For decades, antibiotics were able to reliably protect against harmful bacteria. But in the meantime we have to fight with bacteria that are resistant to antibiotics. Remedy could create the phage method from Eastern Europe. Now a large research started in Germany project.
Gone are the times in which Penicillin and other antibiotics as a miracle weapon were considered. Resistance to antibiotics and multi-resistant germs from spreading. Around 33,000 people per year in Europe, these Super-organisms such as multidrug-resistant Pseudomonas aeruginosa or Staphylococcus aureus to the victims, of which 2400 in Germany alone, and the trend is rising. These latest Figures announced by the EU epidemic authority ECDC in the journal Lancet.
Phage therapy in Eastern Europe, proven for a long time
Because bacteria have the ability to this resistance to other germs to pass on, the antibiotic therapy irrevocably to their limits. An Alternative is therefore urgently needed. But what was in some Western countries, such as Germany, is hardly known: It has been around for a long time a treatment, which destroys without antibiotics, or in addition to antibiotics, the bacteria quickly and safely – the so-called phage therapy, which is carried out for decades in the former Soviet Union very successfully.
In the Cold war, antibiotics were scarce, and so we took advantage of phage as a bacteria fighter. The Georgian Eliava Institute for phage therapy, developed into a center of research and delivered to his weddings with 1500 employees, the entire Soviet Union with drugs.
“Has begun the phage therapy 100 years ago, in principle, soon after their double discovery by Frederick Twort and Félix dHérèlle,” says Christine Rohde, curator of the working group of bacteriophages at the Leibniz-Institute DSMZ GmbH, Braunschweig, Germany. In Paris dHérèlle began to heal children in a still-existing children’s hospital with the phage. In individual cases, phage therapy in Western Europe is practiced today in France, and more and more in Belgium. Also elsewhere on the planet – for example, in the United States and Australia, there are research centres.
Phages are the natural enemies of bacteria are
But what phages are, exactly? The name comes from the Greek word phagein for devour and that is exactly what can these natural enemies of bacteria. “Bacteriophages from the nature of the regulation of the bacterial mass on the earth, in all the environments,” explains the expert in more detail. Phage are part of our Microbiome, are in and on our bodies, are to be found in the air, the water and the earth – wherever bacteria occur. Overall, two types can be distinguished:
1. So-called temp retirement bacteriophage, the genome of the bacterium, there is a biological role, and with your germ-in this respect closely connected. They can be mobilized under some conditions, but also from its genome and other bacteria transmitted, in this Moment, you resemble phages, the virulent.
2. Virulent or lytic (dissolving) bacteriophages, there will probably be for almost every germ matching phages, the pathogen, just like a typical Virus, it does kill. Only these phage are desired for application targets, not the first. Modern genomics can distinguish between the two phage types.
The phage therapy effect
In order for this second group, the lytic bacteriophage is, for the medicine to be most interesting. “Almost everywhere, where bacteria are undesirable, can help a suitable phage in a goal-oriented,” says Christine Rohde. “Lytic bacteriophages kill the right bacteria by Dissolving or Burst of the bacteria,” explains the mechanism of action.
Phage from nature can be systematically searched for and characterized, purified, and then used and may – well documentation-considered and with an accompanying intensive – first of all, in clinical trials, and a single catchment in the human cases, keep medical therapy, summarizes the expert, the phage therapy. It is, therefore, a tailor-made treatment, wherein it is always essential to find the appropriate phage for the specific germ.
Phages against bacteria – the devil with Beelzebub cast out?
Phage specific viruses of bacteria – phage therapy could therefore be for the people, also risky, or at least side effects to exercise, the fear, according to the Motto – the devil with Beelzebub cast out. “Phage have no toxic or other known side effects, not affect the liver not the kidneys, not to attack the stomach, influence our Microbiome, in addition to fighting bacteria,” says Christine Rohde.
Against phage, bacteria can be immune – but not dramatically
As soon as the bacteriophage of the germ is no longer available, so once you have done your job, they die and disintegrate. Resistance and multi-resistance, as in the case of antibiotics, the great and, above all, sustainable risk, the phage therapy, although bacteria against phage resistant or can be. However, without the problems of new phage isolate, the nature is in this aspect of quasi-inexhaustible. Or phage mixtures consisting of several phages can be used against a germ, If a Phage effect is insufficient, the next Phage.
Phage therapy is not a substitute for antibiotics
Targeted destruction of the germs without the risks of side effects and sustainable resistance – with these features could be phage to the therapy in bacterial infections and antibiotics replace. The scientist denies this: “It would be completely unrealistic, because it is precisely when rapid assistance is needed, such as in the case of a bacterial-induced pulmonary or bladder infection, the doctor prescribes an antibiotic.”
This is done first, often without knowing the seed carefully, or to have a antibiogram, because for the patient, valuable time would be lost. “For the phage therapy would, however, not identified until just the germ on the bacterial species level, the appropriate phage searched and, possibly, from a phage Bank prepared the infrastructure is missing (yet).”
Of the phage therapy are intended to benefit primarily the sick, which no antibiotic can help, Severely. This is the case in Sepsis, severe wound infection or advanced diabetic ulcer – dramatic diseases, the mountains there is often a high risk of Amputation or even death. There are, however, for phage therapy, virtually no limit to the “application form” and also all of the significant bacterial pathogens through phage attack.
From the phage to the drug study Phage4Cure
All the therapeutically used phage must be well characterized. “We need to know for each individual phage, all of his on the genome-encoded abilities and bioinformatics and be able to assess the table. The is today possible, it was 10 years ago, more complicated and much more expensive,“ says the researcher.
This is currently being implemented at the Leibniz-Institute DSMZ GmbH, Braunschweig,. The phage Bank of the DSMZ is the largest in Germany and one of the few in Europe. It contains a significantly growing number of phage that could be used therapeutically.
In a September 2017 study commenced, Phage4Cure, is currently researching the Suitability of phages for therapy purposes in a targeted manner and tested, because phages are not approved for use in Germany and the EU (yet) as a medicinal product and the phage therapy is not yet carried out long ago by default.
Phage4Cure consists of four project shares in the following four consortium partners:
1. The search for phage, your comprehensive biological characterization and selection for the additional project interests, the object of the DSMZ.
2. These results and the phage will go to the Fraunhofer Institute for toxicology and Experimental medicine ITEM. The phage purified and as a medicinal product prepared in a, i.e., pharmacologically reproduced and toxicity, as well as to all the necessary regulatory requirements are checked.
3. The pre-clinical part of the study, with ultimately healthy subjects, the phage get to the security to confirm.
4. The clinical administration, here be Ill with of the in Germany new treatment in a targeted manner and according to precise conditions of a clinical study treated.
Part 3 and 4 will be carried out by the Charité Research organization, as well as the Medical clinic with focus infectiology and pneumology at the Charité.
The pharmaceutical industry shows little interest
The project is funded with just under four million euros to 100 percent by the Federal Ministry of education and research (BMBF). The pharmaceutical industry is not involved. However, an emerging interest from the industry generally, probably smaller Pharma companies to take this new path.
Phage4Cure runs for three years. Until the results are analyzed, it will take some time. It is important to emphasize that Phage4Cure is the project of a specific clinical study and not width phage therapy is initiate in the Routine.
However, with the Basis of successful clinical trials according to Western standards could phage therapy in Germany in the The future is a potent, well-tolerated Alternative or a complement to antibiotic therapy for critically-ill.