Our body is the scene of the eternal struggle of trillions of bacteria and their adversaries, bacteriophages. Doctors want to harness these viruses as a much needed antibiotic supplement.
Berlin – Some people may find it risky to rub viruses into wounds, inhale them, swallow them, or even inject them into the bloodstream. But in the so-called phage therapy, viruses that feed on bacteria and are harmless to humans are actually used.
With the increasing number of antibiotic resistance, this form of therapy, which has been underutilized for a long time, is returning to receive more attention. But is it the solution to the great crisis in medicine? Two major German projects are about to treat patients.
Bacteriophages are constantly around and within us. An adult human is made up of about 30 trillion body cells, 40 trillion bacteria and 300 trillion phages, says phage therapy expert Christian Willy, director of the trauma surgery clinic at the Bundeswehr Hospital in Berlin. Bacteriophages are viruses that initiate multiplication programs in bacteria until the mass of newly produced viruses causes the bacterial cell to explode. Bacterial accumulations, for example in an inflammatory focus, can thus disappear quickly.
Milestone in sight
One of the projects in which patients will soon be treated is “Phage4Cure”, in which a therapy with inhalable phages against the dreaded hospital germ Pseudomonas aeruginosa is developed. The pathogen often colonizes the lungs of patients with cystic fibrosis. A phase I clinical trial on basic tolerability is expected to begin in late summer, says Christine Rohde of the Leibniz Institute DSMZ (German Collection of Microorganisms and Cell Culture GmbH) in Braunschweig. Contrary to what usually happens, there is also a direct cohort with patients. “If phase I is successful and patients feel better, then a real milestone for phage therapy in Germany will have been reached.”
In Germany, some patients are already being treated for whom the approved therapies available are ineffective. For example, by Christian Kühn, head of the National Phage Center at the Hannover Medical School. “I see what antibiotic resistance does every day,” the doctor points out. “We need alternatives”. More than 30 patients have already been treated in Hanover, often against it Staphylococcus aureusa bacterium that can cause stubborn wound infections.
The second major German project, the “PhagoFlow” project carried out by the Trauma Surgery Clinic at the Bundeswehr Hospital in Berlin, is also based on the individual production used for each individual patient – known as a masterful application. While “Phage4Cure” is about a clinical picture, a pathogen and an administered mixture, “PhagoFlow” is intended to treat different clinical pictures caused by different pathogens, as project manager Willy explains. From the second half of the year, the first patients could be cured, he hopes.
More known as penicillin
Bacteriophages have been used to fight infections for nearly a century. A good ten years were discovered before Scottish bacteria researcher Alexander Fleming discovered the antibiotic effects of penicillin in 1928.
One big difference between the two bacteria killers: While antibiotics work more like a weapon of mass destruction, phages are contract killers with a very specific target. They attack only one type of bacterium at a time, most often only one specific strain of a type, which makes their use complicated: first, it is necessary to find the appropriate phage for a patient’s respective bacterial strain. “And more than one strain usually plays a role in a critical infection,” says Holger Ziehr, head of pharmaceutical biotechnology at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM).
But where can you find suitable phages to fight a specific pathogen? Experts often choose a very simple source for this: “wastewater,” says phage researcher Alexander Harms of the Biozentrum of the University of Basel. First, the bacteria against which phages are to be used are grown on nutrient plates. The water sample arrives on the blight lawn. If there is a phage that kills the bacteria, a hole is created in the bacterial lawn: the virus is isolated from this point and multiplied in the laboratory.
substitute for antibiotics
So much more effort than pulling a pill that acts against many pathogens out of the drawer. But the miracle weapon of antibiotics risks becoming boring. It is estimated that over 30,000 deaths in the EU are caused by antibiotic-resistant bacteria each year. According to estimates, there are around 700,000 in the world. Ascending trend. Can phage therapy help?
In Eastern Bloc countries – where there was initially little access to antibiotics – phages continued to be used frequently. To this day, the institutions of such countries are world leaders, most notably the Georgi Eliava Institute in Tbilisi, Georgia. Other countries such as the United States, Belgium and France are now reviving this form of therapy. Examples from the US show that it is now possible to create a suitable phage therapy for a patient within 10 days, says Christian Kühn of the Hanover Phage Center.
Convincing results on phage efficiency in very large clinical trials, as they have become the required standard in drug research, are not yet available for phages which often can only be used individually, phage expert Christine Rohde says. Individual case reports and smaller studies show impressive success, German experts explain.
In a recently presented study, 20 patients with intractable bacterial infections were treated with bacteriophages. The therapy was successful in eleven patients, the researchers reported in the journal Clinical Infectious Diseases. As a result, there were no side effects. Ziehr refers to the heterogeneous group of participants, which included children and adults with various clinical pictures, complex infections and different types of pathogens. The fact that, given these circumstances, more than half of the participants responded to therapy is impressive, says the expert, who was not involved in the work.
Bacteriophages will not completely replace antibiotics, as experts point out. One promising way could be the combination of bacteriophages and antibiotics, based on the so-called phage-antibiotic synergy (PAS), explains Berlin phage researcher Willy. It has been shown that resistant bacteria can become sensitive to antibiotics again in a patient who has previously been treated with phages.