The one idea behind every antibiotic
When you take a painkiller, you want it to act on your own cells. An antibiotic is the opposite: you want it to poison the bacteria living inside you while leaving your own tissues unharmed. That is only possible because of [[pharm-selective-toxicity|selective toxicity]] — the drug attacks a structure or process the microbe has but you don't, or one that is different enough to be hit safely. This single principle, named by Paul Ehrlich a century ago, is why we have safe antimicrobials at all.
The best targets are the ones humans simply lack. Bacteria have a rigid cell wall; we don't. Bacteria build proteins on ribosomes that differ from ours; we have our own version. The bigger the gap between microbe and host, the safer the drug — and the wider its therapeutic index.
Five places a drug can attack a bacterium
Most antibacterials work through one of a handful of mechanisms. Knowing the target tells you a lot about what a class can do and whom it might harm.
- Cell wall — bacteria are wrapped in peptidoglycan; humans have no cell wall, so this is the safest target (beta-lactams, vancomycin).
- Protein synthesis — bacterial ribosomes (30S and 50S) differ from ours, so drugs can jam them selectively (aminoglycosides, macrolides, tetracyclines).
- DNA/RNA — enzymes like DNA gyrase have no human equivalent (fluoroquinolones; rifampicin blocks bacterial RNA polymerase).
- Folate pathway — bacteria must make their own folate; we eat ours, so blocking synthesis (sulfonamides, trimethoprim) starves them, not us.
- Cell membrane — disrupting it is potent but risky, because our membranes are similar; reserved for last-line agents (polymyxins).
Notice how the safest classes (wall, folate) hit things humans simply don't have, while the harshest (membrane) hit something we share. Selectivity is never perfect, though — even cell-wall drugs can trigger a hypersensitivity reaction, and overuse of any of them speeds up antimicrobial resistance, the theme we return to in guide 4.