Adapted phages against antibiotic resistance – UMC Utrecht

Researchers from UMC Utrecht and TU Delft have received a grant of more than 500 thousand euros from NWO to develop broader-based bacteriophages. With the help of such modified phages, the researchers want to overcome bacterial defense barriers, which are an important mechanism in bacterial resistance to bacteriophages.

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Bacteriophages (‘phages’) are viruses that can kill bacteria and are considered a promising alternative for treating infections caused by antibiotic-resistant bacteria. They have a high specificity for their host bacteria and can often infect and kill only one individual strain of one specific bacterial species. This makes targeted antibacterial therapy possible, without side effects on the so-called ‘good’ bacteria. Researchers from TU Delft recently discovered that certain bacteria build up defense mechanisms to prevent them from being killed by phages. Certain strains of the bacteria Pseudomonas aeruginosa for example, have more than 100 different defense mechanisms and a single strain can have as many as 20 in its genome. Fortunately, phages have developed a variety of defense mechanisms against such bacterial strains. In this project, researchers want to combine these defense mechanisms and create a phage that can infect a broader range of bacterial strains with different defense mechanisms. This broadening of bacteriophage activity is seen as an important step in the clinical application of phage therapy.

Synergy in collaboration

The combined research team consists of medical microbiologist Dr. Pieter-Jan Haas (Department of Medical Microbiology, UMC Utrecht) and microbiologist Prof. Dr. Stan Brouns (Department of Bionanoscience, TU Delft). Pieter-Jan Haas is project leader and is responsible for coordination and communication between the academic researchers. Two postdocs (one in Utrecht and one in Delft) will work on the project for a period of 2 years. In addition, an analyst at the UMC Utrecht who specializes in phage techniques offers support in the production of phages, high throughput assays, sequencing and bacterial modifications. NWO has awarded an amount of €511,754 for the project.

The knowledge and techniques in the field of phage defense systems and phage biology of TU Delft in combination with the advanced reading systems, sensitivity tests and microbiological genome editing in a clinical setting of the UMC Utrecht creates a unique synergy. The combined skills and knowledge, the availability of clinically relevant P. aeruginosastrains at the UMC Utrecht and phages at TU Delft and the translation to clinical application make these partners the best candidates for this project.

Tackling antimicrobial resistance

According to the WHO, antimicrobial resistance (AMR) is a global threat to health and development and requires urgent action. The European Centers for Disease Control (ECDC) estimate that up to 35,000 people in Europe die every year from infections caused by bacteria resistant to antibiotics, a number that is likely to increase in the future. In addition to death and disability, these infections lead to longer hospital stays, the need for more expensive medications and higher healthcare costs. Without effective antibiotics or alternatives, the success of modern medicine in treating infections, including during major surgery and chemotherapy, would be compromised.

Study coordinator Pieter-Jan Haas explains: “Tackling current and emerging infectious diseases and AMR requires alternatives to the use of antibiotics, and phage therapy has potential in this area. Due to the increase in AMR and the limited supply of new antibiotics, interest in the use of antibacterial phages has increased again. Before bacteriophages can be applied on a large scale, we need more high-quality clinical studies that demonstrate the effectiveness of phages in the treatment of infections. The first well-controlled studies with phages for the treatment of infections are underway But a better understanding of the interaction between phages and bacteria and how bacteria evade phage infections is essential to select the best phage candidate for these clinical studies. We look forward to starting this project and developing a set of customized bacteriophages that have a broad spectrum of action against clinical P. aeruginosa-tribes. If successful, the efficacy and safety of these phages could be investigated in clinical trials, for example in patients with implant infections caused by P. aeruginosa.”

NACTAR program

The program Novel Antibacterial Compounds and Therapies Antagonizing Resistance (NACTAR) from NWO from 2017 focuses on research into new sources and alternatives to antibiotics. A total of almost 1.6 million euros has been made available together with the Ministry of Health, Welfare and Sport for the 2023 round. Four studies have been selected in which the effect of new antimicrobial agents and methods is validated. This can make an important contribution to the healing of bacterial infections against which current medications and antibiotics no longer work.