Action of antibiotics

• β-lactam antibiotics inhibit the transpeptidase (similar structure to D-alanyl D-alanine in the peptide chain)

  via competitive inhibition; irreversible binding
• Quinolones:

  • Nalidixic acid
  • Ciprofloxacin
  • Moxifloxacin
  • DNA gyrase inhibitors
• Quinolones: Mechanism of Action

  • Quinolone antibiotics interfere with changes in DNA supercoiling by binding to DNA gyrase (topoisomerase II [1st and 2nd generation Qs] or topoisomerase IV [3rd and 4th generation Qs])
  • DNA gyrase is important for controlled unwinding of DNA during replication.
  • Quinolones prevent controlled unwinding of supercoiled DNA.
  • This leads to the formation of double-stranded DNA breaks and cell death
• The Macrolides:

  Erythromycin

  • Macrocyclic lactone ring
  • Mostly Gram+
  • Protein synthesis inhibitors
  • Reversible binding to the P site on 50S ribosomal subunit
  • Bacteriostatic
  • Disruption of proteome leading to cell death
• The Aminoglycosides:

  • •Bactericidal (aerobic Gram-)
  • Protein synthesis inhibitors
  • Bind to the aminoacyl site of 16S rRNA in 30S subunit of the ribosome (irreversible)
  • Cause mis-incorporation of amino acids into elongating peptides
  • Incorporation of misfolded membrane proteins into the cell envelope leads to increased drug uptake
  • Increase in ribosome binding
  • Cell death
• The Tetracyclines:

  • Broad spectrum (better against Gram+)
  • Bacteriostatic
  • Protein synthesis inhibitors
  • Inhibit binding of aminoacyl-tRNA to mRNA-ribosome complex in the A site of 30S robosomal subunit
  • Stall protein synthesis
  • Reversible binding
  • Cause disruption to proteome leading to bacteriostasis
  • Also bind matrix metalloproteinases (useful!)
• What is the target of Macrolide antibiotics?

  Protein synthesis
•  What is the target of Quinolone antibiotics?

  Nucleic acids
•  What is the target of Tetracycline antibiotics?

  protein synthesis