Antibiotic resistance is a huge problem

To date, Professor Thomas M. Kessler has been tilting at windmills, a struggle that has often left him feeling miserable and helpless. He is the Senior Physician in Neuro-Urology at Balgrist University Hospital and a professor in the Faculty of Medicine at the University of Zurich. In his clinic, he sees patients every day who are suffering from painful, dangerous urinary tract infections. Until now, there has been virtually only one treatment: antibiotics. But antibiotic resistance is growing and the disadvantage of antibiotics is that they also kill the «good» bacteria in the gut flora. New therapies are urgently required.

«Antibiotic resistance is a huge problem throughout the world. We desperately need alternatives,» stresses Kessler. He has launched the interdisciplinary ImmunoPhage research project that is taking a fundamentally new approach to treating UTIs. The initial results are highly promising. They are based on a study that Kessler’s team took part in in Georgia. The ImmunoPhage project is the only one of its kind in the world.

Balgrist University Hospital traditionally treats patients who have developed complex neurological problems following an illness or accident. These include sufferers of Parkinson’s disease and multiple sclerosis, paraplegics, and stroke victims. Thomas M. Kessler and his team also treat people who are essentially healthy but who suffer from recurring UTIs and bladder infections that have a serious impact on their quality of life. «Apart from symptoms such as pain and the frequent need to pass urine, these infections can also be harmful to patients’ overall health if they spread to the kidneys. But the pathogens often do not respond to antibiotics,» explains Kessler. The physician suffers along with his patients: «This is a major motivation for me to investigate new types of treatment.»

Viruses that strengthen the immune system

He is concentrating on bacteriophages as an alternative to antibiotics and these are the central focus of the ImmunoPhage project. Bacteriophages are viruses that infect bacteria and reprogram them with their genetic material. The bacteriophages then multiply and destroy more and more bacteria. In the ImmunoPhage project, these bacteria-killers or bacteria-eaters are being used to combat UTIs. In the future, this method could also help in the treatment of other chronic conditions such as lung and middle ear infections.

Professor Thomas M. Kessler from Balgrist University Hospital is working closely with the research team led by Professor Martin J. Loessner from ETH Zurich and the group headed by Professor Onur Boyman from the University of Zurich. Loessner and his team are among the world’s leading specialists in bacteriophages. The molecular biologists and geneticists are responsible for the engineering activities. They isolate the naturally occurring bacteriophages and propagate them. In the laboratory, genetic information is added to these «designer» bacteriophages, which are then used to attack specific bacteria that cause infections in the urinary tract. 

Soon available for the treatment of patients

«The network of specialists from different disciplines is essential to the project,» explains Professor Loessner from ETH Zurich. «We are the experts in bacteriophages, but we also need scientists who specialize in the immune system.» This is why the research group headed by Professor Onur Boyman is on board. He is the Director of the Department of Immunology at University Hospital Zurich and a professor in the Faculty of Medicine at the University of Zurich. Under the leadership of his team, chemical messengers are added to the bacteriophages which will stimulate the immune system. The aim of strengthening the immune system in this way is to enable it to fight off new infections in the future. Speaking about the project, Boyman says: «We are experts in the body’s defense system. I find it fascinating to work with colleagues who specialize in totally different areas.»

If everything goes to plan, the first designer bacteriophages could be used in clinical trials in Switzerland sometime in the next two years. The plan is to administer the bacteria-killers directly into patients’ bladders in liquid form via a catheter. The initiator of the ImmunoPhage project Thomas M. Kessler is confident about its prospects: «I hope that in five to ten years we will have an effective alternative to antibiotics.»

Bladder infection?
Clinic at Balgrist University Hospital
Diagnosis and treatment at University Hospital Zurich

Bladder infection (UTI, cystitis):
The urinary tract and urine itself normally contain no bacteria. When bacteria are present in the urinary tract and trigger an inflammatory reaction there and this causes problems for the person affected, it is described as a urinary tract infection (UTI). For anatomical reasons, small children and women are most likely to suffer from UTIs. Among men, the risk increases with age.

Bacteriophages:
Viruses that infect bacteria and reprogram them with their genetic material. The viruses then reproduce and destroy the bacteria.

Immunophages:
Bacteriophages are enriched in the laboratory with messenger substances that support the body’s immune response. In other words, the specific antimicrobial activity is combined with immunomodulatory properties.

Neuro-urology:
This discipline covers diseases of the lower urinary tract and the sexual organs after damage has been caused to the nerves that supply them.

Immunology:
This is the study of the biological and biochemical principles of the body’s defense against pathogens, such as bacteria, viruses and fungi, and other foreign substances.

Text and audio: Rebekka Haefeli
Pictures: Frank Brüderli
University of Zurich: Onur Boyman, Hendrik Koliwer-Brandl
Balgrist University Hospital: Thomas M. Kessler, Shawna McCallin, Lorenz Leitner, Sonja Milek, Swenja Lassen, Vera Neumeier
University Hospital Zurich: Onur Boyman, Jonas Van Belleghem, Lukas Heeb
ETH Zurich: Martin J. Loessner, Matthew Dunne, Samuel Kilcher, Jochen Klumpp, Aleksandra Svorjova, Susanne Meile, Jiemin Du
Hochschulmedizin Zürich: Corina Schütt