“Bristol is at the centre of the fight against antibiotic resistance.”
Antibiotic resistance is as grave a threat as climate change, but it gets nowhere near the amount of media attention (and the conflicting terminology doesn’t help). Modern life relies on antibiotics, the drugs used to treat bacterial infections. But bacteria are evolving resistance to antibiotics, making the infections they cause harder to treat and putting global security at risk.
In this article, we’ll look at four Bristol innovators working on tech designed to beat the bad bugs. From ‘making bacteria self-digest’ to ‘molecular tyre shredders’, we will cover the latest tech being developed in Bristol.
In 2013, the UK Government recommended ten actions to tackle antibiotic resistance on the supply and demand sides. Some involve regulation or raising awareness of the issue, but others clearly require technological innovation. That’s where science entrepreneurs are needed.
The economic burden of developing new antibiotics is too great for small companies. Bold startups are addressing this crisis head on, by developing technologies to reduce the demand for the antibiotics we do have, making sure that they remain effective. Bristol is a hub of activity for research into antibiotic resistance. Below, we’ll examine four innovators in the region, all hoping to reduce the demand for antibiotics.
“Antibiotic resistance is a complex problem, one that calls for collaboration between scientists, doctors and entrepreneurs. Bristol is a centre of excellence for research in this space, and a real melting pot. We’re a creative city, and you can see that in the range of solutions our scientists are pursuing.”
1. Folium Science
Making bacteria self-digest
Agriculture is the biggest consumer of antibiotics. In the USA over 70% of antibiotics important for human medicine are given to livestock. Up to 90% of these drugs pass straight through animals unchanged. Farm wastewater is used for irrigation, and manure as fertiliser, which spreads antibiotics throughout the environment, where they drive resistance in bacteria.
The use of sub-therapeutic antibiotics in animal production is becoming increasingly restricted across the world and consumers are rejecting meat produced using antibiotics. This means that the industry is looking for effective alternatives that will prevent the spread of undesirable gut bacteria, promote animal health, and reduce human zoonosis (disease crossover from animals into humans). Currently, the range of options available to producers are not fully effective in removing unwanted bacteria.
Many countries have now banned the use of antibiotics as growth promoters in animals, however in countries where their use is still permitted, this will contribute to an increased risk of antibiotic resistance in bacteria. By selectively removing unwanted bacteria, Folium’s patented ‘Guided Biotics’® could reduce the need for antibiotics in agriculture. The technology harnesses the natural CRISPR-Cas9 system.
Some bacteria use a nuclease enzyme (Cas) to cut the DNA of attacking organisms. Guided Biotics redirect this mechanism so that undesirable bacteria cut their own DNA. This causes unwanted bacteria to self-digest, specifically removing them and leaving ‘good’ bacteria intact. Although CRISPR is more widely known as a gene editing tool, the action of Guided Biotics does not involve any gene editing of the target bacteria.
Folium Science’s Guided Biotics technology has many advantages, as shown in the table below. Folium was founded in 2016. They’ve already proved that their technology works in five independent studies.
“At Folium Science, we’ve pioneered a platform that can reduce the need to use antibiotics in agriculture. Guided Biotics are selective and precise, will promote animal wellbeing and performance and reduce the risks of resistance. We’ve proved that our technology works: now it’s time to take it to market.”
Because Guided Biotics can be designed to selectively remove many different species of bacteria, Folium Science are applying their technology to bacteria that cause diseases in important animals and plants. Folium’s priority targets for poultry are Salmonella, pathogenic E. coli and C. perfringens. They are also developing products for other zoonotic, spoilage and wastage bacteria.
In July 2020, the company won an Innovate UK grant to develop a treatment for Xanthomonas bacteria that devastate staple crops such as cassava, rice, and soy. Folium Science is working in partnership with the John Innes Centre to develop crop protection products for use on fresh fruit and vegetables and broad acre crops. They aim to reduce crop losses and boost overall performance by promoting a productive microbiome. Folium will launch their first product, targeting Salmonella in poultry, in 2021.
Detecting bacteria with fluorescent velcro
Urinary Tract Infections present an unrelenting burden on public health as one of the most common bacterial infections, with an estimated 150 million cases per year reported worldwide. UTI’s are the second highest cause of antibiotic prescription and many patients will receive an empirical antibiotic treatment without confirmation of bacterial infection.
FluoretiQ are developing NANOPLEX™ technology for rapid identification of bacterial infections. This technology can reduce bacterial identification from 48-72 hours to under 15 minutes, delivering the sensitivity of the lab at the speed and convenience of the dipstick.
When you have a bacterial infection, bacteria must find a way to attach themselves to their human host. They do so in a very similar way to Velcro, bacterial ‘hooks’ recognise human ‘loops’ and adhere to the surface of cells to establish the infection.
FluoretiQ are exploiting this interaction in reverse – by mimicking these ‘loops’ on the surface of human cells their probes can recognise bacteria ‘hooks’ allowing for their identification in clinical urine samples.
The technology combines two parts. The first element is a fluorescent nanomaterial probe engineered to recognise one bacterial species over another. The second element is a Quantum-enhanced detection module that allows fluorescent detection without the need for incubation or amplification of the bacterial signal.
The result is a fluorescent readout that confirms if bacteria is present, which kind, and how many, all within 15 minutes.
The approach has three steps:
A patient sample is mixed with probes that target specific bacteria.
1. Probe-labelled bacteria are separated from unlabelled species.
2. Bacteria bound to probes are measured by Quantum-enhanced fluorescent detection.
3. Nanoplex will identify 90% of uropathogenic bacteria in urinary tract infections and is undergoing development with clinical samples at regional pathology laboratories.
“Even with new drugs under development, the only way to safeguard the future is to develop the right diagnostic tools to allow us to quickly identify bacteria at the point of consultation. Nanoplex can offer this information to the physician at the point of care, reducing the need for empirical antibiotic use.”
FluoretiQ are currently focused on urinary tract infections, but plan to expand their focus to a wider range of infectious disease areas. Product development is well underway and FluoretiQ hope to launch their first product in late 2021.
3. The Su Group
Molecular tyre shredders
Surgeons use titanium implants to replace joints and repair bones because of its strength and because the body doesn’t reject it. Unfortunately, bacteria attach themselves to these implants and multiply. These bacteria quickly form a biofilm by producing a sticky goop of proteins and carbohydrates. Bacteria in biofilms start working together to survive, protecting themselves from the immune system and antibiotics. These bacteria cause inflammation around the implant, destroy tissue, and spread throughout the body, causing serious infections.
The only way to treat these infections is to surgically remove the implant and put the patient on a long course of strong antibiotics. This problem increases the demand for antibiotics and the risk of resistance. In the UK, there are nearly 800,000 hip replacements every year. Up to 17.5% get infected and fail, each costing £25,000 on average.
Rather than relying on antibiotics, Professor Su’s group at the University of Bristol have taken inspiration from nature. Cicadas have evolved a way to keep their wings clean from bacteria that might infect them. Their wings are covered with tiny spikes which pierce bacterial cells, killing them within three minutes.
Professor Su’s group have developed a process for coating the surface of titanium with similar spikes. They designed two patterns:
• Spears – densely packed short spikes similar to the cicada’s wing
• Pockets – longer spikes which twist together into larger pockets
The researchers tested their designs against polished titanium to see if they could kill bacteria that tried to grow on the surfaces. Bacteria found it more difficult to attach themselves to the spear pattern, and the first wave that did were pierced and killed. But a layer of dead cells built up on which new bacteria could grow and form a biofilm.
However, the pocket pattern was more effective. Bacteria initially adhered to the rims of the pockets, which are blunt. As they divided, they pushed each other into the pockets, where they were either pierced by or squeezed between the longer spikes. The dead cells in the pockets decayed before new cells could grow on them. After six days, five times fewer bacteria were seen on the pocket-patterned surface compared to polished titanium, and half of those cells were dead.
Professor Su’s group are continuing to work on a variety of antibacterial surfaces. Their designs need to be refined, but if they reach the clinic, they could make implants much safer, and stop antibiotics from being wasted. Professor Su says: ‘Antibiotic resistance is a complex problem, one that calls for collaboration – between scientists, doctors and entrepreneurs.’
“Bristol is a centre of excellence for research in this space, and a real melting pot. We’re a creative city, and you can see that in the range of solutions our scientists are pursuing.”
Fighting Antibiotic Resistance in Bristol
Bristol is at the centre of the fight against antibiotic resistance.
The city boasts:
• Internationally-renowned universities producing world-class antibiotic resistance research.
• Innovative spin-out and start-up companies with bold ideas to solve the problem.
• A network of science and technology incubators to help these companies grow and bring their technologies to market.