The short answer
Antibiotic resistance is evolution happening fast enough to watch.
When an antibiotic is used, most of the target bacteria die. A few may survive because they carry an inherited difference that protects them. Those survivors multiply. The next generation contains more resistant bacteria than the last. Repeat that enough times and a drug that used to work stops working.
Key idea: The drug does not create resistance. It removes the bacteria that are not resistant, so the ones that are resistant take over.
What antibiotics do
Antibiotics are medicines that kill bacteria or stop them from growing. Different antibiotics attack different parts of a bacterial cell. Penicillin, for example, stops bacteria from building their cell wall properly, so the cells burst. Other drugs jam the machinery bacteria use to make proteins or copy their DNA.
Human cells are built differently, which is why a good antibiotic can harm bacteria while mostly leaving you alone.
Antibiotics do nothing to viruses. Colds, most sore throats, and flu are caused by viruses, so antibiotics cannot help with them. Viruses evolve too, but in their own way. You can read about that in virus evolution and vaccines.
A short history: resistance arrived almost at once
Alexander Fleming noticed in 1928 that a mould called Penicillium killed bacteria growing near it on a lab dish. It took more than a decade before other scientists, led by Howard Florey and Ernst Chain, worked out how to purify penicillin and make it in large amounts. Mass production took off during the Second World War in the 1940s.
Resistance was spotted even before penicillin was widely used. In 1940, Edward Abraham and Ernst Chain reported that some bacteria make an enzyme that breaks penicillin down.
Fleming shared the Nobel Prize in 1945. In his Nobel lecture he warned that people who took too little penicillin could expose their bacteria to doses that did not kill them, and so make them resistant. He was right about the general danger.
The pattern then repeated with each new drug. A good example is methicillin, a penicillin-type drug introduced in Britain in 1959 to treat Staphylococcus aureus that had become resistant to penicillin. Doctors reported methicillin-resistant strains in 1961. Those strains are now known as MRSA, and they remain a major cause of hard-to-treat infections.
Resistance genes are also far older than medicine. Many antibiotics were first found in soil microbes, which use them against their neighbours. In 2011, researchers studying 30,000-year-old permafrost found bacterial DNA carrying genes for resistance to several antibiotic types. Humans did not invent resistance. We made it far more common.
How resistance evolves, step by step
Natural selection needs three things: variation, inheritance, and a difference in survival or reproduction. Bacteria under antibiotic attack have all three.
- Variation. A large bacterial population contains cells with slightly different DNA. Some differences come from mutation, copying mistakes made each time a cell divides. Others come from genes picked up from other bacteria.
- Selection. The antibiotic kills the vulnerable cells. Any cell that happens to carry a resistance trait is more likely to survive.
- Inheritance. When a bacterium divides, both daughter cells inherit its DNA, including the resistance.
- Repetition. The survivors multiply. Next time the drug is used, a larger share of the population is already resistant.
That is natural selection, with no special rules.
The bacteria do not “decide” to adapt. A mutation does not appear because the cell needs it. Mutations happen all the time, mostly without effect. The drug simply sorts the population, and resistant cells are left standing.
Speed comes from numbers. Under ideal lab conditions the gut bacterium E. coli can divide about every 20 minutes. A single infection can involve billions of bacterial cells. Even if a useful mutation is rare, with that many cells and that many generations, rare things happen often.
How bacteria fight back
Resistance is not one trick. Bacteria use several different methods, and some carry more than one.
| Method | What it does | Example |
|---|---|---|
| Break the drug | An enzyme cuts the antibiotic apart before it can work | Beta-lactamase enzymes destroy penicillin-type drugs |
| Pump it out | Proteins in the cell wall pump the drug out faster than it builds up | Efflux pumps that remove tetracycline |
| Change the target | The part of the cell the drug attacks changes shape, so the drug no longer fits | MRSA builds a different cell-wall protein that methicillin cannot grab |
| Block the way in | The cell reduces the openings the drug uses to get inside | Some bacteria make fewer of the pores that let drugs enter |
Each of these is an inherited trait. Each can be favoured by selection whenever the matching drug is around.
Bacteria can share genes
This is where bacteria differ sharply from animals.
You inherit your genes from your parents, and that is it. Bacteria do that too, but they can also pass genes sideways to bacteria that are not their offspring. Biologists call this horizontal gene transfer.
The most important route uses plasmids. A plasmid is a small loop of DNA that sits apart from the bacterium’s main chromosome. Bacteria can copy a plasmid and pass it to a neighbouring cell through a thin connecting tube. Some plasmids carry several resistance genes at once.
That changes the picture. A harmless gut bacterium carrying a resistance plasmid can hand it to a dangerous one. Resistance can jump between different species. One bacterium can become resistant to several drugs in a single step.
A clear case was reported in 2015. Scientists in China found a gene called mcr-1 on a plasmid in bacteria from pigs, raw meat, and some patients. It gave resistance to colistin, an old antibiotic doctors keep as a last resort. Because the gene sits on a plasmid, it can spread between bacteria, and it has since been reported in many countries.
Watching it happen: the MEGA-plate
In 2016, Michael Baym, Roy Kishony and colleagues at Harvard published an experiment in the journal Science that made this visible.
They built a giant rectangular dish, about 60 by 120 centimetres, filled with a layer of food for bacteria. They divided it into bands. The outer bands had no antibiotic. Each band further in contained a much higher dose, ending with a central band far stronger than the dose that kills ordinary E. coli.
Then they put E. coli at the outer edges and filmed it.
The bacteria spread across the drug-free zone and stopped at the first wall of antibiotic. After a while, a mutant appeared that could survive there, and its descendants spread into the new band. Then they stopped at the next wall, until another mutant broke through.
In about 10 to 12 days, bacteria reached the central band. They could grow at roughly 1,000 times the dose of the antibiotic trimethoprim that killed their ancestors. The researchers could trace the family tree of mutants as they went.
The video is worth finding. It shows mutation and selection working together, one step after another, in real time. It is one of the clearest pieces of observed evolution there is.
How big is the problem?
Large. The most detailed global estimate so far was published in The Lancet in 2022 by a team called the Antimicrobial Resistance Collaborators. They estimated that in 2019, about 1.27 million deaths worldwide were directly caused by bacterial infections that resisted treatment. Resistant infections were involved in about 4.95 million deaths in total.
Those are estimates, and data were thin in many lower-income countries, so the true numbers are uncertain. But the scale is clear. The same study found the highest death rates in western sub-Saharan Africa.
In the United States, the CDC’s 2019 report estimated more than 2.8 million antibiotic-resistant infections each year, and more than 35,000 deaths.
Resistance also threatens things we take for granted. Surgery, cancer chemotherapy, and caring for premature babies all depend on antibiotics working when infections happen.
Why misuse and farm use matter
Every time an antibiotic is used, it applies selection. Sometimes that is worth it, because it cures a real infection. When the drug is used without a good reason, it still selects for resistance but gives nothing back.
Common forms of misuse include:
- taking antibiotics for viral illnesses such as colds and flu
- using leftover antibiotics or someone else’s pills
- buying antibiotics without a prescription where that is possible
Farming matters too. In many countries large amounts of antibiotics are given to farm animals, and in the past they were often added to feed to make animals grow faster rather than to treat disease. Resistant bacteria and resistance genes can then reach people through food, water, and contact with animals. The European Union banned antibiotics as growth promoters in 2006, and many other countries have since restricted the practice.
What about finishing the course?
For decades the standard advice was “always finish the course, even if you feel better.” The reasoning was that stopping early would let the toughest bacteria survive.
The picture is now more complicated. For several common infections, studies have found that shorter courses work as well as longer ones, and every extra day of antibiotics is another day of selection on all the other bacteria in your body. For some infections, such as tuberculosis, long and complete courses really are essential.
So the honest answer is this. The right length depends on the infection. Follow the instructions your doctor or pharmacist gives you, and ask them if you are unsure. Do not stop, shorten, or stretch a course on your own.
What you can do
You cannot stop bacteria from evolving. You can avoid giving resistant ones an easy advantage.
- Do not ask for antibiotics for a cold or flu. They will not help with a virus.
- Do not save or share antibiotics. Leftover pills may be the wrong drug, the wrong dose, or not needed at all.
- Take antibiotics exactly as prescribed. If you have questions, ask a doctor or pharmacist.
- Get recommended vaccines. Preventing an infection means no antibiotics are needed to treat it.
- Wash your hands and handle food safely. Fewer infections mean less pressure on the drugs we have.
Resistant bacteria can spread from person to person, so these habits protect other people as well as you.
Where to go next
To see the mechanism behind all this in more detail, read natural selection. For where new variation comes from, read mutation. For more examples measured directly by scientists, read observed evolution.