Before we get to the topic of Bacteriophages, we should look at the work of microbe hunters like Hazel Barton.
Professor Hazel Barton
It’s a hunt that has taken Professor Hazel Barton across the globe.
Hazel Barton “I get to travel the world, I get to see amazing things, so I just love it!”
You might think that new antibiotics were created in a lab, or discovered deep in the rainforest, but actually most of them have been found in the dirt.
Professor Hazel Barton “Almost all of the antibiotics that we use now have come from soil micro-organisms. The procedures that we have in the lab for finding antibiotics is literally to pull the microbes out of this and grow them.”
More than three-quarters of the antibiotics we regularly use in hospitals today were taken from microbes in the soil.
Professor Hazel Barton “And the trouble is, we’ve been doing that for 50 years and we keep finding the same things.”
And the best microbes for producing antibiotics are bacteria themselves. To find a new antibiotics, Professor Barton has to hunt down new bacteria in some of the most untouched places on Earth. Hundreds of metres underground.
For bacteria these caves are one of the toughest places in the world to survive.
These caves may look peaceful and still, but they are, in fact, a battlefield. With so few resources available, bacteria must fight each other to survive.
Hazel Barton “Between where we’re standing right now and the surface, there is about 1,000 feet of rock. So for anything that’s happening on the surface, all that energy from plants and animals, for that to come here, it has to get through all that rock, and it can’t do that very easily. So we end up with this very starved environment, where there is hardly any energy available.”
Hazel Barton “They become either much more careful of their resources in defending them, or they get more aggressive in stealing someone else’s resources.”
They do this by producing an arsenal of chemical weapons. Professor Hazel Barton has been collecting these weapons in the hope they might be used as antibiotics. Last year, she captured one type of bacteria that produced over 38 different bacteria-killing chemicals.
Hazel Barton “To put that in perspective, there is only about 40 antimicrobial drugs in the clinic right now. So one bug from this cave was able to make almost as many as we have available to us in the clinic. Not all of those are going to be useful as medicines, but the potential becomes huge. I mean, we’ve pulled out 4000 microbes, so it’s almost like a chemical universe and we are kind of playing on the edges of it with antimicrobial compounds and there’s this huge vast unknown space that we’ve yet to kind of explore to see what’s out there.”
The work of scientists like Professor Hazel Barton is becoming increasingly important, as any new antibiotic discovery will enable us to retain our hold over the superbugs.
But eventually, bacteria will always find a way to become resistant to even the new antibiotics. If we are going to finally overcome the problem of resistance we are going to need a whole new approach.
Dr David Harper
On the face of it, this seems an unlikely place to discover a new strategy for fighting superbugs. It’s a sewage works in Buckinghamshire. But microbiologist Dr David Harper believes the answer may be found here. He’s hoping to exploit the weapons technology of a creature that has developed its own way to fight bacteria.
David Harper “Bacteria have been on the Earth for billions of years. That’s why they’re so tricky. But there is something else that’s been on the Earth for billions of years. And it knows how to deal with bacteria. That’s what I’m here to collect.”
Raw sewage is the perfect breeding ground for bacteria. But that also makes it the ideal home for the ultimate bacterial predator. He wants to enlist that predator to fight for us in the superbug war.
David Harper “In this bottle, although we can’t see it, there is a war going on. There are billions of bacteria struggling for existence, and tens of billions of bacteriophages. Viruses that only and specifically affect and kill bacteria. And they are fighting in there, as we speak.”
Just like humans, bacteria can be infected and killed by viruses. bacteriophages are the most common and diverse predators on earth.
David Harper “There are 10,000 billion, billion, billion, bacteriophages on the planet. We haven’t actually counted, that is an estimate.”
Dr David Harper wants to get these bacterial viruses fighting on our side in the superbug war. “bacteriophage” literally means “bacteria eater”. They work by landing on the bacteria, injecting in their own DNA, then reproducing themselves inside the bacteria until it bursts. Back in his company’s lab, Dr Harper is attempting to harness the power of these bacterial predators. It’s a tricky business. To kill disease-causing bacteria, you need the particular phage which attacks that bacteria species.
David Harper “We go and collect the sewage, and bring it back here, we put the sewage into a culture of the target bacterial species. There are lots of different phages in there, I said there were billions. There are, maybe thousands, maybe hundreds, that will hit this particular species. In a few cases, you might have a species where only a few will hit it, but still, if they’re there, they will bind, they will kill, they will multiply and you can pick them and grow them.”
Using viruses to kill bacteria sounds like an attractive idea in principle, but in practice, working with live organisms has proven difficult. But Dr David Harper is drawn to this field of research because phages offer one significant advantage over antibiotics.
David Harper “Antibiotics can’t change. If the bacteria generate resistance, that’s it, you need a new antibiotic. With phages, the bacteria are their lunch. If they can’t multiply, they die out. If they can, they grow. So when bacteria change, a few phages will be in there, which can grow in the new ones. That mutation is then preferred, those phages will multiply and come to dominate. The bacteria will change again, a few of those will be able to grow, they grow again, they amplify, they come to dominate. It’s an arms race.”
Tapping into this arms race would hand us the key advantage because the bacteriophages are able to evolve. If we are able to enlist them to fight for us, they will keep fighting for us, even as the bacteria change.
David Harper “They are in many ways a perfect drug, in many ways they aren’t. One of the most telling things against bacteriophages as drugs is that nobody has yet developed one.”
Dr Harper’s company have seen some early successes and are now planning a trial to treat lung infections often affecting cystic fibrosis sufferers.
David Harper “We hope that the results in cystic fibrosis will be convincing. We hope to move on to the large clinical trials of hundreds of patients, which will underpin progressing this to market to improve people’s lives, to save people’s lives. There’s a long way still to go, but we’re working on it.”
Right now, phage medicines are still in the very early stages but new developments in understanding exactly how bacteria become deadly and giving hope that there could be another way to outsmart them.
Bacteriophage – Wikipedia Page