Phage therapy is based on the use of viruses capable of infecting and destroying bacteria: bacteriophages, or phages (from “eating” in Greek). Harmless to humans, these viruses exist naturally in soils, lake waters and sewers, or even in our digestive tract. Unlike antibiotics, they have a very specific action: a given phage only attacks a limited number of bacterial strains. Enough to hope to destroy the targeted microbes without affecting the good bacteria of the digestive tract.
In practice, “we isolate the bacteria responsible for the infection, we select the phages effective against these bacteria and we administer them to the infected area”, specifies Dr Alain Dublanchet, who has treated some of his patients in this way. .
Phagotherapy: how to know if it works?
These bacteria “killer” viruses could constitute a solution in order to fight against pathogens resistant to antibiotics. And to remove the obstacles to their use (it is still unclear how many doses would be needed per day, at what rate, for what duration, and via what mode of administration phage therapy is the most effective), researchers from Inserm and of the Institut Pasteur have developed a model which makes it possible to better predict the effectiveness of phage therapy. The results of their research are published in the review Cell Reports.
Their new mathematical model helps to better define the interactions between bacteriophages and the pathogenic bacterium Escherichia coli in animals and to identify the key parameters which determine the efficacy of phage therapy. Several data from experiments in vitro and live (particularly information collected during experiments carried out using a model of lung infection in mice) were used to build this model.
“Some of the animals had been infected with a strain ofSchooli bioluminescent (to better follow it in the body). Among them, some had been treated with bacteriophages, according to different doses and routes of administration. The quantities of bacteria and bacteriophages thus measured over time made it possible to feed the mathematical model and to test which were the most important parameters for obtaining effective phage therapy” underline the two main researchers, in a press release.
This model could be used to predict the effectiveness of any bacteriophage against the bacterium it targets, to promote the clinical development of this new form of treatment.
Phagotherapy: who can benefit from it?
Phages were discovered in 1917 by the French-Canadian biologist Félix d’Hérelle. In 1919, this researcher managed to cure some dysentery patients with these viruses. Phage therapy had its heyday in the 1920s and 1930s. But after the arrival of antibiotics in 1940, it gradually fell into disuse. It did not begin to come back to the fore until the 1990s, after the problem of resistant bacteria was observed. In recent years, some doctors have used it successfully in several patients treated “on the sly”. Result: in 2016, the National Agency for the Safety of Medicines and Health Products decided to authorize access to this treatment under certain conditions.
The ANSM can thus grant a temporary authorization for use (ATU) if no treatment is effective and the vital prognosis of the person is involved or his functional prognosis is threatened – for example, if there is a risk of amputation. It remains a last chance treatment. This ATU is only possible if the infection involves one of the two bacteria for which there are phage solutions manufactured under good sanitary conditions: E. coli (responsible for urinary tract infections and burns) and Pseudomonas aeruginosa ( respiratory infections, surgical wounds and burns…).
>> The testimony of Caroline Lemaire, 46 years old: after a bad fall, I contracted an antibiotic-resistant staph infection in my right ankle. An ordeal of more than ten years then began, during which the complications were linked. The doctors ended up offering me amputation. Fortunately, I met Dr Alain Dublanchet and Pr Olivier Patey, who practiced phage therapy. I didn’t know what it was but I didn’t hesitate: it was the last chance treatment. After a few weeks, my wound improved. And since then, no relapse.
What are the possible developments?
In theory, phages could be used to treat almost all infections of bacterial origin: urinary, genital, gastrointestinal, respiratory, etc. “Only infections that involve bacteria entering cells, such as tuberculosis or Lyme disease, cannot be processed by phages. Because these viruses are unable to enter cells,” explains Dr Jérôme Larché, president of the association Phagespoirs. But phages could make it possible to treat several tens of thousands of French victims of infection not responding to antibiotics. “Improving access to phage therapy for these patients is both an ethical and a medical issue,” insists Dr. Larché.
>> A common practice in Eastern countries: if in France and in the West in general, phage therapy was gradually abandoned after the arrival of antibiotics, in Eastern Europe, particularly in Georgia, Poland and Russia, it remained a common practice. Certain pulmonary, cutaneous and digestive bacterial infections are treated there with bacteriophages. In Tbilisi, Georgia, there is a medical center dedicated to this practice, located in the Georges Eliava Institute.
Sources:
- Combination of in vivo phage therapy data with in silico model highlights key parameters for treatment efficacyCell reports, May 2022
- Interview with Dr Alain Dublanchet, former head of the microbiology laboratory at the Villeneuve-Saint-Georges Hospital Center, specialist in phage therapy and Laurent Debarbieux, microbiologist at the Institut Pasteur (Paris), Top santé, November 2017
Read also:
- Towards the use of viruses to fight against resistant bacteria?
- Antibiotics: are we going to replace them with phages?
- Antibiotic resistance: understanding the viruses that help fight bacteria