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Treating drug-resistant infections with viruses?


Genetically modified viruses can be used against antibiotic-resistant bacteria

A young girl has now successfully managed to treat a life-threatening and drug-resistant infection with Mycobacterium abscessus from genetically modified viruses.

In a recent study by the University of Pittsburgh, the researchers were able to fight a drug-resistant infection by using newly created viruses. The results of the study were published in the English-language journal "Nature Medicine".

Wound infection usually ends in death

A 15-year-old cystic fibrosis patient received a double lung transplant in September 2017. After a week, the resulting cut became light red. A drug-resistant infection (Mycobacterium abscessus) spread quickly, causing painful wounds and swollen nodules. It is very sad if a lung transplant patient has such a wound infection, which in children leads to an agonizing course of the disease, which usually ends in death, the study authors explain.

What are phages?

Since the usual standard treatments failed, Isabelle's mother asked for alternatives. The doctors became aware of so-called phages. Phages are viruses that can destroy bacteria. Researchers put together a cocktail from the first genetically modified phages ever used for treatment. It was a composition that was directed against a Mycobacterium, a genus that also includes tuberculosis (TB).

After six months of treatment, the condition improved

After six months of tailor-made phage infusions, Isabelle's wounds healed and her condition improved without serious side effects, the researchers report. This is a convincing so-called Proof of conceptThe authors add, even if it is only a case-by-case study and the result still has to be checked in a rigorous clinical examination.

Difference between antibiotic treatment and phage therapy

So-called phage therapy has been around for many years, but until recently it was relegated to marginal medicine in most countries, mainly due to the use of antibiotics. In contrast to broad-spectrum antibiotics, individual phages usually only kill a specific strain of bacteria. This means that treatment that works against one person's infection will fail in another person infected with a different variant of the bacterium. Phages can also be toxic. However, a number of recent successes against antibiotic-resistant bacteria have revived interest and prompted large US universities to set up phage research centers. Drug-resistant TB strains are a particularly attractive target for phage therapy.

Bacteria in the mucus of the lungs

M. abscessus and other bacteria often colonize the thick mucus that accumulates in the lungs of people with cystic fibrosis, a genetic disease that affects around 80,000 people worldwide. The infections can lead to severe lung damage, for which a transplant is the last resort. For example, Isabelle had lost two thirds of her lung function. However, the infection persisted after the transplant and continued to threaten her life.

Cocktail should prevent resistance from forming

In a collection of more than 15,000 phages, the researchers spent three months searching for phages that could kill M. abscessus, which were isolated from the patient's wounds and sputum. They actually found three possible candidates. The researchers wanted to combine the phages into a cocktail to reduce the likelihood of M. abscessus developing resistance, but there was a catch. Two of the three components are so-called moderate phages, which have repressor genes that limit their lethality. To make these two phages reliable bacterial killers, the researchers removed the repressor genes using a gene editing technique that the laboratory had developed for the study of phage genetics.

How was the course of treatment?

Isabelle received an infusion of the phage cocktail for the first time in June 2018. Her wounds began to dry within 72 hours. After six weeks of intravenous treatment every twelve hours, the infection was almost gone. However, traces of the disease remained, so she still receives infusions twice a day and the treatment was applied directly to her remaining lesions. It is now possible for the girl to lead a normal life as a teenager again, to go to school, to spend time with friends and to take driving lessons for a license. The researchers are optimistic that the infection can be completely eliminated over time.

Success promotes research in this area

Success has promoted research into phages, the researchers say. Other phages have already been examined, they infected and killed M. tuberculosis in tests in test tubes. The research team hopes that phages could prove to be useful weapons against drug-resistant bacterial strains at some point. (as)

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Video: How to use viruses to tackle drug-resistant infections (January 2022).