Introduction to Antibiotics

Antibiotics are chemical compounds that inhibit bacterial growth by interfering with bacterial-specific enzymes or processes. Their selective toxicity relies on targeting structures absent in human cells or sufficiently different in prokaryotic cells to produce much greater toxicity to bacteria. The three principal target categories are cell wall synthesis, protein synthesis, and nucleic acid synthesis.

Beta-lactams are the most important class targeting cell wall synthesis. They share a common beta-lactam ring and bind irreversibly to penicillin-binding proteins (transpeptidases) via their serine residue, inhibiting the cross-linking of peptidoglycan peptide side chains. This is most effective against actively growing bacteria. Subclasses include penicillins, cephalosporins, monobactams, and carbapenems (the broadest-spectrum beta-lactam). Glycopeptides such as vancomycin act by binding to the D-alanine-D-alanine terminus of peptidoglycan peptide chains, preventing transpeptidase binding, but are unable to penetrate the outer membrane of gram-negative bacteria due to their large molecular size.

Protein synthesis inhibitors bind to bacterial ribosomes (30S or 50S subunits) with much higher affinity than eukaryotic ribosomes. Aminoglycosides (e.g., gentamicin) and tetracyclines target the 30S subunit; macrolides (e.g., clarithromycin), lincosamides (e.g., clindamycin), and oxazolidinones (e.g., linezolid) target the 50S subunit.

Nucleic acid synthesis inhibitors include sulfonamides (inhibit dihydropteroate synthase, the first step of tetrahydrofolic acid synthesis) and trimethoprim (inhibits dihydrofolate reductase, the second step), often combined as cotrimoxazole for broad-spectrum coverage. Fluoroquinolones (e.g., ciprofloxacin) inhibit bacterial type II topoisomerases (DNA gyrase in gram-negatives, topoisomerase IV in gram-positives). Rifampicin targets RNA polymerase but is never used as monotherapy due to rapid resistance development. Metronidazole, a prodrug selectively activated in anaerobes and protozoa, disrupts DNA structure and inhibits replication.