What are bacteriocins and how can we harness their therapeutic potential?

Antimicrobial resistance (AMR) is one of the biggest threats to global public health, mobilizing researchers and companies to explore non-traditional avenues for treating bacterial infections. Among them is Glox Therapeutics (Glasgow & Oxford, UK) – a company developing precision antibiotics from naturally occurring bacteriocins. Back in February, Glox Therapeutics appointed Michael Murray (left) as Chair of the Board to help guide the commercialization of their precision antibiotic technology. Michael has extensive experience in the biotech and pharma industries. Since 2009, he has been the Principal at Murray International Partners (Edinburgh, UK), where he supports life science companies with commercialization, including intellectual property management, market assessment and deal making. We caught up with Michael to learn more about Glox Therapeutics’ technology and their commercialization journey. What are bacteriocins? Bacteriocins are specialized small protein elements that bacteria naturally produce and release into the environment around them to ward off other bacteria. For example, think of a type of Pseudomonas bacterium that’s competing for a space in a hospitable niche alongside another Pseudomonas-like bacterium. Bacteria have evolved a proteinaceous element that is extruded from the cell and works as a highly specific antibiotic against target bacteria, unlike broad-spectrum antibiotics such as penicillin or amoxicillin. How have Glox Therapeutics harnessed bacteriocins? Dan Walker, one of the co-founders of Glox, studied bacteriocins with Colin Kleanthous in the Department of Biochemistry at the University of Oxford. Here, he recognized the potential therapeutic application of the bacteriocins. At Glox, they aim to amplify what happens in nature by grouping naturally occurring bacteriocins to form potent therapeutics. These days, when you look at an infection, you'll find that there are several subspecies of Pseudomonas present as well as other bacteria, such as Escherichia coli or Klebsiella. Therefore, although bacteriocins offer much needed specificity, we need to alter them so that they can target a slightly broader range of bacteria, while remaining narrow-spectrum, precision antibiotics. The team at Glox alter them using classic molecular biology techniques partnered with innovative biotechnology, which involves expressing bacteriocins in a plasmid and allowing them to self-assemble. What challenges has the team faced as they develop these novel precision antibiotics, both scientifically and industrially? Let's start with the science. If you take a bacteriocin from one genomic environment – from one species – and try to express it in another, you can anticipate some difficulties. In nature, bacteria encode an immune protectant element in their bacteriocin construct, which shields the bacterium from the worst effects of the nasty little peptide it just released to go and kill its neighbors. However, when you express a bacteriocin in a different species to the one it was developed in, the protein could be killing the cell in which its being expressed. Once you start expanding your repertoire of different bacteriocins, you must be mindful that each of them may be toxifying the very cell system you're using to make and amplify them. Another challenge is that you must know the different mechanisms bacteriocins use to enter cells so that you can engineer your construct to increase the odds that it will still be amenable to its uptake route. A challenge that many therapeutics companies will encounter is unless you can make large and pure amounts of any biologically active agent, you won't have a chance of making it into a product. The team at Glox is getting high yields, over 30 micrograms per liter, without even optimizing all the growth factors yet. This is encouraging; they're getting significant expression levels with very high purity. In terms of industry challenges, sometimes there's a bit of education required before you can focus on the main topic. Bacteriocins aren’t prominent in industry, and therefore it can be difficult to convince companies to get on board. Pharmaceutical companies will tell you they want something dazzlingly new and never done before. Then when you go to them with it, they say, “This has never been done before. It's going to cause us a problem when we go to regulators.” Building a company and having it not fail is so important. There is some outstanding science out there that's never going to make it – not in Glox’s case – because there isn't a good management team, or investors don't quite get it, or the scientists themselves cannot communicate it effectively. Why did you join as chair of the board? There is so much fascinating work being done in drug development that it can be hard to decide which projects to get involved with. However, when I met Glox CEO, James Clark, and Co-Founder, Dan Walker, I could tell they were doing something really special. They are extremely focused and driven, with high-quality science at the center of everything they do. Additionally, from a commercial point of view, their precision antibiotics have an obvious place in the treatment pathway for patients. Tell us about Glox’s recent funding awards. Glox has been awarded substantial funding from sector-leading investors, which is a clear and enthusiastic vote of confidence for the company and the work that they’re doing. The way that money has been deployed into the company has been quite typical; an investor says they’ll give you X million, which usually means that they’ll give you X million minus Y million to start with, and as long as you don't do anything silly with it, the rest will follow based on milestones reached. Glox is working on an aggressive series of milestones, and they haven't met them. They've exceeded them. Momentum is the key for small startups growing into small and medium-sized enterprises (SMEs). Glox continues to build momentum; they were given one of the prestigious PACE awards by LifeArc (London, UK), Innovate UK (Swindon, UK) and Medicines Discovery Catapult (Cheshire, UK). I think they had over 130 high-quality applications. Five awards were made, and Glox was one of them. The award is more than just money, it comes with additional expertise in the form of access to world-class leaders in the fields of antibiotics, antimicrobial medicine and antimicrobial industry. The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of BioTechniques or Taylor & Francis Group. The post What are bacteriocins and how can we harness their therapeutic potential? appeared first on BioTechniques.