How Drugs Work: Antibiotics Part III

So far in the series on how antibiotics kick bacterial butt, we’ve seen support knickers blown up and the molecular Bob the Builder get blocked. And we’re still not done. There are yet more ways to destroy invading bacteria, there are more weapons in the pharmaceutical arsenal.

Last time, I mentioned how crucial proteins are to life; how they’re involved in every biochemical process going, and how without them you couldn’t possibly survive, you wouldn’t even exist. So, yes, you need proteins. And some antibiotics work by blocking the production of new proteins.

Other antibiotics, however, go beyond that. The instructions that tell the bacteria how to build all the proteins necessary for them to go on living are blueprinted in DNA. So the fluoroquinolone antibiotics don’t faff around blocking protein synthesis; instead they go right back to the point of origin; they tamper with the DNA.

Bacterial DNA is helical, like our DNA, but rather than existing all squished up and compressed into chromosomes, bacterial DNA is circular. The majority of the time this is fine, bacterial cells carry around a happy little circle of twisted helical DNA. However, there is a potential problem; in order for the DNA to be replicated, or for it to be read and translated into protein, it must untwist. The relevant section needs to unfurl itself, and unzip itself, so that the information it contains can be read. The problem is that if you untwist one section of the DNA, the rest of the DNA has to take on some extra twists, in order to take the strain. This creates tension. It’s exactly like twisting two elastic bands together; the tighter the twists, the more tension the bands hold.

This is where a protein called DNA gyrase comes in. DNA gyrase cuts and bends DNA to form supercoils, thus relieving the tension and allowing the DNA to be read. It’s basically a molecular massage therapist, unkinking knots and relaxing the tension in the DNA. Unless, of course, there are fluoroquinolones in the area; these medicinal soldiers disable DNA gyrase. The tension in the DNA cannot be relieved, and the whole process of untwisting and reading the DNA falls apart.

Just goes to show how important it is to stay relaxed, hey?

Fluoroquinolones kill bacteria in two ways; first you have to remember that bacteria replicate inside the body. One bacterium alone cannot storm the castle, although it might give it a shot I suppose, if it was feeling heroic, it would pretty much be doomed to failure. Your immune system can cope with one bacterial cell.

So, instead of doomed solo missions behind enemy lines, bacteria sneak in alone, and then multiply once they’re in. And each time they multiply, they need to replicate their DNA, in order to pass on the blueprints for making bad-ass proteins to all the new bacteria. Unless of course, some sneaky soldier has tied up all the DNA gyrase massage therapists. In that case, new DNA cannot be synthesised, and now new bacteria can be produced. The immune system can slowly close in on the bacteria that remain.

That isn’t all the fluoroquinolones do, however. Replicating DNA is not the only reason for it to untwist; it also needs to do so when it is being transcribed, ready to be translated into protein. If you can’t read the DNA blueprint, you can’t make new protein. Basically, you’re screwed.

So that’s it, the final way in which antibiotics can work to take back your body from the invading bacterial forces. It’s all about stress; if you don’t let the bacteria relieve the stress in its DNA, it cannot function.  I feel like there’s a life lesson in there, somewhere.

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5 thoughts on “How Drugs Work: Antibiotics Part III

  1. Pingback: How Drugs Work: Antibiotics Part III | Science Communication Blog Network

  2. Gyrase being cast in a role of a massage therapist is just one of the reasons I adore your posts, Katie! They are what I hope to find upon receiving an e-mail nowadays. Keep it up, your presentation is wonderful!

  3. Pingback: The Week In Science (Mar 11 – 17) | Science Communication Blog Network

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