Mechanisms of action of antibiotics
Also known as: antibiotic mechanism of action
Antibiotics kill or inhibit bacteria by targeting structures and processes unique to bacterial cells — chiefly cell wall synthesis, protein synthesis, nucleic acid synthesis, folate metabolism, and cell membrane integrity.
Antibiotics work through selective toxicity: they attack structures or enzymes that bacteria have and human cells lack, or that differ enough between the two to be targeted safely. Grouping drugs by mechanism of action is the standard way to organize antimicrobial pharmacology.
Cell wall synthesis inhibitors are the largest group. Beta-lactams — penicillins, cephalosporins, carbapenems, and monobactams — bind penicillin-binding proteins and block peptidoglycan cross-linking, while vancomycin binds the D-Ala-D-Ala terminus of cell wall precursors. Protein synthesis inhibitors exploit the bacterial 70S ribosome: aminoglycosides and tetracyclines act on the 30S subunit, while macrolides, chloramphenicol, clindamycin, and linezolid act on the 50S subunit ("buy AT 30, CELL at 50").
Nucleic acid synthesis inhibitors include the fluoroquinolones, which block DNA gyrase and topoisomerase IV, and rifampin, which inhibits bacterial RNA polymerase. Sulfonamides and trimethoprim block sequential steps in folate synthesis, starving bacteria of the precursors needed for DNA and RNA. Finally, membrane-active agents such as daptomycin and the polymyxins disrupt the bacterial cell membrane itself. Drugs are also classed as bactericidal (killing bacteria, like beta-lactams and aminoglycosides) or bacteriostatic (halting growth, like tetracyclines and macrolides).
USMLE Step 1 tests antibiotic mechanisms relentlessly in its microbiology and pharmacology sections. High-yield tasks include matching each drug class to its target, distinguishing 30S from 50S ribosomal inhibitors, and pairing mechanisms with the resistance strategies bacteria evolve against them.
Key takeaways
- Antibiotics achieve selective toxicity by targeting structures unique to bacteria.
- Beta-lactams and vancomycin block cell wall (peptidoglycan) synthesis.
- Protein synthesis inhibitors split by ribosomal target: aminoglycosides and tetracyclines at 30S; macrolides, chloramphenicol, clindamycin, and linezolid at 50S.
- Fluoroquinolones inhibit DNA gyrase, rifampin inhibits RNA polymerase, and sulfonamides/trimethoprim block folate synthesis.
- USMLE Step 1 heavily tests matching drug classes to mechanisms and to resistance patterns.