Researchers from Switzerland have developed a rapid test and therapy for urinary tract infections based on bacteriophages. Clinical studies are to follow.
Zurich – There are probably only a few women who don’t know it: the feeling of having to go to the toilet all the time, but then only a little and with burning. In the worst case, cramp-like pain is added. Bladder infections are among the most common bacterial infections. Although they are usually unpleasant, they are rather harmless, at least in women, who are affected far more frequently than men.
Antibiotics are often prescribed for this, even if they are not always necessary. But the symptoms usually go away quickly – provided the remedy works against the triggering bacteria. Due to increasing resistance, however, this is no longer guaranteed. This problem is exacerbated by the fact that broad-spectrum antibiotics are often prescribed because it is not possible to quickly identify the “culprit”. A corresponding diagnosis would take days.
Bacteriophages as an alternative to antibiotics in urinary tract infections?
Researchers at the Swiss Federal Institute of Technology in Zurich (ETH) see bacteriophages as a possible alternative to antibiotics in urinary tract infections. In cooperation with the Balgrist University Hospital in Zurich, they have developed a rapid test on this basis – and also a therapeutic approach for which bacteriophages have been genetically modified in order to destroy the bacteria more efficiently.
Phages, for short, are highly specialized viruses that infect bacteria and destroy them – and only certain strains. They are therefore also called “bacteria eaters”. Phages and their effects have been known for more than 100 years, but the triumph of antibiotics pushed out attempts to use them against bacteria.
Only recently, the Office for Technology Assessment at the German Bundestag recommended intensifying research on phages and regulating them less rigidly than before. So far, no drug based on phages has been approved in the EU and Germany; they may currently only be used in exceptional cases, for example as an individual attempt at healing when other means are no longer effective.
Bacteriophages used against the main triggers of urinary tract infections
For the study, the Swiss team led by Martin Loessner from the ETH research group for food microbiology identified phages that target the three main triggers of urinary tract infections: Escherichia coli, Klebsiella and enterococci. The researchers then modified the natural phages in such a way that the infected bacteria produce a light signal after contact that can be easily measured.
With this method, it says in one Communication from the ETH, the “pathogenic bacteria could be detected directly and reliably in the urine sample” – and that within less than four hours. “In the future, the method could make it possible to prescribe a suitable antibiotic immediately after the diagnosis and thus prevent the development of resistance,” it continues.
Rapid test aims for more sensible use of antibiotics
However, the test not only aims at a more sensible use of antibiotics, but also at future treatment with phages. At the same time, it should enable a prediction of a “tailor-made” phage therapy. Because the strength of the light signal indicates how efficiently the phages used in the test act against the pathogens in the sample: “The more the sample lights up, the better the bacterium responds to the therapy.”
A major advantage of phages is that they only attack a single target bacterium. One disadvantage, however, is that “they are not interested in completely killing their host, i.e. the disease-causing bacterium,” explains Samuel Kilcher, one of the study authors.
Genetically modified phages are designed to kill bacteria
In order to increase the effectiveness, the researchers genetically modified the phages so that they also produce bacteriocins inside the bacteria they infect – proteins that kill bacteria. These should be particularly effective against those bacterial strains that have changed their surface in such a way that phages no longer recognize them (comparable to resistance to antibiotics). “This two-pronged attack makes the therapy more effective,” says the ETH statement.
The Swiss researchers emphasize that their work is a proof of concept that proves that an approach is fundamentally promising, i.e. not yet a clinical study. This should now represent the next step in which the team wants to test the phage therapy on selected patients. (Pamela Dörhöfer)