Adaptation in Real Time: Antibiotic and Pesticide Resistance

A miracle drug meets evolution

In 1928, Alexander Fleming noticed that a mould growing on one of his bacteria dishes had killed the bacteria around it. The mould made penicillin, the first widely used antibiotic. By the 1940s, penicillin was saving countless lives from infections that used to be deadly.

Within a few years of its wide use, doctors were already finding bacteria that penicillin could not kill. Today, some infections resist almost every antibiotic we have. Health agencies around the world, including the Public Health Agency of Canada, call antimicrobial resistance a serious threat to public health.

How does a population of bacteria "learn" to beat a drug? It doesn't learn. It evolves, by natural selection, fast enough that we can watch it happen.

How resistance evolves

The process follows the same steps you learned for natural selection.

1. Variation already exists. In a large population of bacteria, random mutations mean that a few cells may already carry an allele that lets them survive the antibiotic (for example, a gene for an enzyme that breaks the drug down, or a pump that pushes it out). The antibiotic did not cause these mutations.
2. The antibiotic is the selective agent. It kills the sensitive cells.
3. Resistant cells survive and reproduce. Bacteria can divide every 20 to 30 minutes in good conditions, so survivors quickly rebuild the population.
4. The population changes. The new population is mostly resistant. The next time the same antibiotic is used, it may not work.

This is what C3.2 means by individual organisms adapting to their environment: an individual bacterium does not change. Some individuals already had a slight genetic variation that let them survive, and the population became adapted.

Bacteria share their resistance

Bacteria have a trick that makes resistance spread even faster. Many resistance genes are carried on plasmids, small rings of DNA separate from the main chromosome. During conjugation, one bacterium can pass a copy of a plasmid to another, even to a different species of bacteria. This is horizontal gene transfer: genes passing sideways, not just from parent to offspring.

So once resistance has evolved in one type of bacteria, it can jump to others, including ones that cause disease.

Why misuse makes things worse

Every use of an antibiotic selects for resistance, so we want to use them only when they are needed.

• Antibiotics do not work on viruses. Colds and the flu are caused by viruses. Taking antibiotics for them gives no benefit and still selects for resistant bacteria that live in your body.
• Take antibiotics exactly as prescribed by a doctor, nurse practitioner or pharmacist, and never use leftover pills or someone else's prescription.
• Prevent infections in the first place: hand washing, vaccines and safe food handling mean fewer antibiotics are needed.
• Agriculture: antibiotics have been used in farm animals, sometimes to make them grow faster rather than to treat illness. This selects for resistant bacteria that can reach people. Since December 2018, Canada has required a veterinary prescription for medically important antibiotics given to animals, including farm animals.
• Hospitals are hot spots, because many patients receive antibiotics. Bacteria such as MRSA spread there; careful hand hygiene and infection control slow them down.

Same story, different organisms: pesticides and herbicides

Any strong selective agent can cause resistance to evolve.

• Insects: the Colorado potato beetle, a major pest of potato crops in Canada, has evolved resistance to many different insecticides. Mosquitoes in many countries evolved resistance to DDT.
• Weeds: some populations of Canada fleabane in Ontario have evolved resistance to glyphosate, a widely used weed killer. Farmers then need other methods to control them.
• Fungi and viruses can also evolve resistance to fungicides and antiviral drugs.

Strategies to slow resistance include rotating different pesticides, using lower overall amounts, combining chemical control with crop rotation and natural predators (integrated pest management), and leaving some untreated refuge areas so susceptible insects remain to breed with resistant ones.

Watching evolution in a lab

Since 1988, the American biologist Richard Lenski and his team have grown 12 populations of the bacterium E. coli in the same simple conditions, freezing samples along the way so they can compare ancestors with descendants. The populations have now passed more than 75 000 generations. They have evolved to grow faster in their environment, and one population evolved the new ability to use a nutrient (citrate) that E. coli normally cannot use when oxygen is present. It is one of the clearest direct observations of evolution.