What antimicrobials actually do
Antimicrobials are chemicals that kill microorganisms or stop them from multiplying, while leaving human cells largely unharmed. They achieve this selectivity by attacking structures and processes that microbes have and we do not:
- Cell wall synthesis — penicillins, cephalosporins and other beta-lactams block the machinery bacteria use to build their protective wall.
- Protein production — tetracyclines, macrolides and aminoglycosides jam the bacterial ribosome, which differs from ours.
- DNA copying and repair — fluoroquinolones trap the enzymes bacteria need to replicate their DNA.
- Metabolism — sulfonamides starve bacteria of folate, a vitamin they must make themselves.
Antivirals, antifungals and antiparasitics work on analogous principles against their own targets. The word antibiotic refers specifically to drugs against bacteria — the part of the AMR problem this site focuses on most, because it carries the largest burden of death.
Resistance is natural selection at high speed
Bacteria divide as quickly as every 20 minutes, and every division carries a small chance of a random mutation. In a population of billions, some cells will, purely by chance, carry a change that makes an antibiotic slightly less effective against them. When that antibiotic is used, susceptible cells die and the resistant few survive, multiply, and inherit the population.
Three points follow from this, and they explain almost everything else on this site:
- Resistance is ancient and inevitable. Many antibiotics originally come from soil microbes that have been waging chemical warfare on each other for millions of years — and evolving defences just as long. Resistance genes have been found in 30,000-year-old permafrost.
- Every use of an antimicrobial applies selection pressure. Appropriate use buys enormous benefit for that pressure; unnecessary use breeds resistance and buys nothing.
- Resistance anywhere becomes resistance everywhere. Resistant microbes and their genes travel with people, animals, food, water and trade. A resistance gene that emerged in one country has repeatedly turned up on other continents within a few years.
The molecular tricks bacteria use
Bacteria have evolved four main strategies to defeat antibiotics:
| Strategy | How it works | Example |
|---|---|---|
| Destroy the drug | Enzymes chop up or chemically disable the antibiotic before it can act. | Beta-lactamases (including ESBLs and carbapenemases such as NDM-1 and KPC) destroy penicillins, cephalosporins and even carbapenems — our drugs of last resort. |
| Change the target | A mutation alters the protein the drug binds to, so the drug no longer fits. | MRSA makes an altered cell-wall-building protein (PBP2a) that methicillin and related drugs cannot block. |
| Pump it out | Efflux pumps eject the antibiotic from the cell faster than it can enter. | Pseudomonas aeruginosa uses multiple pumps that expel many drug classes at once. |
| Keep it out | The cell reduces or closes the entry channels (porins) in its outer membrane. | Carbapenem resistance in some Enterobacterales combines porin loss with enzyme production. |
On top of these, many bacteria form biofilms — slimy, cooperative communities on surfaces such as catheters, implants and lung tissue — inside which they can tolerate antibiotic concentrations hundreds of times higher than free-floating cells can.
Horizontal gene transfer: resistance is contagious
If resistance only spread from parent cell to daughter cell, it would move slowly. The real accelerant is that bacteria can share genes sideways, even across species, in three ways:
- Conjugation — two cells connect and one copies a plasmid (a small ring of DNA, often loaded with several resistance genes) to the other. This is the dominant route.
- Transformation — a cell scavenges naked DNA released by dead neighbours.
- Transduction — viruses that infect bacteria (bacteriophages) accidentally carry genes from one host to the next.
Because a single plasmid can carry resistance to five or six drug classes, one transfer event can turn an ordinary microbe into a multidrug-resistant one overnight. This is how genes like NDM-1 (a carbapenemase first identified in 2008) and mcr-1 (which defeats colistin, a last-line antibiotic, reported in 2015) spread worldwide within a few years of being detected.
Degrees of resistance
- MDR (multidrug-resistant) — resistant to at least one drug in three or more antibiotic classes.
- XDR (extensively drug-resistant) — susceptible to only one or two remaining classes.
- PDR (pandrug-resistant) — resistant to every available agent. Rare, but rising: untreatable infections are already being reported.
The key takeaway
People do not become resistant to antibiotics — bacteria do. Resistance is a property of the microbe, driven by selection pressure from every dose used anywhere in humans, animals or the environment, and spread by mobile genes that ignore species boundaries and national borders.
Sources for this page
- WHO fact sheet, “Antimicrobial resistance” — who.int/news-room/fact-sheets/detail/antimicrobial-resistance
- CDC, “About Antimicrobial Resistance / How Antimicrobial Resistance Happens” — cdc.gov/antimicrobial-resistance
- “Antibiotic Use in Livestock Farming: A Driver of Multidrug Resistance?” (mechanisms and horizontal gene transfer), PMC, 2025 — pmc.ncbi.nlm.nih.gov/articles/PMC12029767/
- D'Costa et al., “Antibiotic resistance is ancient”, Nature, 2011 (permafrost resistance genes).