Viruses Help Fight Antibiotic-Resistant Bacteria

The World Health Organization (WHO) considers multi-resistant germs to be among the greatest threats to health. In the European Union alone, 33,000 people die each year as a result of bacterial infections that cannot be treated with antibiotics. Therefore, alternative treatments or medications are urgently needed.

Bacteriophages, the natural enemies of bacteria, are a promising solution. There are millions of different types of these viruses on earth, each of which specializes in certain bacteria. In nature, viruses use bacteria to reproduce; they insert their DNA into bacteria, where the viruses multiply rapidly. Ultimately, they kill the cell and go on to infect new cells. Bacteriophages work as a specific antibiotic by attacking and destroying a particular type of bacteria.

viruses for health

“Bacteriophages offer enormous potential for highly effective personalized therapy of infectious bacterial diseases,” he notes. Gil Westmeyer, Professor of Neurobiological Engineering at the Technical University of Munich (TUM) and Director of the Institute for Synthetic Biomedicine at Helmholtz Munich. “However, in the past, it was not possible to produce bacteriophages in a targeted, reproducible, safe and efficient manner, even though these are exactly the decisive criteria for the successful production of pharmaceuticals.”

Now the research team has developed a new controlled production method to create bacteriophages for therapeutic use. The basis of this technology was established by a students group at TUM and the Ludwig Maximilian University of Munich (LMU), who won a prize at the 2018 International Genetic Engineering Machine (iGEM) competition. This group later gave birth to the start-up Invitris, which is currently developing a platform technology for phage-based drugs.

The cornerstone of the new technology, which is already in the patent application process and is now being used in new research at TUM, is a special nutrient solution in which bacteriophages are formed and reproduced. The nutrient solution consists of an extract of E. coli and does not contain viable cells; this is a fundamental difference from previous methods of bacteriophage production, which traditionally used cell cultures with potentially infectious strains of bacteria.

In the TUM laboratories, the Munich team has now been able to demonstrate the targeted production of bacteriophages in the cell-free nutrient solution: the only necessary component is the genome, the simple DNA, of the desired viruses. The genome contains the complete blueprint for the formation of bacteriophages. When the DNA is injected into the nutrient solution containing the molecular components and enzymes of the E. coli bacteria, the proteins are assembled according to the blueprint: thousands of identical copies are generated in just a few seconds. “Not only is this production method fast and efficient, it’s also very clean: the process eliminates contamination by bacterial toxins or other bacteriophages, which are potential complications in cell cultures,” says Westmeyer.

Personalized antibiotics

But is the new cell-free nutrient solution really suitable for the production of bacteriophages that could be used in individual therapies? The researchers tested the idea together with the Bundeswehr Hospital Berlin: Using a bacterial sample from a patient suffering from an antibiotic-resistant skin infection, the Munich team evaluated a promising novel bacteriophage and isolated its DNA. The phage was then produced in the cell-free nutrient solution and finally used to successfully combat multidrug-resistant bacteria.

A genetic file for emergencies

“Our studies demonstrate the feasibility of a cell-free method to produce effective bacteriophages for personalized medicine that can also be used to treat multidrug-resistant germ infections,” says Westmeyer. She adds that in the future the methodology could ideally be used in conjunction with a genetic archive that would store the DNA of the relevant bacteriophages. Whenever necessary, this file could be used to rapidly produce whole bacteriophages in the nutrient solution, test their efficacy, and then apply the phages in the appropriate combinations, says Westmeyer, adding that while this work is still in the basic research stage However, the method has potential for clinical trials.