Untitled Quiz

Introduction to Antimicrobial

• The lecture is about antimicrobial agents.
• Learning outcomes include explaining terms like selective toxicity, bactericidal, bacteriostatic, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC).
• Classify antibiotics based on their mechanism of action on bacteria, with suitable examples.
• Describe how organisms develop drug resistance.

History of Antimicrobial Agents

• Ancient Egyptians used moldy bread to treat wounds.
• 1910: Gerhard Domagk & Ernest Fourneau discovered prontosil (a red dye containing sulfonamides), which inhibits the growth of Gram-positive bacteria.
• 1910: Paul Ehrlich described the mechanism of chemical substances binding to tissues.
• 1928: Alexander Fleming discovered Penicillium mold to inhibit bacterial growth.
• 1940: Ernst Chain & Howard Florey mass-produced penicillin.
• 1944: Penicillin played a significant role in healing during World War II.
• "Doctors could now cure disease, and this was astonishing, most of all to the doctors themselves." - Lewis Thomas

Definitions

• Selective toxicity: The ability of an antimicrobial agent to attack the target microorganism without causing significant damage to the host. Penicillin - toxic dosage level vs therapeutic dosage level.
• Bacteriostatic: Antimicrobial activity that inhibits growth but does not kill the organisms.
• Bactericidal: Antimicrobial activity that not only inhibits growth, but is lethal to bacteria.
• Minimum Inhibitory Concentration (MIC): The lowest concentration of antimicrobial agent that inhibits visible in-vitro growth of microorganisms (expressed as mg/L or µg/µL).
• Minimum Bactericidal Concentration (MBC): The lowest concentration of antibiotics that kills 99.9% of the inoculum.

Mechanism of Action of Antibiotics

• Inhibition of cell wall synthesis: Penicillin, bacitracin, cephalosporin, vancomycin.

  • Peptidoglycan is a key component of bacterial cell walls.
  • Some antibiotics contain a β-lactam ring that interferes with the enzymes that cross-link peptidoglycans, disrupting cell wall synthesis. Examples include penicillins and cephalosporins.
  • Vancomycin binds directly to the terminal amino acids of the peptide side chains.

• Disruption of cell membrane function: Polymyxin.

  • Interfere with bacterial cell membrane permeability.

• Inhibition of protein synthesis: Tetracycline, erythromycin, streptomycin, chloramphenicol.

  • Aminoglycosides, like streptomycin, act on the 30S portion of bacterial ribosomes, interfering with accurate mRNA reading during translation.
  • Chloramphenicol and erythromycin target the 50S portion, inhibiting polypeptide formation.

• Inhibition of nucleic acid synthesis: Quinolones, rifamycins.

  • Quinolones inhibit DNA topoisomerases and DNA gyrase, interfering with DNA replication.
  • Rifampin blocks RNA polymerase, interfering with RNA synthesis.

• Folate inhibitors: Sulfonamides, trimethoprim.

• Interferes with folic acid synthesis, a crucial step for nucleic acid synthesis within bacteria.

Antimicrobial Resistance

• Mechanisms of resistance: alternation of membrane permeability, alterations of antimicrobial targets, inactivation of the antimicrobial agent.
• Alteration of membrane permeability: Change in the membrane transport system that prevents antimicrobial agents from entering the cell. Ex: Pseudomonas aeruginosa resistance to imipenem.
• Altered antimicrobial targets: Mutations or enzymatic modifications create proteins (modified targets) with reduced or no affinity for the antibiotics. This can affect bacterial cell wall components (e.g., transpeptidases): Examples include:
  • Methicillin-resistant Staphylococcus aureus (MRSA).
  • Vancomycin-resistant enterococci (VRE).
• Inactivation of antimicrobial agents: Hydrolyzing or chemically modifying antibiotics, preventing their ability to bind to their targets. Ex: Beta-lactamases inactivate penicillins.