Mechanism of action of antibiotics – Part I

Mechanism of action of antibiotics – Part I

Penicillin:

Penicillin kills susceptible bacteria by specifically inhibiting the transpeptidase that catalyzes the final step in cell wall biosynthesis, the cross-linking of peptidoglycan. Penicillin is a structural analog of the acyl-D-alanyl-D-alanine terminus of the pentapeptide side chains of nascent peptidoglycan. The membranes of many species of bacteria contain one major and several minor proteins (penicillin binding protein-PBP) which bind penicillin covalently. These proteins specifically catalyze the penicillin-sensitive hydrolysis of COOH-terminal D-alanine from the peptide chain of cell wall-related substrates. Hence, these enzymes have been given the name D-alanine carboxypeptidase (CPase). Penicillin covalently binds to CPase via an ester linkage to serine 36 which is relatively rapidly hydrolyzed. Penicillin acylates the active site of enzymes involved in cell wall biosynthesis. Thus formation of a complete cell wall is blocked, leading to osmotic lysis.

Chloramphenicol:

Chloramphenicol is a bacteriostatic antibiotic inhibits protein synthesis in bacteria. Chloramphenicol enters the bacteria by an energy-dependent process. It binds to 23S rRNA on the 50S ribosomal subunit to inhibit (competitive inhibition) the peptidyl transferase reaction. Binding of Chloramphenicol induces conformational change in the ribosome, which slows or even inhibits the incorporation of the aminoacyl tRNA and in turn the transpeptidation reaction and block protein chain elongation. It specifically binds to A2451 and A2452 residues in the 23S rRNA of the 50S ribosomal subunit, preventing peptide bond formation.

Tetracycline:

Tetracyclines are bacteriostatic and time dependent antibiotics. They enter gram negative bacteria by passive diffusion through the porin channels and gram positive bacteria and other organisms by active transport. After entering the cell, tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome, blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex. This inhibits addition of amino acids to the growing peptide. tetracyclines are responsible for the selective toxicity to the microbes because the carrier involved in the active transport of Tetracycline is absent in the mammalian cells and also tetracyclines do not bind to mammalian 60S or 40S ribosomes.