Folium Science are a biotechnology-based company with a novel system (called Guided Biotics™) set to be an alternative to antibiotics. Chief Executive and Co-founder Ed Fuchs and Chief Scientific Officer Martin Woodward joined Anna Fleming to discuss their entirely new approach to tackling the challenge of antibiotic resistance.
So what is Folium’s technology?
Martin: One of the biggest problems the world is facing right now is antibiotic resistance. It’s getting harder and harder to find new antibiotics, and our existing antibiotics are coming up against pathogens which are highly resistant. Even when antibiotics are effective, they’re far from perfect. They’ll kill the bacterium you want, but they’re non-specific – they’ll damage the gut flora, which often causes antibiotic-associated diarrhoea while the gut flora re-stabilises. Folium has a completely novel way of selectively removing unwanted organisms including those that are antibiotic resistant. We’re focusing on bacteria in animals, because there are a lot of pathogens of animals that are highly resistant thanks to antibiotic overuse, and there are no new treatments out there.
Ed: There was a recent study on avian pathogenic E. coli, where it was found that 90% were resistant to at least one antibiotic, and 50% were resistant to at least 3 from completely different groups of antibiotics.
Martin: It’s getting into superbug territory.
Ed: I am a believer in dealing with the root cause rather than treating symptoms or outbreaks. By caring for these animals and maintaining their health, we can improve their overall welfare.
How does it work?
Martin: Bacteria can get infected by viruses and so they’ve developed a primitive immune system. They capture some DNA from those invading viruses, and they use that as a target. So if the virus invades again the bacterium recognises it and uses an enzyme to cut the DNA. When the viral DNA is cut, that virus is no longer viable and cannot cause the infection.
Let’s take Salmonella as an example. We get a lot of Salmonellosis in animal production, and it’s also a pathogen in humans. We’ve looked at Salmonella DNA and identified fragments which are unique to the species. So when we introduce these fragments in the right sequence they trigger enzymes to cut the same unique sequences in the Salmonella’s own DNA, meaning it’s no longer viable. It kills the bacterium, very selectively, and very efficiently.
So how does it get delivered?
Ed: We either use specific viruses of bacteria, or friendly bacteria (probiotics). Both have different benefits and different challenges to overcome.
Martin: The virus method involves taking a virus that’s specific for bacteria, and then placing the target DNA sequences into it. So when the virus binds the bacterium, it injects our DNA target and that triggers the cutting process.
Our second method involves a process called conjugation that bacteria use to pass DNA between themselves. They basically make a bridge between their cells and transfer short loops of DNA, called plasmids. We place our target into a plasmid, and add it to a benign strain, like a probiotic. When conjugation happens, our DNA will move into other strains. When it ends up in Salmonella, exactly the same story.
Ed: That’s actually how lots of antimicrobial resistance genes have been transferred, and now we’re using the same mechanisms to transfer our Guided Biotic.
Martin: We’ve put that system into chickens and our data shows we can control Salmonella. When the probiotic Guided Biotic is given to the chickens it gives massive and very statistically significant protection. And, what’s more, because it’s so rapid, and because it uses multiple targets, the chance of Salmonella mutating to develop resistance is 10-23. It’s negligibly low.
Ed: It also reduces the risk to humans – if the Salmonella isn’t controlled, this nasty pathogen is shed into the environment, which means potential re-infection at a later stage of life. You then take that risk with you into a production environment. We can reduce that risk 3-5 fold, which is very, very significant.
Amazing. So how did Folium start?
Ed: A good friend showed me the technology over a glass of wine one Christmas. I’m not a biologist; I’m an engineer, so I said ‘What are you talking about?’ After the second glass of wine I said ‘Wow, that’s phenomenal!’ I took the file and did some research. It became clear early on that the antimicrobial resistance challenge was something we could address. That’s when I approached Martin.
Martin: I’d been aware of the technology, but having the intellectual property rights tied to Folium was the starting point. It was already protected – it was a no-brainer, really. There are so many applications – we could apply it to cows’ udders to stop mastitis, we could put it in a foot dip so that when farmers go in and out of their sheds they disinfect. You could spray it on abattoir walls, even on a knife, on a work-surface, use it to coat wrappers in the food industry. That’s all aside from all of animal rearing. And then there’s the human health side too. I’ve been in veterinary microbiology for 40 years now, but when I saw this I was very excited. So we got together.
And since then?
Ed: We’ve put together the science plan and built up the team. We’re now a team of 10 full time employees, nearly 25 people including consultants and associates. We’ve been invested in by the Lundbeck Foundation from Denmark. We’ve got proof of product in Salmonella, we’re now working on Campylobacter, hopefully moving into trials later this year. The UK government has been extremely helpful; we’ve been awarded three major Innovate UK grants. We’re working with major strategic animal feed additives businesses worldwide and hopefully we’ll do a deal very shortly.
So where do you see Folium going?
Ed: With a probiotic delivered solution you can create product plans that are specific to the species that’s having the challenge. We can target bacteria that are associated with a certain life-stage of a chicken or a cow, a fish, or even a plant. We’re working on tomatoes and will be tackling soft rot in Brassicas shortly. You can see a highly saleable product range starting to develop. Within the next year or so I’d like to get this Salmonella product into market in South-East Asia and generate revenue for the business to develop as we take it into the US and European markets.
You were based at Cambridge before moving here – why Bristol? Why Unit DX?
Ed: Well, this was an area that the team wanted to be, it a vibrant city that offers a lot for a young team and business such as ours.
Martin: It’s vital that we have the capability to do what we need to, scientifically. And Bristol University has been superb. They directed us here, which is a great environment; there’s a real can-do attitude.
Ed: There’s a great scientific ecosystem here which has really helped us. Whilst it’s taken a while to set up from a biological perspective, it’s a perfect starting point, and a launch-pad for our research.
Find out more about Folium Science at their website.