In December 1945, during his Talk about accepting the Nobel Prize for the discovery of penicillin, Doctor Alexander Fleming He warned that bacteria could become resistant to the drug if exposed to non-lethal amounts. “It is not difficult to produce penicillin-resistant microbes in the laboratory by exposure to concentrations that are insufficient to kill them, and the same thing has sometimes happened in the body,” the scientist explained.
His warning was a premonition. Many today Bacteria are resistant to multiple antibioticsand subsequently difficult to treat in patients. This is because when antibiotics are used, bacteria create ways to eliminate, sabotage or circumvent the effects of the drug.
Implications for human health they are serious. An estimated 700,000 people die each year from antibiotic-resistant microorganisms. The World Health Organization (WHO) predicts that if nothing changes, by 2050 this number reaches 10 million deaths per year.
To make matters worse, we are not developing new antibiotics fast enough. According to recent WHO reviewOf the 43 antibiotics under development, there is no new drug that adequately targets the priority group of resistant bacteria. In fact, no new type of antibiotic has been marketed since the 1980s to deal with the most difficult bacteria, most of which are in a group that microbiologists call gram-negative.
The WHO predicts that if nothing changes, the annual number of victims will reach 10 million by 2050
“The fruits that are most within reach have already been harvested.” Discovering new antibiotics is now more complicated and difficult, ”says Guy-Charles Fanneau de la Horie, CEO of the French biotechnology company Pherecydes Pharma.
An alternative to the search for new drugs is the use of spacecraft viruses called bacteriophages (or phages) that feed on bacteria. When phages come into contact with bacteria, they inject DNA into them and replicate in them. Accumulations of viruses soon erupt and infect more bacteria.
De la Horie, Pherecydes, focuses on the production of these phages and their administration to patients infected with drug-resistant bacteria. Their phages kill three types of bacteria that are known to be resistant to first-line antibiotics: Golden staphylococci” Escherichia coli and Pseudomonas aeruginosa. All three are responsible for many of the drug-resistant infections that have occurred in hospitals that house the most dangerous microbes, notes De la Horie.
Injection of phages into patients should be completely safe, as they do not attack human cells. And unlike many antibiotics, which affect more types of bacteria, phages are more accurate and do not kill “good” intestinal microbes. “They are very specific,” notes De la Horie. “Like a phage that kills S. aureus will have no effect on Pseudomonas.
Because it is a weapon with higher accuracy, the correct phage must be carefully selected to kill the relevant bacteria. For this reason, Pherecydes has set up laboratories to evaluate patient samples, analyze the bacteria that cause problems, and select a specific phage to kill them.
“We have discovered a small number of phages, which we call ‘superphages’, because they are active against a number of strains of the same species,” explains the specialist. If a sick person has Pseudomonas aeruginosa, Dangerous microbes, which often attack patients associated with the ventilator, are administered phages that destroy more than 80% of the strains.
Phage therapy has not yet been approved by the European Medicines Agency, but Pherecydes has treated patients infected with drug-resistant bacteria after knee or hip surgery using so-called “compassionate use” if treatment has failed by other options. These infections are particularly difficult to treat with antibiotics. The problem is not minor. “It infects between 2% and 5% of hip or knee replacements,” says De la Horie.
To date, the company has used phages to treat more than 26 patients, mostly at a main hospital in Lyon, France. For example, reports show that he treated three elderly patients infection S. aureus in knee replacement, Yes Cas a patient with a persistent infection Pseudomonas. An attempt at joint infections after hip or knee surgery is scheduled for later this year.
Of the 43 antibiotics under development, there is no new drug that adequately targets the priority group of resistant bacteria.
The company has also developed sophisticated phage production processes with the support of a project called PhagoProd. They are produced in liters, but the plan is to increase them to tens of liters. One milliliter in a vial can contain 10 billion phages.
What’s even better: when phages are injected into a patient or applied to infected tissue, they multiply inside the bacteria they target, increasing the amount of virus ready to kill them. “Once the phages get into the presence of bacteria, it shouldn’t be necessary to apply more, because they multiply on their own,” explains De la Horie.
The CEO of Pherecydes hopes that in 2023 he can start an extensive study with patients. “We think our products could be on the market in 2024 at the earliest, or maybe in 2025,” he says.
It is better to prevent than to treat
One of the problem microbes Pseudomonas aeruginosa, is one of the goals of the project called BactiVax, which also deals with the problem of antibiotic – resistant infections. Instead of using phages or other methods to treat infections as they appear, BactiVax researchers are focused on vaccines.
The Pseudomonas they are a plague for patients in the intensive care unit, for patients with chronic obstructive pulmonary disease (COPD) and for patients with cystic fibrosis.
Bacteria can cause chronic and serious infections. “It’s quite common and sometimes it’s not really harmful,” says Irene Jurado, a doctoral student at University College Dublin, Ireland, “but it can be a problem for people with previous pathologies.”
If a child with cystic fibrosis becomes infected with certain strains when he is five or six years old, the microbe may remain in the lungs for the rest of his life, make it difficult for him to breathe and cause serious illness, the researcher adds.
Pseudomonas has a very long genome, which gives him great flexibility to adapt to various difficulties, which Jurado recently wrote. This gives you a special ability to develop antibiotic resistance. Thus, scientists have been working for decades without success to develop a vaccine against bacteria.
Jurado examines the proteins that the pathogen uses to attack lung cells. This could provide important components for the vaccine in the same way that our immune system instructs the SARS-CoV-2 spike from Covid-19 vaccines.
“We’re trying to find out what immune responses are needed to protect people from infection,” explains Siobhán McClean, an immunologist at University College Dublin, Ireland, who leads the BactiVax project. The proteins that bacteria use to attach to our cells are often a good target for vaccines. For example, the pertussis vaccine uses five different proteins that bind the bacteria to the cells that line the throat.
Unfortunately, bacteria are a tougher enemy than the covid-19 virus because it does not have one, but dozens of proteins on the outside. This means that what should be included in the vaccine is less obvious in the case Pseudomonas than in a pandemic virus targeting spicules.
However, researchers believe that the vaccine is worth the effort. “Our idea is that we can get a vaccine to prevent infection.” That’s better than constantly trying to treat (problem infections) with antibiotics, “says McClean. “We only have antibiotics of last resort, and when they run out, we’ll be in a dead end.”
this article It was originally published in English at Horizon, the EU’s research and innovation magazine. Research on this article has been funded by the EU.
Translation of NewsClips.