Antibiotics

Why Antibiotics Matter

  • Essential for medical treatments (e.g., surgeries, cancer treatments).

  • Influence life expectancy significantly.

Antimicrobial Resistance (AMR) Overview

  • Current low estimate of AMR deaths: 700,000/year.

  • Prediction for 2050: 10 million deaths/year if not addressed.

History of Antibiotics

  • First synthetic antimicrobial: Salvarsan (1910).

  • Sulfa drugs were the first effective broad-spectrum antibiotics.

  • Penicillin discovered in 1928.

  • Actinomycetes are key sources of natural antibiotics.

Antibiotic Discovery Challenges

  • Last major class discovered ~1987.

  • Factors: Cost ($1 billion to market), diminishing investment, and rising resistance.

Antibiotic Effects

  • Bactericidal: Kill bacteria.

  • Bacteriostatic: Inhibit growth.

  • Measurement: Optical Density (OD) and Colony-Forming Units (CFU/ml).

Antibiotic Mechanisms

  • β-lactams: Inhibit cell wall synthesis, effective against dividing cells.

  • Aminoglycosides: Bind 30S ribosomal subunit, disrupt protein synthesis, bactericidal effect.

  • Macrolides: Bind 50S subunit, inhibit protein elongation, generally bacteriostatic.

  • Fluoroquinolones: Inhibit topoisomerases, cause lethal DNA breaks, bactericidal.

Measuring Antibiotic Effectiveness

  • MIC (Minimum Inhibitory Concentration): lowest concentration preventing growth.

  • Requires consideration of multiple factors for clinical decisions (e.g., pharmacokinetics, resistance).

Future Directions in Antibiotic Discovery

  • Exploration of new natural products, genome mining, drug repurposing.

  • Technological advances like AI for drug design and synthesis.

Alternatives to Antibiotics

  • Phage therapy, predatory bacteria, microbiome modulation, and vaccines.