Antimicrobials & Resistance

Antibiotic Targets and Selective Toxicity

• Beta-lactams (penicillins) block peptidoglycan cross-linking — humans have no cell wall. Aminoglycosides bind the 30S ribosomal subunit; macrolides like erythromycin bind the 50S — safe because human ribosomes are 80S. Fluoroquinolones inhibit DNA gyrase; sulfonamides block folate synthesis.
• A drug is clinically useful when it hits a structure the pathogen has and the host lacks: peptidoglycan, the 70S ribosome, gyrase, or folate synthesis.
• Antibiotics do nothing against viruses, which replicate with host machinery; antibiotics also work best during log-phase growth, when division-linked targets are active.

Resistance Mechanisms

• Enzymatic degradation: beta-lactamase hydrolyzes the beta-lactam ring before the drug can act.
• Target modification: an altered ribosomal binding site defeats macrolides.
• Efflux pumps: membrane transporters expel tetracycline faster than it enters.
• Decreased permeability: porin mutations shut the door on drug entry.
• Resistance genes travel on plasmids by conjugation, so a single transfer can carry several mechanisms at once and cross species lines.

Key Takeaways

• Match each antibiotic class to its molecular target.
• Selective toxicity rests on prokaryote-only structures.
• Four resistance strategies: destroy, modify, pump out, or exclude the drug.
• Plasmid-borne resistance spreads horizontally and in multidrug bundles.