Martha Clokie, Professor of Microbiology at the Becky Mayer Centre for Phage Research, explains how the Becky Mayer Centre is using revolutionary phage therapy to tackle the global crisis of AMR.
Humans are increasingly suffering from bacterial infections that no longer respond to antibiotics. This crisis also affects pets and food animals, intensifying the threat to our health. This global crisis, known as antimicrobial resistance (AMR), is one of the most urgent threats to human and animal health. Without new solutions, even minor infections or routine surgeries could once again become life-threatening.
There is hope, however, in the form of bacteriophages (often shortened to phages). The word ‘phage’ comes from the Greek for ‘to eat’ because phages are viruses that kill bacteria, so appear to eat them. Just like us, bacteria also have viruses that infect them, and, similar to animal viruses, phages are generally specific to particular types of bacteria.
Phages can be used to treat people with infections. They can be developed as a targeted and sustainable solution to AMR. Using phages as treatments like this is termed ‘phage therapy’. Until recently, therapeutic phage development was seen as being complex and unnecessary as we had antibiotics. It has been difficult, therefore, to get funding for essential groundwork needed to make phages mainstream.
Although the resource for phage research accounts for a small fraction of AMR funding, it is now widely acknowledged that phages could be a key part of the AMR solution. I summarise the work taking place at our Becky Mayer Centre for Phage Research (BMCPR) at the University of Leicester, and show how, by bringing together traditional knowledge and cutting-edge science, we can unlock the full potential of phage therapy for an antibiotic-resistant world.
I also share highlights of our international collaborations through the PhageCompass, reflecting on our recently awarded European grant from the Joint Program Initiative for Antimicrobial Resistance (JPIAMR), and explore our involvement with the not-for-profit Phages for Global Health, which extends our reach worldwide. I outline how we aim to position the UK as a global leader in the fight against AMR by bringing together a critical mass of phage expertise, amplifying the strong UK research base and accelerating international phage development through shared knowledge and co-ordinated action.
Where do you find phages?
Phages can be found in environments such as soil, rivers, sewage, or even the human body. The most effective ones are selected and combined to create treatments for people suffering from specific infections. Phages can be used to treat infections where antibiotics don’t work and used in combination with antibiotics to make antibiotics work better. Phages are abundant in nature, genetically diverse, and, unlike antibiotics, do not disrupt the body’s natural microbiome.
How long have phages been used for?
We don’t have to reinvent the wheel when it comes to phage therapy, we can build on a century of phage therapy pioneered in places like Tbilisi, Georgia, where phages have long been used to treat infections. Today, with ready access to genome sequencing and advanced microbiology tools, we can take this legacy forward in a modern, evidence-based way. We can also use genetic engineering to enhance phage properties. For example, by altering the range of bacteria that they kill, or enabling them to deliver other drugs to bacteria.
What is the status of UK phage use today?
There is a complex scientific and historical backdrop that has caused complexities with all aspects of developing phages as medicines. Despite their promise, clinical applications remain limited due to barriers in scientific understanding, regulation, and manufacturing. This information was beautifully collated and articulated in a recent UK Government Inquiry in the House of Commons. We address all of these obstacles head-on.
Our history: Establishing the Centre for Phage Research
Despite it being an unfashionable research area for decades, myself, and colleagues at the University of Leicester have been pioneering phage therapy for nearly 20 years. Studying phages requires specific approaches and equipment and, by developing new ways to find, study and sequence phages, we have laid the foundation to take their clinical development forward.
With the recent generous donation from Jimmy Mayer as a legacy to his late wife Becky Mayer, we have established the Becky Mayer Centre for Phage Research (BMCPR) and are now perfectly poised to use this resource to build on our vast experience to unlock new ways to combat bacterial infections. We have the pleasure of working in a multidisciplinary environment at the University of Leicester, where we are uniquely positioned in the UK to take phage research all the way from initial isolation through to clinical trials. Our work is further strengthened by close collaboration with the UK Health Security Agency (UKHSA), the Medical and Healthcare Products Regulatory Agency (MHRA), various NHS Trusts, and the Eliava Institute in Tbilisi, Georgia, which has decades of experience treating thousands of patients with phages.
Current activities: The Becky Mayer legacy in action
Thanks to the transformative resource, we have embarked on a two-year mission to expand our phage infrastructure and research capacity and to take specific phage products closer to being used in humans. We are currently creating a state-of-the-art phage bank, without which further phage development would not be possible. Medium term, our goal is to do the mechanistic, modelling, and machine learning work needed to ensure the very best phages are selected for therapy. Our long-term goal is to work with doctors to tackle AMR.
From July 2025 to June 2027, we will focus on four key pillars of activity.
Expanding our phage biobank (collection)
We will tackle the major bottleneck of scientific understanding of phages, to ensure the most relevant phages are developed for therapy. To do this, the world’s most comprehensive accessible library or ‘bank’ of phages suitable for clinical development will be created by formalising and dramatically expanding our existing phage collection. All phages will be characterised according to their biological and genomic data – how they work and what their DNA looks like – and machine learning will be used to link these two aspects.
Surprisingly, 70% of all known phages have been isolated on 20 bacterial genera – a very small subset of diseases. We at the BMCPR will work on more types of important disease-causing bacteria, despite them being difficult to work with. Our already 3,000-strong phage collection is being fully characterised and joined by 10,000 new phages and up to 3,000 bacterial strains for testing purposes. Each phage will be preserved, sequenced, and screened for therapeutic potential.
Using advanced imaging to establish how phages infect bacteria, and using host-range and potency studies, we will identify the most effective phages for further development. To support this, research assistants are being hired and critical lab infrastructure, such as -80°C freezers, spectrophotometers, growth chambers, automated liquid handlers, and sequencing technologies, are being purchased. Excitingly, we now have a GridION DNA sequencer, which will enable the genomes of 1,000 phages or more a week to be unravelled. This will allow the best phages to be selected and developed like never before.
Mining the phage bank for medical innovation
Having sequenced our phages, we will mine their treasure trove of genetic information – much of which is novel and uncharacterised – to identify promising antimicrobials. We will capitalise both whole phages and on products that they encode, for example endolysins, that allow them to burst bacterial cell walls, killing them as they are released from the cell. Using advanced computational methods and machine learning, the genomic signatures that govern phage effectiveness will be decoded. By leveraging the Medical Research Centre CLIMB computing infrastructure, we will turn genomic data into actionable medical insights. Our bioinformatics team is complemented by protein biochemists and structural biologists to identify and produce new phage-encoded compounds that could serve as new medicines.
Producing phages at scale
Effective phage therapy requires reliable production, and to expediate this we will use our phage biology knowledge to identify parameters for scale up. We have already shown that phage yields can be increased a thousandfold using Cellmaker® technology. Now, we’re scaling up by purchasing additional Cellmaker® units and cutting-edge purification, concentration, and fill-finish equipment to make pharmaceutical-like products. This phase will ensure that, once we identify therapeutic phages, we can produce them to clinical-grade standards and thus be able to transfer this technology to units who can make the phages at the appropriate production standards.
Testing phages in pre-clinical models
Promising phages must be tested in real-world conditions before being used in humans. Our pre-clinical research facility uses mouse models to assess safety, efficacy, pharmacokinetics, and immune response. This data is essential for regulatory approval and clinical trials. With additional staff and resources, we will generate the rigorous evidence needed to take phage therapy from lab to clinic. Remarkably, we can see that just one dose of phages can remove Klebsiella bacteria from a mouse bladder. This motivates further work to refine existing experiments and develop new ones for other diseases.
Martha Clokie, Professor of Microbiology, Becky Mayer Centre for Phage Research
Cross disciplinary work within the BMCPR
Phage work crosses discipline boundaries and we have been fortunate to have very talented and open-minded graduate students within our BMCPR team, funded by the University of Leicester, College of Life Sciences, the Institute of Precision Health, the National Institute of Health and Care Research (NIHR), as well as from the Medical and Biotechnology and Biological Research Councils and Wellcome.
Directing our work with the Phage Compass
We have a strong collaborative relationship with the Phage Compass, which we co-lead with researchers from the Globe Institute at the University of Copenhagen in Denmark, centred around advancing the computational tools essential for modern phage therapy. Together, we have developed cutting-edge platforms to rapidly characterise phages, predict host ranges (which bacteria that phages kill), and assess phage-antibiotic synergy. This partnership has allowed us to integrate advanced machine learning algorithms and AI-driven modelling into phage selection processes, significantly accelerating the identification of therapeutic candidates. By combining BMCPR’s deep expertise in phage biology with Phage Compass’ pioneering computational frameworks, we are setting a new standard for precision phage therapy – one where phage choice is scientifically optimised for clinical success.
The JPIAMR Consortium Project: Let’s do the translational pieces together
The BMCPR is proud to lead a major new international research consortium funded through the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). This ambitious four-year project brings together leading research groups from the UK, Sweden, Germany, France, Poland and Australia to tackle one of the complex parts of phage translation. Phage collections across countries will be assembled and compared, creating a shared biobank of well-characterised phages. These phages will be systematically tested against multidrug-resistant E. coli and Klebsiella pneumoniae – two of the most urgent AMR threats – using harmonised laboratory protocols developed at the BMCPR. We will explore how these phages work in combination with key antibiotics used for urinary tract and respiratory infections, and uncover optimal combinations.
The project will also assess the likelihood of phage resistance developing, optimise formulations for stable and effective delivery, and investigate the body’s immune response to phages to ensure that therapies are both safe and long-lasting. Cutting-edge models, including dynamic laboratory-based platforms and animal models, will allow us to test how phage-antibiotic combinations behave in real-world scenarios and support the design of future clinical trials.
Phages for global health: Expanding access to life-saving therapies
For nearly a decade, we have also worked closely with Phages for Global Health (PGH) – an international non-profit organisation dedicated to equipping scientists and public health leaders in low- and middle-income countries (LMICs) with the knowledge and tools needed to combat antimicrobial resistance using phage-based solutions. Through training programmes, technology transfer, and capacity-building initiatives, PGH is helping to establish local phage research and therapeutic development in regions where AMR has the most devastating impact. We have developed the scientific training for Phages for Global Health training workshops, ensuring that researchers in Africa and Asia can isolate, characterise, and apply their own phages to locally relevant problematic bacteria, empowering communities to build sustainable, locally-driven solutions for infectious disease treatment and prevention.
The future with long-term investment: A national and global phage powerhouse
The Becky Mayer Centre will lay the foundation for a push to tackle drug-resistant infections and chronic diseases through phage therapy. It will play an essential role in national progress and the UK to a growing global movement to realise the full potential of phages in modern medicine.
We will translate our vision for the future of healthcare by curating and capitalising on the world’s most comprehensive phage bank, developing regulatory-grade production protocols, and working with partners to deliver tested, targeted therapies. In doing so, we hope to transform what was once a niche scientific interest into a cornerstone of 21st century medicine. We will build on the groundwork and information learned from our current animal trial and animal data, to target specific phage sets for the most urgent pathogens. AI-driven solutions and a patient-first ethos will help to establish platforms to apply robust pipelines to multiple bacterial pathogens.
With continued investment, the Centre will make the UK a global hub for phage therapy, saving lives, reducing healthcare costs, and offering hope where antibiotics have failed. As AMR continues to rise, so too does the urgency and the promise of phage science. Building on growing enthusiasm from practising clinicians, we are actively establishing collaborative partnerships that will be critical for ensuring phage therapy moves swiftly and safely from the lab to the clinic, where it has the potential to transform how we care for patients facing drug-resistant infections.
Please note, this article will also appear in the 22nd edition of our quarterly publication.
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