Antibiotics

Syllabus points

• Outline how penicillin acts on bacteria and why antibiotics do not affect viruses.
• Explain how bacteria become resistant to antibiotics, with reference to mutation and selection.
• Discuss the consequences of antibiotic resistance and the measures needed to reduce it.

What an antibiotic is

An antibiotic is a substance produced by a living organism, usually a fungus or a bacterium, that kills or inhibits the growth of bacteria.

• Bactericidal antibiotics kill bacteria. Penicillin is one.
• Bacteriostatic antibiotics stop them reproducing, leaving the immune system to clear the infection.

Antibiotics work by attacking structures or processes that bacteria have and human cells do not, which is what makes them safe to take. That principle explains both how penicillin works and why antibiotics are useless against viruses.

How penicillin works

Bacteria have a cell wall made of peptidoglycan, a mesh of polysaccharide chains cross-linked by short peptides. The wall is what stops the cell bursting, because bacterial cytoplasm has a much lower water potential than its surroundings and water is constantly entering by osmosis.

Penicillin inhibits the enzymes that form the cross-links in the peptidoglycan wall.

The consequence follows in steps:

1. A growing bacterium is continually making new wall.
2. With penicillin present, the new wall is made without cross-links, so it is weak.
3. Water continues to enter by osmosis, since the cytoplasm still has a lower water potential.
4. The weakened wall cannot resist the pressure, and the cell bursts, which is lysis.

Two things follow from this that are regularly examined.

Penicillin only affects bacteria that are actively growing. A dormant bacterium is not making new wall, so there is nothing for penicillin to disrupt. This is one reason tuberculosis is hard to treat.

Penicillin does not harm human cells, because human cells have no cell wall at all, so there is nothing for it to act on.

Why antibiotics do not work on viruses

A virus is not a cell. It has no cell wall, no ribosomes of its own, no cell surface membrane of the bacterial kind, and no metabolism.

Once inside a host cell, a virus uses the host's own enzymes and ribosomes to make copies of itself. There is no separate viral machinery for an antibiotic to target, and anything that did attack the machinery in use would damage the host cell too.

This is why prescribing antibiotics for a cold or influenza does nothing for the patient, and why doing so anyway is one of the main drivers of resistance.

How resistance arises

This is the part where the reasoning has to be exactly right, because a plausible-sounding wrong version is very common.

1. A bacterial population contains natural genetic variation, arising from random mutation. Mutations happen whether or not an antibiotic is present.
2. By chance, some mutations give resistance. A bacterium might produce an enzyme such as penicillinase that breaks the antibiotic down, or have an altered membrane protein that stops it entering, or an altered target site the antibiotic no longer fits.
3. When the antibiotic is used, it acts as a selection pressure. Non-resistant bacteria are killed.
4. The resistant bacteria survive and reproduce, passing the allele to their offspring. Bacteria reproduce very quickly, so this happens in days rather than generations of years.
5. Over time the frequency of the resistance allele in the population rises, and eventually the antibiotic is ineffective.

The mutation is not caused by the antibiotic. This is the point that separates a correct answer from an incorrect one. The antibiotic does not make bacteria become resistant; it selects the ones that already were. Saying that bacteria "become immune" or "adapt to" the antibiotic describes the wrong mechanism.

This is natural selection, complete and observable, which is why it is such a common exam context.

Horizontal transfer

Resistance also spreads sideways, not just by inheritance. Bacteria carry small circular DNA molecules called plasmids, and a plasmid carrying a resistance gene can be passed from one bacterium to another during conjugation, even between different species.

This is why resistance can appear in a species that has never itself been exposed to a particular antibiotic, and it is what makes multiple resistance in a single organism possible.

Why resistance matters

• Infections that were routine become difficult or impossible to treat, and people die of them.
• Surgery, transplants and chemotherapy all depend on being able to prevent or treat infection, so they become far more dangerous.
• MRSA, methicillin-resistant Staphylococcus aureus, spreads in hospitals where many vulnerable people are close together and antibiotic use is heavy.
• Multi-drug resistant tuberculosis requires far longer, more toxic and more expensive treatment, with a lower chance of cure.
• Developing a new antibiotic takes many years and a great deal of money, and resistance to it can emerge within a few years of release.

Reducing resistance

Each measure is aimed at reducing the selection pressure or at limiting spread.

• Prescribe antibiotics only when they are needed, and never for viral infections.
• Complete the course. Stopping early leaves the more resistant survivors alive and free to multiply. This is why DOTS exists for tuberculosis.
• Use narrow-spectrum antibiotics where the organism is known, so fewer species are exposed.
• Rotate the antibiotics used in a hospital, so no single one is under constant selection.
• Use a combination of antibiotics, since a bacterium resistant to one is usually still killed by the other, and the chance of a single organism being resistant to both is very small.
• Hospital hygiene: handwashing, isolating infected patients, and thorough cleaning, all of which limit spread rather than resistance itself.
• Restrict agricultural use. Antibiotics used routinely in livestock as growth promoters expose enormous bacterial populations to a constant low dose, which is close to ideal conditions for selecting resistance.

Common mistakes

• Saying the antibiotic causes the mutation. Mutation is random and prior; the antibiotic selects.
• Saying bacteria "become immune". Immunity is something a host has against a pathogen, not something a bacterium has against a drug.
• Saying penicillin dissolves or destroys the cell wall. It prevents new wall being cross-linked, so it only affects growing cells.
• Saying antibiotics do not affect viruses because viruses are too small. It is because they have no cellular machinery of their own to target.
• Explaining "finish the course" as making sure you feel better. It is about not leaving the most resistant survivors behind.