A few weeks ago I shared a post about how certain antibiotics vanquish the invading bacteria in your system by specifically targeting their support underwear, the bacterial cell wall. These antibiotics are excellent homing missiles, but they aren’t the only way to vanquish a bacterial infection. There other weapons in the antibiotic arsenal.
As I mentioned last time, the most important things for an antibiotic to do is recognise the difference between a human cell and a bacterial cell. This way, you don’t drop dead every time you take an antibiotic. Aside from the presence of a sturdy cell wall, another key difference for antibiotics is the mechanism that bacteria use to produce proteins. Proteins, we know, are awesome. They’re involved in every biochemical process going, without them you couldn’t possibly survive, you wouldn’t even exist. The same is true for bacteria, so if you can mess with the production of proteins, you can cause a whole heap of trouble. It’s like tampering with the supply lines of an army; once the production line is cut, it’s all going to fall apart pretty quickly.
So how are proteins made? They’re made by a construction team, headed up by a Building Foreman, the ribosome. The ribosome is an excellent protein architect; the Bob the Builder of the cell. Day in, day out, it sticks amino acids together in long complex chains, and sends them off into the cell to change the world. It has a team of support workers, of course and, importantly, it has a blueprint. Sticking amino acids together in any random order won’t produce very useful proteins, much like randomly sticking bricks together in piles doesn’t make a structurally sound building.
The instructions for building a protein are encoded in DNA; however the ribosome can’t read DNA. It’s not the brightest spark, and the only language it knows how to read is RNA. In order to synthesise proteins then, the cell first transcribes the passage of DNA that gives instructions for the right protein into RNA. This messenger RNA can then be read by the ribosome.
According to the instructions, the ribosome strings together amino acids in the correct order. The amino acids are ferried to the ribosome by transfer RNA molecules, these are the skivvies of the building site, running around, bringing amino acids to and fro, probably constantly getting shouted at for not bringing the right one at the right time, or not going fast enough. Without them, though, the whole construction team would fall apart. They briefly bind the ribosome, passing over the correct amino acid, so that it can be stuck to the previous one. The chain is then shoved along, and another amino acid is handed in.
If that’s the basic process of protein synthesis, what’s the difference between humans and bacteria? Not much, as it happens. The biggest difference is just that the ribosome is bigger in humans. The ribosome is a protein itself, and like any protein it is folded into a specific structure. That structure is also slightly different in the bacterial ribosome. Antibiotics, however, can take advantage of these seemingly minor differences, and they do so in a variety of ways.
Tetracycline is an undercover agent; it sneaks onto the building site and pretends to be a transfer RNA skivvy. However, once it reaches the ribosome and binds, it doesn’t hand over and amino acid. It just stops. The production stalls.
Chloramphenicol acts a little differently; it allows the transfer RNA to bind and hand over an amino acid, but once the new amino acid is in place, it stops it from being stuck to the previous one. The ribosome is holding two amino acids, but is prevented from sticking them together. The production stalls.
Erythromycin inhibits the stage where the chain is shoved along one step; it prevents the chain from moving so that the amino acids are jammed in the ribosome. This means that no further amino acids can be added. The production stalls.
Aminoglycosides, like gentamicin, don’t stall production. Instead they confuse the ribosome, cunningly persuading it that the message it reads in the RNA is wrong. Gentamicin tells the ribosome to add the wrong amino acids, in the wrong order, a truly sneaky bit of molecular manipulation that allows the ribosome to keep working, but producing faulty products that can’t work.
In all these cases, the process of protein production is compromised. The supply of functional, working proteins to the cell dries up, and the cell itself then cannot function. And BANG, you’ve won the war; the bacteria are once again vanquished. And no-one needed to wreck any support knickers at all, this time.