A2 Biology 9700: Antibiotic Resistance as Natural Selection

A species of bacterium infecting hospital patients is treated with a newly introduced antibiotic. Before this antibiotic was ever used on patients, a very small number of bacteria in the population already carried a rare mutant allele that altered a bacterial cell-surface protein, so that the antibiotic could no longer bind to it effectively.

(a) Explain why it is incorrect to say that exposure to the antibiotic caused this mutant allele to appear in the bacterial population. [2]

(b) Explain, in terms of natural selection, how the proportion of the bacterial population carrying the resistance allele increases once the antibiotic is introduced and used repeatedly. [4]

(c) A patient stops taking their course of this antibiotic as soon as their symptoms disappear, rather than completing the full course prescribed. Suggest why this practice increases the risk that a fully antibiotic-resistant bacterial population will develop in that patient. [2]

Part (a): Mutation is random, not caused by the antibiotic

A common misconception is that the antibiotic “made” the bacteria resistant. In reality, mutations occur randomly and spontaneously (for example, as copying errors during DNA replication) and can happen at any time, independent of whether the antibiotic is present. In this scenario, the resistance allele already existed, in a very small number of bacteria, before the antibiotic was ever introduced.

The antibiotic itself does not cause or direct this mutation. Its role only begins afterwards: it acts as a selection pressure on variation (the mutant allele) that already existed in the population purely by chance.

Part (b): How resistance spreads by natural selection

Once the antibiotic is introduced:

Bacteria without the resistance allele are killed, or prevented from reproducing, by the antibiotic.
The rare bacteria that do carry the resistance allele are not affected in the same way, so they survive and continue to reproduce. This is differential survival and reproduction based on genotype, exactly the mechanism of natural selection.
Bacteria reproduce asexually, by binary fission, so every surviving resistant bacterium produces offspring that are genetically identical to itself, each carrying a copy of the resistance allele.
Because bacterial generation times are very short, this process repeats rapidly: with each generation, a larger proportion of the population descends from resistant survivors, so the frequency of the resistance allele increases while non-resistant bacteria become proportionally rarer.
Over enough generations, the population becomes predominantly (or entirely) resistant. This is a clear example of directional selection. The antibiotic shifts the population’s phenotype composition towards resistance.

Part (c): Why stopping a course early is risky

Completing a full course of antibiotics is intended to expose the bacterial population to the drug for long enough to kill essentially all of the bacteria, including those that are only partially or moderately resistant.

If a patient stops early:

Only the most susceptible bacteria (least resistant) are likely to have been killed so far.
The bacteria that remain are, on average, more resistant than the original population, but the antibiotic exposure ends before they too can be eliminated.
These comparatively resistant survivors can then multiply largely unopposed, increasing the proportion of resistant bacteria in the patient’s body more than a completed course would have allowed.

This is why incomplete antibiotic courses are considered a significant contributor to the spread of antibiotic resistance.

Final answers

(a) The mutation arose randomly, before and independently of antibiotic exposure; the antibiotic selects for a pre-existing allele rather than causing it.
(b) Non-resistant bacteria are killed; resistant bacteria survive, reproduce asexually and pass on the resistance allele to all offspring; over generations the resistance allele’s frequency increases, directional selection.
(c) Stopping early kills only the most susceptible bacteria, leaving comparatively resistant survivors free to multiply, increasing the risk of a fully resistant population developing.