Prokaryotic vs Eukaryotic Cells

Almost every microbe that causes disease is a single cell. That cell is built one of two ways. It is either a prokaryote, a small cell with its DNA loose in the cytoplasm, or a eukaryote, a larger cell that locks its DNA inside a nucleus. Bacteria are prokaryotes. Fungi and protozoa are eukaryotes. Human cells are eukaryotes too. That one split in building plans is not just trivia. It is the reason a drug can flood the bloodstream, wreck the bacteria, and leave the person unharmed. This chapter takes a bacterial cell apart piece by piece. It starts at the wall that gives the cell its shape. It ends at the spore that can sit on a bed rail for ten years.

Section 1Two kinds of cell

The deepest split in biology

You could sort living cells in many ways. One line runs deeper than all the rest. Does the cell keep its DNA inside a membrane-bound nucleus, or not? Cells that do not are prokaryotes. The word comes from Greek roots that mean "before the nut." The nut is the nucleus. Cells that do are eukaryotes, which means "true nut." This is not a small matter of style. It comes with a whole package of other traits. Once you know which side of the line a microbe sits on, you know how it is built, how fast it grows, and which drugs can touch it.

Prokaryotes are the bacteria and the archaea. They are small. Most run 0.2 to 2 µm across. They are plain inside, with one circular chromosome floating loose in the cytoplasm. Archaea are prokaryotes too, though their walls are made of other material, not peptidoglycan. Few of them make people sick. Eukaryotes cover the fungi, protozoa, plants, animals, and every human cell. They are usually ten to a hundred times wider. Inside, they are far more involved. So when you call an infection "bacterial" rather than "fungal," you are really naming which kind of cell is being fought.

What prokaryotes lack, and what they have

The headline is what prokaryotes are missing. They have no nucleus. They have no other membrane-bound organelles either. No mitochondria. No endoplasmic reticulum. No Golgi apparatus. All of that chemistry happens out in the open cytoplasm, or against the inner face of the plasma membrane. But plain does not mean helpless. Prokaryotes make up for the missing rooms with tough gear on the outside. Most wear a stiff cell wall. Many add a slimy capsule. Many carry flagella to swim and pili to stick. The rest of this chapter is about those parts.

One more difference is easy to miss. It is also huge for medicine. Both kinds of cell build proteins on a ribosome. The two machines are not the same size. Prokaryotes use a 70S ribosome. Eukaryotes use a larger 80S ribosome. That size gap is a gift. A drug can be shaped to jam the 70S machine and ignore the 80S one.

Why the split is a drug target

Here is the payoff. Bacterial cells carry parts that human cells simply do not have. A peptidoglycan wall. A 70S ribosome. Enzymes of their own. A drug can go after one of those parts. The bacterium dies and the eukaryotic cells around it are left alone. This idea is called selective toxicity, and it is the whole reason antibacterial treatment is possible. Penicillin blocks cell-wall building, and human cells never build a wall. Many antibiotics grab the 70S ribosome, which human cells do not own. The wider the gap between microbe and host, the safer the drug.

Section 2Inside the bacterial cell

The plasma membrane is the real boundary

Several layers wrap a bacterium. The plasma membrane, the cell wall, and, in Gram-negatives, an outer membrane. Together they are the cell envelope. Everything the envelope holds is cell contents: cytoplasm, ribosomes, nucleoid, and plasmids. Work from the outside in. The wall gives a bacterium its shape. But the plasma membrane is the layer that actually keeps the cell alive. It is a phospholipid bilayer, which means two sheets of fatty molecules. Their water-loving heads face out and their water-fearing tails tuck away inside. Proteins are peppered all through it. The membrane is selectively permeable, so it decides what crosses. Nutrients in. Wastes out. Ions held in balance. Prokaryotes have no mitochondria, so the membrane takes on one more job. It runs the electron transport chain and makes the cell's energy right there in the membrane.

That makes the membrane a tempting drug target. It is also a risky one. Bacterial and human membranes are built from similar chemistry. Drugs that punch holes in a membrane tend to harm the host as well. The polymyxins, such as colistin, do exactly that. They are held in reserve as last-resort agents against highly resistant Gram-negative bacteria, because they can also injure the kidneys.

Cytoplasm, ribosomes, and inclusions

Fill the membrane and you have the cytoplasm. It is a crowded, water-based gel, and nearly all of the cell's chemistry happens in it. Tens of thousands of 70S ribosomes hang in that gel. These are the protein factories from Section 1, and whole families of antibiotics aim at them. Aminoglycosides. Tetracyclines. Macrolides. Many bacteria also stock spare food in inclusions. These are small granules of stored carbon, phosphate, or sulfur. The cell draws on them when food runs short.

The nucleoid and plasmids

A prokaryote has not lost its DNA. The DNA is simply not gift-wrapped in a nucleus. The single circular chromosome coils into a dense zone called the nucleoid. No membrane surrounds it, so the DNA touches the cytoplasm directly. This is one reason bacteria can grow so fast. Transcription and translation happen in the same space at the same time.

Many bacteria also carry extra loops of DNA called plasmids. They are far smaller than the chromosome and sit apart from it. A cell can usually live without them. But plasmids often carry the genes that matter most in an outbreak. Antibiotic-resistance genes. Toxin genes. The tools to pass those genes to other bacteria. A plasmid can hop from one bacterium to another. That is how resistance can race through a unit faster than any single organism could breed.

Section 3The cell wall

Peptidoglycan, the mesh that holds the shape

Outside the membrane, most bacteria wear a stiff cell wall made of peptidoglycan, also called murein. The human body holds none of it anywhere. Picture a chain-link fence wrapped all the way around the cell. Long sugar chains run side by side. Short chains of amino acids tie them to one another. That cross-linking turns a floppy bag into a rigid mesh. The mesh is strong enough to resist the cell's own osmotic pressure, which would otherwise pull in water until the cell swelled and burst. The wall is also what sets a bacterium's shape: rod, sphere, or spiral. Because nothing like it exists in a human cell, the wall is a clean drug target.

This is exactly where the beta-lactam antibiotics work. Penicillins, cephalosporins, and carbapenems block the enzymes that stitch the peptidoglycan cross-links. The bacterium keeps trying to grow. The wall can no longer hold. The cell ruptures. Human cells have no wall to protect, so these drugs are among the safest antibiotics we have.

Gram-positive and Gram-negative walls

Not all walls are built the same way. That difference is the most useful early clue a microbiology lab can hand over. The Gram stain sorts bacteria into two great camps. It works by how the wall holds a purple dye.

Gram-positive bacteria have a thick peptidoglycan layer on the outside. It traps the crystal violet dye, so the cell stays purple. Examples: Staphylococcus, Streptococcus, Enterococcus, Clostridioides.

Gram-negative bacteria have only a thin peptidoglycan layer. On top of it they add a second outer membrane. Alcohol strips that outer membrane away, so the purple dye washes out of the thin wall. The cell then takes up the pink counterstain and looks red or pink. Examples: Escherichia coli, Klebsiella, Pseudomonas, Neisseria.

A few organisms fit neither camp. Mycobacterium has a waxy wall that needs an acid-fast stain instead. Mycoplasma has no cell wall at all, so beta-lactams cannot touch it.

Why the Gram stain still runs the show

The Gram result is more than a color. It predicts behavior. That extra outer membrane makes Gram-negative bacteria harder to kill, because it blocks many drugs from ever reaching the wall. The outer membrane also carries a molecule with enormous clinical weight: lipopolysaccharide (LPS), better known as endotoxin. Gram-negative cells die and break apart. LPS spills into the blood. The immune system answers violently. Fever. Blood pressure that drops away. At the far end, septic shock. This is why a Gram-negative bloodstream infection can spiral so fast.

Section 4External structures

The capsule is a slippery shield

Some bacteria wrap themselves in a thick, sticky outer layer called a capsule. A looser, messier version is called a slime layer. A cell does not need a capsule to stay alive. Where one exists, though, it counts for a great deal. A capsule is a major virulence factor. It is so slippery that immune cells struggle to grab and swallow the bacterium, a trick called resisting phagocytosis. That is why the most dangerous strains of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis are the ones with capsules. There is good news in it too. The capsule is what several key vaccines are aimed at. Teach the immune system to spot the capsule, and it can clear the organism before meningitis or pneumonia ever starts.

Flagella: swimming and chemotaxis

Flagella are long, whip-like tails. They rotate like a propeller and push a bacterium through liquid. Bacteria do not wander at random. They steer toward nutrients and away from toxins, a directed movement called chemotaxis. Motility can be a virulence trait in its own right. It helps organisms like E. coli and Pseudomonas climb a urinary catheter or reach fresh tissue to settle in. The number and the position of the flagella is also a useful clue to a bacterium's identity. One tail at one end. A tuft at one end. Tails all over the cell.

Pili and fimbriae: sticking and swapping genes

Two shorter appendages finish off the outside of the cell. The naming is easy to mix up, so hold the two apart.

Fimbriae are short, hair-like fibers, and there are many of them. A bacterium uses them to attach to surfaces and to host cells. Attachment is the first step of nearly every infection. A microbe that cannot stick simply gets flushed away. Fimbriae are exactly how E. coli grips the lining of the bladder to start a urinary tract infection. They also anchor bacteria into the slimy communities called biofilms on catheters and implants.

Pili are usually longer and far fewer, often just one or two per cell. The sex pilus, also called the conjugation pilus, has a different job. It builds a bridge to another bacterium and pulls it close. The two cells then swap DNA in a process called conjugation. This is one of the main ways antibiotic-resistance plasmids move from cell to cell.

Section 5Endospores

What an endospore is

A handful of Gram-positive bacteria can do something no other microbe can. The main groups are the genera Bacillus and Clostridioides/Clostridium. When conditions turn hostile, they seal a copy of their DNA inside an armored survival capsule called an endospore. The spore is not a way to reproduce. One cell makes exactly one spore. It is a way to wait out disaster. Inside its tough coat, the spore is dormant. No growth. No chemistry. Nothing soft to attack. It can persist for years, even decades, in soil, on surfaces, or on hospital equipment.

How a spore forms and wakes up

The normal, actively growing bacterium is called the vegetative cell. When it senses starvation or other stress, it begins sporulation. First it copies its chromosome. Then it walls off a small patch of cytoplasm around that DNA. Then it wraps the patch in layer after protective layer. A dense core stripped of most of its water. A thick cortex. A tough protein coat. The rest of the original cell then breaks down and releases the finished endospore.

The spore stays dormant until conditions improve. When nutrients return, it germinates. The coat cracks. Water rushes back in. Metabolism restarts. It grows back into an ordinary, dividing vegetative cell. This next part matters most. The vegetative cell is the form that causes active disease, and the form that ordinary antibiotics and disinfectants can kill. The spore is the form that survives to start the cycle over again.

Why spores defeat routine disinfection

A spore holds very little water, and its armor comes in layers. Those two facts together make it extraordinarily hard to kill. It shrugs off heat, drying, radiation, and most chemical disinfectants. That includes the alcohol-based hand rubs that work so well against almost everything else. This is not an academic point. It changes how hands are washed and how rooms are cleaned. Two organisms show why.

Clostridioides difficile spreads by spores that survive on bed rails, commodes, and hands. Alcohol gel does not kill them. So for a case of C. diff the rule is soap-and-water handwashing, which physically washes spores away, plus a sporicidal cleaner such as diluted bleach for surfaces. Clostridium tetani and Clostridium botulinum spores lurk in soil and in improperly canned food. And because spores can shrug off boiling, true sterilization of instruments requires an autoclave, which is pressurized steam at 121°C, not just hot water.

One picture pulls the whole chapter together. Every drug named in these five sections strikes a part of the cell you just took apart. Some never get that far. The model below maps each target, and shows what stops a drug on the way in.

ReferenceWords worth knowing

A quick reference for the terms in this chapter. Skim it now, or circle back whenever a word trips you up.

Capsule

A thick, sticky outer layer around some bacteria that resists phagocytosis; a virulence factor and vaccine target.

Cell envelope

The layers enclosing a bacterium — the plasma membrane, the cell wall, and any outer membrane.

Cell wall

The rigid peptidoglycan layer outside the membrane that gives a bacterium its shape and keeps it from bursting.

Chemotaxis

Directed movement by flagella toward nutrients or away from harmful chemicals.

Conjugation

Transfer of DNA, often a plasmid, between bacteria through a sex pilus.

Endospore

A dormant, highly resistant survival form made by some Gram-positive bacteria; not a means of reproduction.

Endotoxin (LPS)

Lipopolysaccharide in the Gram-negative outer membrane that triggers fever, low blood pressure, and septic shock when released.

Eukaryote

A cell whose DNA is enclosed in a membrane-bound nucleus and that holds organelles; fungi, protozoa, and human cells.

Fimbriae

Numerous short hair-like appendages used to attach to surfaces and host cells; they enable biofilms and adhesion.

Flagella

Long whip-like appendages that rotate to drive a bacterium through liquid.

Gram-negative

Bacteria with a thin peptidoglycan wall plus an outer membrane; they stain pink and carry endotoxin.

Gram-positive

Bacteria with a thick peptidoglycan wall and no outer membrane; they retain crystal violet and stain purple.

Nucleoid

The membrane-free region of a prokaryote where the circular chromosome is coiled.

Peptidoglycan

The mesh of cross-linked sugars and amino acids that makes up the bacterial cell wall; the target of beta-lactam antibiotics.

Pili (sex pilus)

Long, few appendages that bridge two bacteria to transfer DNA by conjugation.

Plasma membrane

The selectively permeable phospholipid bilayer that controls transport and generates energy in prokaryotes.

Plasmid

A small circular loop of DNA separate from the chromosome that often carries resistance or toxin genes.

Prokaryote

A cell with no membrane-bound nucleus and no organelles; bacteria and archaea.

Ribosome (70S / 80S)

The protein-building machine; prokaryotes use the smaller 70S, eukaryotes the larger 80S — a key antibiotic target.

Selective toxicity

Harming a microbe while sparing the host by targeting a structure the microbe has and the host lacks.

Sporulation

The process by which a stressed vegetative cell forms an endospore; reversed by germination.

Vegetative cell

The active, growing, dividing form of a bacterium — the form that causes disease and is killed by drugs and disinfectants.