Fight against antibiotic-resistant bacteria: what alternative to new drugs based on bacteriophage viruses

There is no doubt that the bacteria have become resistant to antibiotics. And its consequences on human health, nor: an estimated 700,000 people die each year from antibiotic-resistant microorganisms.

As predicted by the World Health Organization (WHO), if nothing changes, by 2050 the figure will reach 10 million deaths per year.

And worse, new antibiotics are not being developed quickly enough. According to a recent WHO study, of the 43 antibiotics in development, none is a new drug that adequately targets a priority group of resistant bacteria. In fact, no new type of antibiotic has been marketed since the 1980s to fight the most troublesome bacteria, most of which belong to a group that microbiologists call gram-negative.

And so he warned in 1945, during his acceptance speech of the Nobel Prize for the discovery of penicillin, Dr. Alexander Fleming, who at that time showed that bacteria could become resistant to the drug if they were exposed to non-lethal amounts. “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations insufficient to kill them, and the same has occasionally happened in the body.”he explained.

His warning was premonitory, and today many bacteria are resistant to multiple antibiotics, and therefore difficult to treat in patients.

Guy-Charles Fanneau de la Horie is CEO of Pherecydes Pharma, a French biotechnology company, and on the current outlook he expressed his opinion: “The fruits most within reach have already been harvested. Now it is more complicated and difficult to discover new antibiotics ”.

An alternative to finding new drugs is to use spaceship-shaped viruses called bacteriophages (or phages) that feed on bacteria. When phages come into contact with bacteria, they inject DNA into them and replicate within them. Soon, virus accumulations erupt to infect more bacteria.

De la Horie’s company is focused on producing these phages and delivering them to patients infected with drug-resistant bacteria. Their phages kill three species of bacteria known to be resistant to first-line antibiotics: Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.. All three are responsible for many drug-resistant infections contracted in hospitals, where the most dangerous germs reside, De la Horie noted. The country.

Injecting phages into patients should be perfectly safe, as they do not attack human cells. And, unlike many antibiotics, which affect multiple species of bacteria, phages are more precise and do not kill “good” gut microbes. “They are very specific,” noted de la Horie. For example, a phage that kills S. aureus will have no effect on Pseudomonas ”.

Being a higher precision weapon, the right phage must be chosen carefully to kill the corresponding bacteria. For this reason, Pherecydes created labs to assess samples from sick people, analyze bacteria that cause problems, and choose a specific phage to kill them.

“We have discovered a small number of phages which we call ‘superphages’ because they are active against a whole series of strains within the same species”explained the specialist, who clarified that if a patient has Pseudomonas aeruginosa, a dangerous microbe that often attacks patients connected to a ventilator, he is given phages that kill more than 80% of the strains.

Although phage therapy has not yet been approved by the European Medicines Agency, Pherecydes has previously treated patients infected with drug-resistant bacteria after knee or hip surgery, using what is called ” compassionate use ”, when other treatment options have failed.

So far, the company has used phages to treat more than 26 patients, the majority in the main hospital in Lyon, France. And they would have treated three elderly patients with S. aureus infection in the knee replacement, as well as one patient with persistent Pseudomonas infection.

Researchers plan to start a trial on joint infections after hip or knee surgery later this year.

The company has also developed sophisticated phage production processes with the support of a project called PhagoProd. They are made in liters, but the plan is to go to tens of liters. A single milliliter in a vial can contain 10 billion phages.

And what could be better: When phages are injected into a patient or applied to infected tissue, they multiply inside the bacteria they target, increasing the amount of viruses ready to kill them.

The CEO of Pherecydes hopes that a large-scale trial with patients can begin in 2023. “We believe our products could be on the market no earlier than 2024, or maybe 2025,” he said declared.

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