Viruses ‘eat’ antibiotic-resistant bacteria

Noemi Gomez | Noemi G. Gomez

Madrid (EFE) – Bacteria resistant to antibiotics are increasing worldwide and finding new drugs is becoming more difficult, making diseases such as tuberculosis or pneumonia difficult (sometimes impossible) to treat. Science is looking for alternatives, and one of the most promising is phage therapy.

Still experimental, but there are success stories in hospitals around the world, such as that of a woman infected with “Klebsiella pneumoniae” during the 2016 Brussels airport attack, a treatment that uses viruses called bacteriophages ., specialized in bacterial infections.

According to researchers Iñaki Comas (from Valencian Institute of Biomedicine) and Pilar Domingo-Calap (Institute of Integrative Systems Biology), they are able to fight the most complex bacterial infections, especially when used in combination with antibiotics. Biology) was summarized for EFE.I2SysBio, CSIC-Universitat de València.

The problem of overuse of antibiotics

Antibiotics represent one of the most revolutionary discoveries. According to a monograph in its “Science for Public Policy” collection, the Higher Council for Scientific Research (CSIC) said they laid the foundations of modern medicine, enabling not only cures for previously deadly infections, but also transformative interventions such as transplants. .

Unfortunately, he added, its overuse led to a dramatic increase in the resistance of bacteria — which mutated.

The World Health Organization says it is one of the greatest threats to global health, food security and development today, and its growth has reached dangerous levels.

The researchers developed a complex of three molecules that includes the antibacterial agent ciprofloxacin, which can increase the efficacy of existing antibiotics.
Detail of vials with laboratory samples. EFE/Jeffrey Agdas/Documents

Antibiotic-resistant infections kill 1.2 million people a year, a figure that could increase tenfold by 2050, according to a study by The Lancet that analyzed 204 countries. Urgent action is required.

“Finding a really new antibiotic is getting harder and harder, which is why we have to look for alternatives, one of the most interesting being phage therapy,” said Inar Iñaki Comas said. CSIC Global Health Platform.

Bacteriophages, a century old

Phages were discovered more than a century ago by French-Canadian microbiologist Félix d’Herelle, who first administered the therapy to patients in 1919.

However, the discovery of penicillin in 1928 and its subsequent commercialization and the boom in antibiotics superseded research on phage therapy, except for some countries in the former Soviet Union, such as Georgia, which today refers, despite its ups and downs, through his George Eliava Institute in Tbilisi (Eliava collaborated with d’Herelle and was executed in 1937).

But over the years, mainly due to misuse (years of overuse of antibiotics without prescription and agronomy), resistance started to emerge, leading to longer hospital stays, increased mortality and costs; for example, in Europe it costs about 200 euros to treat a normal case of tuberculosis , but if the “Mycobacterium tuberculosis” bacteria are multi-drug resistant, it will cost 30,000 euros.

In extreme cases, when it is extremely resistant, the cost could increase by up to 200,000 euros, Comas recalls.

It is this multi-drug resistance and super-resistance that has drawn attention and brought the scientific focus back to bacteriophages, for which antimicrobials on the market do not work.

Phage dynamics

Phages are viruses that infect and kill bacteria, and they are very abundant and very specific viruses in nature, explains Pilar Domingo-Calap of the Institute for Integrative Systems Biology (I2SysBio, CSIC-Universitat de València).

They identify and use specific bacteria; they use this cellular machinery to create new viruses and engage in an “arms race” with the bacteria until they can destroy it.

As such, they eliminate only the pathogenic bacteria that cause the disease, an ability that makes the therapy a good candidate for personalized precision medicine.

Researchers analyze samples. EFE/file
Researchers analyze samples in the laboratory. EFE/file

But this specificity can also be a disadvantage because you have to find the right mix of phage for each type of infection, and since it’s a virus, unlike drugs with a chemical structure, its pharmacodynamics are nearly impossible Forecast and measure.

Every patient’s outcome is different, which is why the way clinical trials are conducted and how results are interpreted must change. “We’re moving towards a very personalized medicine,” added Domingo-Calap, who attended the CSIC Cicero conference with Comas to talk about their research on superbugs.

they start to be produced in spain

Although work has been done at European level, proper regulation is lacking. Now phages are only used as sympathetic therapy and there are many success stories, some of them also in Spanish hospitals (phages are imported from USA and Belgium).

Production of these products has already started in Spain; Domingo-Carape’s laboratory has successfully isolated, characterized and developed them as therapeutic tools.

In fact, the researcher created Evolving Therapeutics SL in April, a “spin-off company” based in the Science Park of the University of Valencia, with the aim of producing biotech solutions based on these viruses, which are already in the initial stages Tested for about 10 years. There are very few patients.

One of the most famous cases of these viral treatments, published in Nature Communications, was that of a 30-year-old female victim of the 2016 Brussels airport attack who had received antibiotics for a bacterial infection associated with a bone fracture. Been out for almost two years.

After intervention and stabilization in the operating room, the victim developed septic shock from an infection in the left thigh surgical wound despite antibiotic treatment. The team at the Erasmus Hospital in Brussels then treated “K. pneumoniae” in combination with antibiotics.

This leads to clinical and microbiological improvement of the wound and its general condition.

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