Giving germs a cold of their own

05 December 2016

Interview with

Professor Martha Clokie, University of Leicester

Part of the problem of antibiotic resistance lies in the fact that these bacteria evolve resistance to our drugs. But what if you could have an antimicrobial agent that evolves with the bacterium so that, no matter how many clever tactics the bacterium develops, the treatment will stay in step and keep on killing it? This is what the University of Leicester's Martha Clokie has been working on. She's using viruses that selectively attack bacteria - these are called bacteriophages - to tackle hospital superbugs and she told Graihagh Jackson about her work...

Martha - Bacteria have got natural viruses that infect them. So in the same way that we have, for example, flu and ebola viruses that attack humans, bacteria have got their own natural enemies in the form of viruses that target and kill them.

Graihagh - How do they do that?

Martha - They attach and then they inject their DNA into that bacterial cell. They turn that bacterial essentially into a virus factory and then they pop out and maybe a hundred viruses will be released and then specifically go and infect other members of that same bacterial species.

Graihagh - Sounds like a lovely way to die. Why is this virus better than using antibiotics then?

Martha - Well, as I said, viruses are also natural enemies of bacteria. Your guest, he was talking about how antibiotics are part of this bacteria-bacteria warfare, and that's really been fairly well characterised. But this interaction between the viruses is much less known. And one real advantage that the viruses have, which in a way makes them quite difficult to study is that they're very, very specific. As you said, I'm working with superbugs, Clostridium difficile, and viruses that will infect them won't infect other bacteria that are in us and on us.

Graihagh - I know there are multiple strains of things like C. diff, so  would you need one virus to kill them all? How specific are you talking?

Martha - Yeah. So they're specific within a species and also within a subset. So with Clostridium difficile there's over 450 different types. But generally, if you look at any one hospital at a time you will find there's perhaps twelve strains circulating. Just four viruses, actually, within Clostridium difficile are enough to be able to kill 90 percent of all of the strains that are commonly found, so you do need a number of viruses.

Graihagh - That's pretty good going. So the other thing I know that's really important about when you're using a virus is biofilms, the things that bacteria create to stick to where we get infected, and I know that your viruses are actually taking away that. But what's the benefit of this technique?

Martha - One is the fact that they're so specific. If you take a virus, if you've got that hospital superbug, Clostridium difficile, and I give you a set of viruses, I will just remove that one species, not the others. So often, when we take antibiotics, they make us feel very groggy because they kill lots of bacteria that are performing useful functions on us. So it's a sort of selective sharpshooter, the removal of that one pathogen.

Graihagh - And how do you envisage just taking this - like a pill?

Martha - Well, yes, exactly. I'm working with my collaborators at the University of Loughborough and we've shown that we can encapsulate these viruses into a pH-sensitive polymer so we can take them the same as you take an antibiotic. So you'd take this pill full of viruses and then get through that acidic stomach, because viruses don't survive well in those acidic conditions, so you've got to get them through the stomach into the area where Clostridium is causing the infection.

Graihagh - And there's no danger of us being infected by this virus as well, is there?

Martha - No, absolutely not. The viruses need very specific proteins on the surface of the receptors to hook onto so there's no way that they could jump from a bacteria to a human. Even, as I say, within the bacterial species they're pretty selective.

Graihagh - Awesome! So Martha, you were on the show three years ago - how has your research progressed since then?

Martha - Yes, it gone really well. I think about three years ago, we had a set of viruses and I was able to tell you yes, our viruses look like they kill the right kind of thing. And now I can tell you yes, we only need four and it's useful having these four because they kill in different ways. And the advantage of that is that we really minimise resistance.

The other thing that we've done is designed lots of different complicated models to mimic how the virus kills us. So we can create them on artificial guts and epithelial cells, and whole bunch of different, more complicated insect and other models and we've shown that the viruses work really well in those different models.

Graihagh - That sounds really exciting. Very briefly, you know the question I'm going to ask you. When are we going to be seeing this in the clinic or is it there already?

Martha - Well, there are clinical trials that are currently going on with other drugs at the moment. There's an EU project that's doing a study and there's another one in the States and Australia. So we're seeing clinical trials now for the first time as a revival of those. You can have them in the clinic in some countries, Russia or Georgia, but we're cottoning on to the fact that we need to use them in the West and clinical trials are finally starting to happen.

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