Fighting Bacteria with Viruses: Szeged Researchers Join a Major Phage-Therapy Programme

At the heart of the problem is the growing global threat of antimicrobial resistance, particularly bacterial resistance to antibiotics. As some antibiotics gradually become less effective, conditions including chronic wounds, recurrent urinary tract infections and infections around implanted prosthetic devices are becoming increasingly difficult to treat.

Three projects addressing a global threat

Recognising the urgency of the situation, the European Commission is providing more than €45 million in funding for three large-scale phage-therapy research projects under the Horizon Europe programme. Phage therapy uses viruses known as bacteriophages, which selectively destroy particular bacteria. Each consortium has received around €15 million to conduct multinational clinical trials assessing the safety and efficacy of the treatment.

One of the three projects is REPhRAME, coordinated by Frankfurt University Hospital (Universitätsmedizin Frankfurt). It combines phage therapy with restoration of the gut microbiome to tackle recurrent urinary tract infections caused by multidrug-resistant strains of Escherichia coli (E. coli). Researchers from HUN-REN BRC are members of the consortium.

P-PEAKS UTI is investigating personalised phage therapy in women with recurrent E. coli infections, with a particular focus on breaking down the protective biofilms formed by the bacteria. The third project, PHAGE4DAIR, aims to complement the surgical treatment of early prosthetic-joint infections caused by Staphylococcus aureus with phage therapy.

All three projects share the same goal: to generate the clinical evidence required to bring phage therapy closer to regulated and more widespread medical use.

A two-step approach targeting the source of infection

The approach adopted by REPhRAME, in which HUN-REN BRC is participating, is particularly innovative. Rather than addressing only the immediate symptoms of persistent urinary tract infections, it also targets a possible source of recurrence.

Recurrent infections are often caused by E. coli strains that survive courses of antibiotics by persisting in the gut, before recolonising the urinary tract. Repeated antibiotic treatment can, however, contribute to the spread of resistant bacteria and disrupt the healthy balance of the gut microbiome.

The REPhRAME consortium therefore plans to use a two-stage therapeutic strategy:

• Targeted phage cocktail: The first stage involves the use of CRISPR-enhanced phages against the coli strains responsible for the infection. The researchers aim to select phages that specifically target the pathogenic bacteria while causing as little disruption as possible to the rest of the gut microbiome.
• Microbiome restoration: This will be followed by a treatment known as INTESTIFIX001, developed by the Cologne Microbiota Bank. The treatment uses gut bacteria from healthy donors to help restore the natural balance of the intestinal microbiome, reducing the likelihood of pathogens becoming established again and the infection recurring.

The clinical feasibility of the therapy is being evaluated in a randomised, placebo-controlled Phase Ib/IIa trial conducted in several countries. The study is assessing both the safety and efficacy of the treatment and comparing three strategies: phage therapy alone; phage therapy combined with antibiotics; and phage therapy followed by microbiome restoration.

The trial is examining not only whether phage therapy can reduce the use of antibiotics, but also which patient groups, treatment sequences and microbiological conditions are associated with the best outcomes. In addition to clinical data, the researchers are collecting microbiological, immunological and microbiome data. This will allow them to gain a more detailed understanding of how the treatment works and of the factors that influence its success.

Hungarian researchers provide a ‘compass’ for phage therapy

Although the basic principle of phage therapy can be expressed simply — viruses destroy bacteria — putting it into practice requires exceptional precision. Phages are highly specific, attacking only certain bacterial strains. This gives them an advantage over broad-spectrum antibiotics, but it also presents a challenge.

Successful treatment depends on carefully mapping the properties of individual phages. Researchers must understand which phages interact with which bacteria, and how these relationships may change during treatment.

This is the task being undertaken by the Laboratory of Translational Microbiology at HUN-REN BRC, led by Bálint Kintses. Using data-driven approaches and computational modelling, the team is investigating how to understand and predict which bacterial strains a particular phage can target effectively.

Their work could help move phage therapy beyond isolated experimental applications and turn it into a treatment strategy that can be planned, measured and interpreted in a clinical setting.

‘One of the greatest promises of phage therapy is its specificity: with the right selection, it can be directed against the bacterial strains causing the infection without broadly destroying other bacterial communities. But to achieve this, we need a precise understanding of the relationship between phages and bacteria. What is particularly exciting about the REPhRAME project is that this knowledge can be applied within a major European clinical trial,’ said Bálint Kintses.

From basic research to the patient’s bedside

The project illustrates how a fundamental research question — understanding the relationship between phages and bacteria — can become the basis of a large-scale medical intervention tested in humans, provided that sufficient international collaboration and resources are available.

Each of the sixteen partners, including universities and research institutes from Germany, the UK, Switzerland and Latvia, contributes a different area of expertise. The Szeged laboratory provides precisely the knowledge needed to move phage therapy beyond isolated applications.

The programme began in June 2026 and will run for five years. If the clinical trials confirm the safety and efficacy of the approach, it could in the longer term help reduce antibiotic use, lower the incidence of recurrent infections and establish phage therapy as part of European clinical practice.