Preventing antibiotic resistance

Rapid DNA-sequencing technology can be used to identify quickly the bacteria responsible for causing an infection, meaning that narrow-spectrum targeted drug treatments, with inevitably fewer side effects, can be administered to patients, as John Wain, Professor of Microbiology at the University of East Anglia, explains to Kat Arney...

Kat -   How are bacterial infections currently identified and how long does that take?

John -   So, the identification currently is through culture at the microbiology lab.  So, we actually have to grow them.  Some people call it chemical gardening, but it's a matter of days before we can actually get a result.  What that means is that when you go to the GP, the doctor has given you antibiotics on clinical grounds.  So, they take a look at you, decide if you've got an infection or not and then the decision to actually give antibiotics is taken and then the samples are taken and the diagnostic results come back.

Kat -   So, it's a bit of a shooting in the dark approach and if you get the wrong one to start with, it could be really serious.

John -   That's why this idea of broad spectrum antibiotics tends to be quite popular.  So obviously, if you're - as you put it - shooting in the dark then you want something very broad so that you make sure that you kill what it is that you are actually shooting at.

Kat -   So, how are we using new genetic techniques to actually try and get down to a precision rifle at these bugs?

John -   Okay, so obviously there are problems with using broad spectrum. There's the problem of collateral damage as we heard with the Clostridium difficile - if you interfere with the gut flora, you're likely to get overgrowth of a pathogen.  So, this specific idea is that we just get the pathogen and we don't hit the normal flora.  So, there are two ways that we can overcome that.  The first is, with good diagnostics and that's where these new technologies in sequencing can really help.  So, we've heard about being able to recognise the microbiome.  You can also recognise the pathogens that are causing infection if you take the right samples, and if you can get that sequencing out quickly enough then you can get a real-time evidence in so that you can actually use targeted antibiotics.

Kat -   And how quickly are we talking about and how quickly could we do that nowadays and how quickly do you think it will become possible in the future?

John -   The quickest we could do it at the moment is we can do two large scale sequencing runs a day. 24 to 48 hours realistically is the quickest you can do it at the moment.  But that's on a large machine which is laboratory based.  There are new technologies coming out which look sort of USB sticks that you put into a computer.  Those will, I believe in the not too distant future, be giving us results much more quickly.

Kat -   So, that's something that's really positive.  But then what can we do with this information that can actually make treatment more effective and particularly overcome this problem of resistance?

John -   So, the other problem to using targeted antibiotics is developing targeted antibiotics.  So, there are lots of chemicals out there, lots of small molecules, lot of compounds that hit bacteria.  So, we know we can kill this bacteria, but the problem is, taking those hits to what the chemist call hit optimisation.  So, choosing which of those chemical compounds to actually take forward.  Then using high throughput sequencing technologies, we can now X-ray a bacterium, we can look right inside that bacterium and actually work out exactly what these small molecules are doing.  That allows the chemists to optimise them more effectively so that we can choose which ones to put into lead op.

Kat -   I guess it's a lot similar way to the kind of targeted therapies in cancer that we're seeing nowadays isn't it?

John -   Yes, it is very much so.  It's also obviously has similarities with what we're hearing about with the bacteriophage therapies.