Inhibition of protein synthesis (antibiotics and toxins)

Protein synthesis, an essential biological process for cell function and survival, can be targeted by various antibiotics and toxins. These inhibitors disrupt the translation process, leading to the cessation of protein production, which can have therapeutic or toxic effects. Here’s a detailed overview of how antibiotics and toxins inhibit protein synthesis:

1. Antibiotics

Antibiotics are substances that inhibit the growth of or kill bacteria. Many antibiotics target the bacterial ribosome, which is different enough from eukaryotic ribosomes to allow selective inhibition of bacterial protein synthesis without harming the host.

Targeting the Ribosomal Subunits

1. 30S Ribosomal Subunit Inhibitors:

   • Streptomycin: Binds to the 30S subunit and causes misreading of mRNA, leading to faulty proteins.

   • Tetracyclines: Block the attachment of aminoacyl-tRNA to the A site on the 30S subunit, preventing the addition of new amino acids to the growing polypeptide chain.

   • Gentamicin is bactericidal and is a broad spectrum antibiotic (except against streptococci and anaerobic bacteria). Its mechanism of action involves inhibition of bacterial protein synthesis by binding to 30S ribosomes. 

   • Kanamycin (KAN) is an aminoglycoside  antibiotic having the same mode of action as streptomycin (STR); it inhibits protein synthesis by tightly binding to the conserved A site of 16S rRNA in the 30S ribosomal subunit. 

2. 50S Ribosomal Subunit Inhibitors:

   • Chloramphenicol: It inhibits microbial protein synthesis by binding to the 50 S subunit of the 70 S ribosome and inhibiting the action of peptidyl transferase, thus preventing peptide bond formation 

   • Erythromycin: Binds to the 50S subunit and blocks the exit tunnel, impeding the movement of the growing polypeptide.

Other Inhibitory Mechanisms

1. Rifampicin: Binds to bacterial RNA polymerase, inhibiting RNA synthesis, indirectly affecting protein synthesis by preventing mRNA production.

2. Fusidic Acid: Fusidic acid inhibits protein synthesis by binding EF-G-GDP, which results in the inhibition of both peptide translocation and ribosome disassembly.  

2. Toxins

Toxins are harmful substances produced by organisms such as bacteria, plants, or animals. Some toxins specifically target and disrupt protein synthesis, leading to cell death or dysfunction.

Ribosome-Inactivating Toxins

1. Diphtheria Toxin:

   • Produced by Corynebacterium diphtheriae.

   • Inhibits eukaryotic protein synthesis by ADP-ribosylating elongation factor 2 (eEF2), preventing ribosome translocation and elongation of the polypeptide chain.

   • This toxin effectively halts protein synthesis, leading to cell death.

2. Ricin :

   • A plant toxin derived from the castor bean (Ricinus communis).

   • Depurinates a specific adenine residue in the 28S rRNA of the 60S subunit in eukaryotic ribosomes, inactivating the ribosome and blocking protein synthesis.

   • Extremely potent, even minute amounts can be lethal by inhibiting critical protein synthesis in cells.

Conclusion

The inhibition of protein synthesis by antibiotics and toxins is a powerful mechanism to control or eradicate bacteria and, in some cases, target cancer cells or other pathogens. Antibiotics leverage the differences between prokaryotic and eukaryotic ribosomes for selective inhibition, while toxins often target crucial components of the translation machinery in eukaryotic cells. Understanding these mechanisms is essential for developing new antimicrobial agents and for studying the effects of toxins on cellular processes.