Chapter 3

Prokaryote vs eukaryote

Prokaryote means “before the nucleus”. Every other difference follows from that one, and one of them — the ribosome — is the reason antibiotics can work at all.

Both cells at one scale

The bacterium is the small rod at the left. The circle beside it is the enlargement — that is the honest size difference.

Fig. 1A prokaryotic and a eukaryotic cell drawn to the same scale, with the bacterium enlarged alongside.

The ten differences

Read the third column when there is one — it is the part an essay question is actually asking about.

Feature	Prokaryotic	Eukaryotic	Why it matters
Nucleus	None — DNA sits in the cytoplasm in a region called the nucleoid	A true nucleus, bounded by a membrane	This is the difference the word "prokaryote" names: before the nucleus.
Chromosome	One circular chromosome, often with plasmids	Several linear chromosomes, wound on histones	—
Membrane-bound organelles	None	Mitochondria, ER, Golgi, lysosomes and more	With no mitochondria, a bacterium makes its ATP at the cytoplasmic membrane.
Ribosomes	70S — a 50S and a 30S subunit	80S — a 60S and a 40S subunit	The basis of selective toxicity: a drug can bind 70S and leave our 80S alone.
Cell wall	Peptidoglycan in bacteria; other polymers in archaea	Cellulose in plants, chitin in fungi, none in animals	Another drug target, because human cells have no wall to attack.
Size	About 1 µm	10 to 100 µm	A eukaryotic cell can be a thousand times the volume of a bacterium.
Division	Binary fission	Mitosis or meiosis	—
Cytoskeleton	Simple	Complex — microtubules, actin, intermediate filaments	—
Flagellum	Filament, hook, basal body; rotates	A 9+2 arrangement of microtubules; whips	Same word, entirely different structure and motion.
Examples	Bacteria, archaea	Fungi, protozoa, algae, plants, animals	—

Selective toxicity

A useful antimicrobial has to kill the microbe without killing the patient. That is only possible where the two cells differ, so every difference in the table above is a possible drug target — and the good targets are the ones with no human counterpart at all.

The cell wall is the cleanest example: human cells have none, so a drug that stops peptidoglycan cross-linking has nothing of ours to damage. The ribosome is the subtler one. Ours are 80S and a bacterium’s are 70S, so a drug shaped to the 70S subunits stops bacterial protein synthesis and leaves ours running.

Wall-active drugs

Penicillins and cephalosporins block peptidoglycan cross-linking. No human cell has a wall, so the margin of safety is wide.

Ribosome-active drugs

Tetracyclines and aminoglycosides bind the 30S subunit; macrolides bind the 50S. Both are parts an 80S ribosome does not have.

Why antifungals are harder

Fungi are eukaryotes. Far less of their cell is unlike ours, so there is much less to aim at — which is why antifungal drugs tend to be more toxic than antibacterials.