I’m fairly sure that most of you will have taken antibiotics at some point or another in your lives, whether for a chest infection, for toothache, for an ear or sinus infection, or for something completely different, we’re all used to the idea that we can take tablets and squish a bacterial infection out of existence. But have you ever wondered how that works, exactly?
I think it’s kind of amazing that we can do this, selectively blast invaders out of our systems, because the thing about antibiotics is that, unlike a lot of drugs, you’re not targeting anything human. Instead, you’re trying to vanquish an invading force. If your immune system is an army, fighting to repel pathogenic invaders, then antibiotics are a back-up force, heavily armed with missiles. Naturally, if you’re drafting in an elite fighting force you want your missiles to be precise. It would be really helpful if your antibiotic missile could tell the difference between the bacterial invaders that it’s designed to blow to smithereens, and any civilian human cells hanging around the place. After all, there’s no use in killing all the infecting bacteria, feeling better and then dropping dead because the drugs got a bit carried away and also killed the cells of your body. Happily, there are some key differences between bacterial cells and human cells, and it is these differences that antibiotics take advantage of.
The first big difference between bacterial cells and animal cells is that bacterial cells have a cell wall. The role of the bacterial cell wall is to give the cell structure and shape, a bit like a giant pair of control pants, and to support the high osmotic pressure inside the cells, so they don’t burst. By contrast, animal cells are happily wobbling along, surrounded by a membrane but with no need for advanced corsetry. This means that if antibiotics can target the bacterial cell wall, they’ll be nice and specific, like homing missiles set to locate giant bacterial pants. The beta-lactam class of antibiotics, which includes penicillin, amoxicillin and ampicillin, amongst others, do just this.
The bacterial cell wall is formed from peptidoglycan, an interlocking mesh of sugars and amino acids. This mesh is built up in a number of stages, and one of the final steps is to build molecular bridges between the sugary-amino acid backbone strands, cross-linking them together. This step is catalysed by a group of enzymes known as transpeptidases or penicillin-binding proteins (PBPs). When PBPs are working normally, they attach the amino acids to the sugars, and build up the mesh network that will form the control pants and give the cell structure, and a fantastic smooth silhouette.
Beta-lactam antibiotics inhibit PBPs; they sneak into the active site of the PBP, where the amino acid would usually snuggle in ready to get attached, and once there they make chemical changes to the PBP that stop it from working. By doing this, they can prevent the cross-linking of the peptidoglycan layer, which effectively blocks the synthesis of the cell wall. Without the ability to synthesise more cell well, bacteria cannot grow and they cannot divide. Well, they can certainly try, but they won’t have proper support from their underwear and therefore their osmotic pressure will cause them to blow up. Much like if I ate too much cake and my control pants had a rip in a crucial place. That’s how beta-lactam antibiotics work; they are homing missiles that blow bacterial cells up by targeting their control pants. Obviously.
Now, beta-lactam antibiotics are not the only class of antibiotics to target the bacterial cell wall. Another class, glycopeptides, also work in a similar way. Glycopeptides include antibiotics like vancomycin and teicoplanin, and they are even more specific than beta-lactams. Instead of targeting bacterial cells, they specifically target a certain type of bacteria. Bacteria can be classed as either Gram-positive or Gram-negative. Gram-positive bacteria have a far higher internal pressure than Gram-negative bacteria (~20 atmospheres compared to around 5 atmospheres in Gram-negative cells), this means that their control pants need serious reinforcement to prevent them bursting out. As a result, the bacterial cell wall in Gram-positive bacteria is considerably thicker, and formed from a lot more peptidoglycan. It is also assembled slightly differently; the backbone chains are assembled using a slightly different mechanism. This is the difference that vancomycin homes in on; it is effective only against Gram-positive bacteria. Rather than inhibiting an enzyme, like the beta-lactams, it binds to the building blocks of the backbone itself and renders them unable to join with other building blocks. In this case there isn’t simply a rip in the control knickers, this time the thread that they’re made from is faulty.
So that’s how two classes of antibiotics work, by targeting the bacterial cell wall. However, these aren’t the only two classes of antibiotics. There are a wide range of antibiotics out there, and they use a range of different mechanisms to kill or inhibit the growth of your invading bacteria. That is precisely why this post is labelled Part I, the antibiotics will be back, and next time stopping the bacteria might not be as simple as ripping their knickers off.