"Unlocking the Power of Phages: The Fight Against Antibiotic Resistance"

2023-05-19 05:30:00

The microbiome plays an important role in our health. Billions of microorganisms in the body influence almost everything in the body – from digestion to the immune system to our mood. But there are other, rather strange structures that settle in with us: bacteriophages – or phages for short. These are microscopic viruses that are even smaller than our gut microbes. These viruses infect bacteria and turn them into factories that make even more phages.

It has been known for over a hundred years that they exist – and a small group of scientists quickly recognized their potential. Because these viruses can kill bacteria, they should be used to treat a wide range of malignant bacterial infections. But that’s not how it happened.

Only a few decades after their discovery, phages as a therapy were largely abandoned in favor of antibiotics. But that is slowly changing now. As antibiotics fail and the deadly threat of antimicrobial resistance increases, interest in phage medicine increases. However, before we can use them adequately, we still have a lot to learn. In addition, people are afraid of viruses: who would want to swallow a drug consisting of infectious particles?

A disgusting factor in phages

“There’s a disgust factor,” says Chloe James, a microbiologist who studies phages at the University of Salford in the UK. However, these are different from viruses that infect us, such as B. Influenza, Ebola or COVID-19 viruses. Instead, phages specifically infect bacteria.

Both biologys have evolved side by side – wherever there are bacteria, there are phages to infect them. In fact, you can find them almost everywhere you look. “Phages are incredibly diverse and the most abundant organism on our planet, so they’re literally everywhere,” says James.

Many phages work by “pouncing” on the bacterium and injecting their own DNA inside. There the DNA can replicate. Eventually, the bacterium itself ruptures, releasing a blast of phages. However, not all phages work in this way. Some also insert their genes into the DNA of bacteria. This can stop the bacteria from multiplying — or even give them other powers, like the ability to cause an even more deadly disease or be resistant to the effects of antibiotics.

All of this is complex. On the one hand because there are so many phages, on the other hand because they all seem to be incredibly specific. For example, they only infect certain strains of bacteria. But if you find the right phage for the right bacillus, the potential for phage therapy is enormous.

phages from the compost bin

Several citizen science projects are therefore underway to encourage people to study the phages in their environment, whether they are lurking in the garden soil or in the compost bin. Most phages cataloged in biobanks come from wastewater. Some of these have already proven extremely useful.

In 2010, Lilli Holst, a student at the University of KwaZulu-Natal in South Africa, attended one Participated in a project to encourage students to find phages. She decided to look in her parents’ compost bin, among other places. Then, in a swab taken from the underside of a rotting eggplant, she found phages that were entirely new to science. She called her “Muddy”.

It turned out that this type of phage was able to kill a type of bacteria that can cause particularly unpleasant diseases. When, nearly a decade later, a teenager in London contracted an aggressive, multidrug-resistant infection after a double lung transplant, doctors gave her a maybe 1 percent chance of survival.

In a last-ditch effort to save her life, doctors injected her with the Muddy phages along with two other genetically engineered phages. She recovered within days and was able to leave the hospital a few months later. As featured in Tom Ireland’s forthcoming book “The Good Virus” on the subject of phages, Muddy was used on more than a dozen people in the years that followed.

30 active clinical trials of phage therapy

It is not easy to find the right phage for the task at hand. Therefore, scientists are working on alternatives. For example, phages could be equipped with the genes they need to infect specific bacteria that they want to kill. It may also be easier to use the chemicals that the phages make themselves, rather than the phage’s own production. They make enzymes that can poke holes in the walls of bacterial cells, causing them to burst. We could also treat people with these specific enzymes, says James.

In any case, the time seems ripe to bring phages back into the limelight. Antimicrobial resistance is on the rise; they are already responsible for millions of deaths a year. In the United Kingdom, the government is therefore examining whether phage research should receive more state money. Over 30 active clinical trials of phage therapy are listed in a US-maintained registry. Ireland’s pro-tech book is out this summer.

Once the research moves forward, there’s another challenge to overcome: the idea of deliberately introducing viruses into the body doesn’t appeal to most people.

That being said, Bacteria have benefited from some great PR over the past few years. Most people are now aware of the benefits of a healthy gut microbiome. Many people even swallow the corresponding active ingredients, starting with probiotic yoghurt. Could viruses also convince us? “We need to stop being so afraid of phages – and see what they can do for us,” says microbiologist James.

On the subject of phages, also listen to “Weekly”, the news podcast from MIT Technology Review: