Resistance evolves when a chemical kills susceptible individuals but allows rare variants to survive and reproduce. Over generations, these survivors become common, reducing drug or chemical effectiveness in medicine, agriculture, and public health.

What “resistance” means in an evolutionary context

Resistance is an inherited ability of an organism or cell to survive and reproduce despite exposure to a drug (e.g., antibiotics, chemotherapy) or chemical (e.g., pesticides, herbicides). It is a population-level evolutionary change, not an individual “getting used to” a chemical.

Chemicals create strong selective pressures because they often cause large differences in survival and reproduction between phenotypes.

Core mechanism: selection on heritable variation

Key requirements for resistance evolution

• Variation exists: within a population, some individuals are more tolerant than others.

• Variation is heritable: differences are caused by genetic changes that can be passed on.

• Differential reproductive success: resistant individuals contribute disproportionately to the next generation after exposure.

Why resistance evolves rapidly in many systems

• Large population sizes increase the chance that resistant variants already exist.

• Short generation times (especially microbes and pests) allow fast shifts in allele frequencies.

• High-intensity selection (high mortality in susceptible types) produces strong, often directional selection toward resistance.

Resistance to antibiotics (bacteria)

How resistant bacteria arise

Resistance can be present before treatment begins or appear during population growth:

• Spontaneous mutations can alter:

  • Drug targets (e.g., modified ribosomal proteins)

  • Membrane permeability (reduced drug entry)

  • Efflux pumps (increased drug export)

  • Enzymatic inactivation (drug-destroying enzymes)

• Horizontal gene transfer (HGT) can spread resistance genes between bacteria:

  • Conjugation via plasmids carrying resistance genes

This diagram shows bacterial conjugation, where a donor cell forms a pilus to connect to a recipient cell and transfers a plasmid DNA strand. Conjugation is evolutionarily important because plasmids can carry antibiotic-resistance genes and spread them rapidly through a bacterial population, even across different strains or species. Source

• Transformation by uptake of free DNA

• Transduction via bacteriophages

How antibiotic use creates strong selection

When antibiotics are present:

• Susceptible bacteria die or fail to reproduce.

• Resistant bacteria survive, reproduce, and can rapidly dominate the population.

• After treatment, resistant bacteria may persist and spread to new hosts, especially in settings with high antibiotic exposure.

This infographic summarizes how antibiotic-resistant bacteria move among humans, animals, food, and environmental reservoirs, emphasizing transmission pathways rather than just within-host selection. It helps connect the evolutionary origin of resistance (selection) to the public-health outcome: resistant strains spreading through interconnected systems. Source

Practices that intensify selection for resistance

• Unnecessary antibiotic use (e.g., viral infections)

• Incorrect dosing (too low to eliminate partially resistant cells)

• Incomplete courses that leave survivors to repopulate

• Widespread use in agriculture that exposes many bacterial populations repeatedly

Resistance to antivirals (viruses)

Viruses can evolve resistance when antiviral drugs block replication but variants with altered viral proteins replicate despite treatment. Rapid evolution is promoted by:

• High replication rates

• High mutation rates in many viral genomes

• Large within-host populations that provide many opportunities for resistant variants to be selected

Resistance to chemotherapy (cancer cells)

Chemotherapy resistance is an evolutionary process occurring within the body:

• Tumors often contain genetic heterogeneity, meaning different cancer cell lineages carry different mutations.

This figure illustrates clonal evolution in tumors: sequential mutations generate multiple subclones, producing genetic heterogeneity within the same cancer. Therapy can then act as a selective filter, preferentially reducing sensitive lineages while allowing pre-existing resistant subclones to expand and drive relapse. Source

• Chemotherapy acts as a selective agent:

  • Sensitive cancer cells die.

  • Resistant clones survive and expand, leading to relapse or reduced treatment efficacy.

Common resistance mechanisms include:

• Altered drug targets

• Increased DNA repair

• Drug efflux (transporters removing drugs from cells)

• Failure to undergo apoptosis despite damage

Resistance to herbicides (weeds) and pesticides (insects)

Herbicide resistance

Herbicides impose selection in plant populations exposed repeatedly to the same mode of action. Resistance may evolve through:

• Target-site changes that reduce herbicide binding

• Metabolic resistance that detoxifies the herbicide

• Changes in uptake, transport, or sequestration of the chemical

Pesticide (insecticide) resistance

Insect populations can evolve resistance via:

• Target-site mutations in nervous system proteins

• Increased detoxification enzymes

• Behavioral avoidance (reduced contact with treated surfaces)

Because many pests have large population sizes and multiple generations per season, allele frequencies can shift quickly when selection is strong and consistent.

What slows (but rarely stops) resistance evolution

Reducing the strength and consistency of selection can delay resistance:

• Combination therapy (multiple drugs with different targets) reduces the probability that a single genotype is resistant to all agents.

• High adherence and appropriate dosing reduce survival of partially resistant variants.

• In agriculture, strategies such as maintaining refuges (areas without pesticide/herbicide exposure) can preserve susceptible individuals, reducing the relative advantage of resistant genotypes.

• Targeted, limited application decreases the number of selection events and the size of exposed populations.