in humans is on eukaryotic cells, causing hemorrhagic colitis and hemolytic uremic syndrome.

Comparison Table

Inhibitor Target Mechanism Prokaryotes Eukaryotes
Streptomycin 30S Ribosome Misreading of mRNA High Low (some mitochondrial toxicity)
Tetracycline 30S Ribosome Blocks tRNA attachment High Low
Erythromycin 50S Ribosome Blocks translocation High Low
Chloramphenicol 50S Ribosome Inhibits peptidyl transferase High Moderate (mitochondrial toxicity)
Diphtheria Toxin EF-2 Inhibits translocation Both Primary effect on eukaryotic cells
Shiga Toxin 28S rRNA Cleaves rRNA Both Primary effect on eukaryotic cells

Conclusion

In conclusion, a diverse range of antibiotics and toxins target protein synthesis in prokaryotes and eukaryotes, exploiting structural and functional differences in their ribosomal machinery. While many antibiotics selectively target bacterial ribosomes, some exhibit toxicity towards eukaryotic cells, particularly affecting mitochondrial function. Understanding these mechanisms is vital for developing new antimicrobial strategies and minimizing adverse effects. The emergence of antibiotic resistance necessitates continuous research into novel inhibitors of protein synthesis.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Translocation
The process during protein synthesis where the ribosome moves along the mRNA molecule, shifting the tRNA molecules from one site to another on the ribosome.

Key Statistics

Antibiotic resistance is a growing global health threat. The World Health Organization (WHO) estimates that 700,000 deaths globally are attributed to antimicrobial-resistant infections each year.

Source: World Health Organization (WHO), 2024 (Knowledge Cutoff: Jan 2024)

According to the CDC, at least 2.8 million infections and 35,000 deaths occur in the United States each year due to antibiotic-resistant bacteria.

Source: Centers for Disease Control and Prevention (CDC), 2023 (Knowledge Cutoff: Jan 2024)

Examples

MRSA Infection

Methicillin-resistant *Staphylococcus aureus* (MRSA) is a bacterium that has developed resistance to many antibiotics, including methicillin and other beta-lactams. This resistance is often due to the acquisition of the *mecA* gene, which encodes an altered penicillin-binding protein.

Frequently Asked Questions

Why are some antibiotics more toxic to eukaryotic cells than others?

The toxicity depends on the antibiotic's affinity for eukaryotic ribosomes. Some antibiotics have a lower affinity, resulting in fewer side effects. However, some can still affect mitochondrial ribosomes (which are 70S-like), leading to toxicity.

Topics Covered

BiochemistryPharmacologyProtein SynthesisAntibioticsToxins