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Understand  –  Antibiotic resistance

Mutations and selection

Mutations can result in antibiotic resistance in bacteria. Resistant bacteria survive antibiotic treatment and can increase in numbers by natural selection.

Mutations

Bacteria grow and multiply fast and can reach large numbers. When bacteria multiply, one cell divides into two cells. Before the bacterium can divide, it needs to make two identical copies of the DNA in its chromosome; one for each cell. Every time the bacterium goes through this process there is a chance (or risk, depending on the end result) that errors occur; so-called mutations. These mutations are random and can be located anywhere in the DNA. Mutations can also form due to external factors like radiation or harmful chemicals.

Natural selection

While some mutations are harmful to the bacteria, others can provide an advantage given the right circumstances. Here, Darwin’s theory of natural selection comes in. If a mutation gives the bacterium an advantage in a particular environment, this bacterium will grow better than its neighbors and can increase in numbers – it is selected for.

Mutations can provide resistance to antibiotics

Mutations are one way for bacteria to become resistant to antibiotics. Some spontaneous mutations (or genes that have been acquired from other bacteria through horizontal gene transfer) may make the bacterium resistant to an antibiotic (See: Resistance mechanisms for information about how bacteria resist antibiotic action). If we were to treat the bacterial population with that specific antibiotic, only the resistant bacteria will be able to multiply; the antibiotic selects for them. These bacteria can now increase in numbers and the end result is a population consisting of mainly resistant bacteria.

The process of natural selection of resistant bacteria. Antibiotics kills sensitive bacteria but any resistant bacterium will survive. When the competition from other bacteria are gone, these resistant bacteria can increase in number.
Figure 1. Natural selection of antibiotic resistant bacteria. The starting point in this example is a large bacterial population mainly consisting of bacteria that are susceptible to antibiotics and a couple of bacteria that are antibiotic-resistant by chance. A bactericidal antibiotic is added, which kills most of the susceptible bacteria in the population, while the resistant bacteria survives. Only the resistant bacteria will continue to proliferate in the presence of the antibiotic and increases in number over time. The end result is a population of mainly resistant bacteria.

It is important to understand that selection of antibiotic resistant bacteria can occur anywhere an antibiotic is present at a selective concentration. When we treat an infection, selection can occur at any site in the body to which the antibiotic reaches. Thus, the antibiotic can select for resistance genes and mechanisms in both pathogenic bacteria and in commensal bacteria living in the body that have nothing to do with the infection in question. By using narrow-spectrum antibiotics (when possible), the risk of selecting for antibiotic resistance in the commensal flora decreases.

Video that explains natural selection of antibiotic resistance:

Selected Resources

Resource Description
Emergence and spread of antibiotic-resistant bacteria Narrated video-presentation from ReAct that describe how bacteria develop resistance and how bacteria can spread.
A cinematic approach to drug resistance Video that visualizes the development and spread of antibiotic resistant bacteria in real time, using a giant petri dish with different concentrations of antibiotics. With explanatory article.
The rise in antibiotic resistance Animation of selection of resistant bacteria in the body, some resistance mechanisms and how they may spread.
What causes antibiotic resistance? This TED-Ed video gives an overview of how antibiotics function, how bacteria evolve to resist their action and how selection of resistant bacteria works (5 min). Also available in Spanish.
Natural Selection and the Rock Pocket Mouse Movie from HHMI BioInteractive about a real-life example of natural selection (11 min).
Mutations – selection: the bacteria resist Movie about natural selection of antibiotic resistant bacteria (5 min). Also in text above.