Breakthroughs in antibiotic resistance

25 September 2014

Interview with

David Walker, UK Deputy Chief Medical Officer, Michael McArthur, Procarta Biosystems, Ewan Harrison, University of Cambridge, Vanya Gant, UCL

According to the government's chief medical officer, Dame Sally Davies, the danger posed by bacteria becoming resistant to antibiotics should be ranked along An assortment of drugswith terrorism on a list of threats to the nation. We need to tackle this problem head-on by creating new antibiotic drugs, by using the ones we got more carefully, and developing new strategies to stop superbugs taking hold in the first place. This was the message at a conference in Cambridge entitled "one bug one drug".

Representatives of pharmaceutical companies and drug discovery ventures got together to develop a plan of action. Chris Smith went along to meet some of them to hear about the approaches they're taking. Dame Sally Davies wasn't there this time, but her deputy, David Walker, was...

David - We're facing a very important problem here. Progressively, bacteria are becoming resistant to antibiotics. Over the last 20 years, we've seen a decline in the production of new antibiotics and so we face a problem in that we are having fewer and fewer antibiotics to treat more and more infections.

Chris - And if we take this to its logical conclusion, what's the end of the story?

David - Well, if we're not able to produce a steady supply of new antibiotic products, then more and more infections are going to become more difficult to treat and some of the more conventional procedures we use in medicine are going to become much more risky. Things like transplantation, joint replacements, and of course, the treatment of classical infections will become very difficult.

Chris - Is there any evidence that this is actually happening?

David - Yes. Well, we are seeing increasing numbers of infections by resistant organisms and these not only have worse outcomes, they're also much more expensive to treat.

Chris - Let's talk to a group of people who are actually working on pioneering the next generation of treatments to address the issues that David's raised.

Michael - I'm Michael McArthur, Procarta Biosystems. What we're trying to develop is a new class of antibacterials. We do this by taking small fragments of the bacteria's own DNA and these bind to key proteins called transcription factors that control gene expression. Without that ability, they're unable to cause disease and they rapidly die.

Chris - So in a normal bacterial cell, they will make these chemicals called transcription factors which go on to their DNA and turn genes on and off that the bacteria needs to control. You're saying if you put in bits of the bacterial DNA artificially, they could, what, soak up all these transcription factors so they don't go where they're supposed to and this is going to disrupt the ability of the bacteria to control themselves.

Michael - That's right. It's a very simple approach.

Chris - This means then that because you know what the genetic sequence of the bug you want to treat is, you could make little pieces of DNA, which means that they will exclusively target that microorganism, which would leave the good bacteria in the body untouched.

Michael - That's right, yes. We can develop bespoke antibacterials with a very narrow and defined spectrum.

Chris - Where are you with this? Is it ready to go?

Michael - So, we're in the process of taking things into animal models. So that puts us about four or five years out from what we'd hope would be successful clinical trials.

Ewan - My name is Ewan Harrison and I'm a researcher in the Department of Veterinary Medicine in the University of Cambridge. We're working on MRSA, which is Methicillin- resistant Staphylococcus aureus. One form is a hospital super bug that's caused massive problems. We're also interested in this because there are some kinds of MRSA that now are starting to become a problem, particularly in continental Europe, and we think this is coming from animal populations, in particular, pigs. We're working using genomics, so this is sequencing  the DNA of the bacteria to look at how the bacteria is moving from animal populations into people, and so to do this, we construct a family tree of bacteria and we look for the direction that we think that the bacteria are moving.

Vanya - Hello, I'm Vanya Gant. I'm consultant microbiologist at UCLH in London. I'm leading a group to develop some diagnostics whereby you can find those antibiotic-resistant bugs more quickly, but my other interest which I think really, really does need to be followed up relates to probiotics. These are the so-called good bacteria and they live in our bowels and one of the things they do is they keep the bad bacteria out. I have a very strong suspicion that it might be possible to keep the bad bacteria out by feeding people large amounts of probiotics.

Chris - This will outcompete the bad guys but only in the intestines, surely, if one of your patients is already got an infection in their brain or in their chest, you can feed them all the bugs that you like but it's not going to treat their chest infection.

Vanya - Yes, that's true, but in my field of work, I'd say well over three quarters of the life-threatening infections arise from those bugs that live in the intestines and when you haven't got any immunity they then end up in the blood, and the brain, and wherever else they can cause trouble.

Chris - Have you got a strategy that will enable us to do this?

Vanya - Well, yes, I have got a strategy. The big problem with probiotics is that 98% of them, as you buy them over the counter, just do not work.

Chris - Because you eat them. They go into your stomach, the acid kills them and they don't actually ever end up in your intestines to do you any good. So, people are wasting their money effectively, aren't they?

Vanya - That's exactly right. I know of one or possibly only two compounds in liquid form in this country that survive stomach acid and actually do what they say on the tin. We have to do a proper trial whereby half the patients get the probiotics and the other half don't, and we have a look for positive health benefits in terms of controlling antibiotic resistance and possibly even being able to get rid of the bad bugs that have set up home in these patient's intestines.

Chris - UCL's Vanya Gant with what sounds like pretty damning indictments of most probiotics.

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