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If you’ve never heard of a phage before, you’re not alone. The word “Bacteriophage” (or “phage”, for short) comes from the words “bacteria” and the greek word “Phagein” meaning “to eat”. That’s exactly what they do to bacteria. Phages are the most abundant entities on our planet. In fact, if you stacked every living thing on top of each other to make one tower, and stacked every phage in a second tower, they would be approximately the same height. How tall would this tower be? It would extend to the moon and beyond. Unlike the viruses that cause the common cold or flu, phages only attack and kill bacteria and are not capable of recognising human cells.
Besides from being found everywhere, phages may hold the key to one of the biggest threats that modern healthcare faces. Antibiotic resistance. Alexander Fleming, credited with the discovery of antibiotics, was the first to mention the term resistance. Just as every life form grows and evolves to overcome the stresses of surviving on planet earth, so too do bacteria. As they are exposed to antibiotics more and more frequently, they are able to learn, adapt, and overcome. This has led to the birth of new kinds of diseases, often referred to as “superbugs”. Diseases that modern medicine cannot cure. In a high profile review from 2014, it was estimated that 10 million people worldwide could die every year as a direct result of antibiotic resistance. (Note: there are various complications when it comes to these calculations, so take this with a pinch of salt. Click here for more) in 2019, superbugs killed more people than malaria or HIV/AIDS.
So, how can phages fight these seemingly impossible odds?
If you’ve ever seen the Apollo 11 spacecraft landing on the moon, you already know what a phage looks like. The “legs” of the phage land on the bacterial cell, and recognise proteins on the surface. These proteins are very specific. A phage will often only attack one species of bacteria. Once a phage has landed, and has recognised its target, the next stage can begin. Just as Neil Armstrong emerged from the lunar lander, the phage also releases its own cargo. DNA. Drilling in to the bacterial surface, it injects DNA into the bacterial cell. The DNA provides instructions, a blueprint, of how to make more phages. Tricked by the foreign DNA, the bacteria becomes a phage factory. It builds more and more microscopic spacecraft until there is no more room inside the cell. As the pressure builds, the surface of the bacterial cell bursts, releasing hundreds more phages into the environment, ready to find more bacteria to eat.
Not only do phages have the astonishing ability to recognise superbugs, their ability to tell the difference between target and non-target bacteria means that they leave all of the good bacteria in our gut alone.
But it gets even cooler, and a lot more complicated. we can use phages to reverse superbugs back into their weaker form, so that they can be killed by antibiotics once again. Imagine a bacteria has infected a patient. The doctor will give them antibiotics. Some bacteria will die, but others may adapt to be immune to the antibiotic. They could do this by building a miniature pump, to remove the antibiotic and avoid harm. As the infection grows, eventually all of the bacteria learn how to pump the antibiotics out. As quicky as that, we now have a superbug on our hands.
Now imagine we find a phage with special legs that recognise bacteria with pumps. Suddenly, bacteria with pumps are killed. In response, the bacteria try to overcome this attack by destroying all of their pumps, in an effort not to be recognised by our phage. the bacteria are now vulnerable to the antibiotic once again.
The San Diego Rescue: A Bacteriophage success story.
This approach to treating superbugs has already been used. Dr Steffanie Strathdee found a bacteriophage for her gravely ill husband after a holiday to Egypt turned into a fight against superbugs. Surviving sepsis multiple times, and going into a coma, Dr Strathdee and a team of scientists brought her husband, Tom, back from the grip of this deadly disease after just 3 days of treatment where all antibiotics had failed. I had the pleasure if interviewing Dr Strathdee myself as part of a campaign to redesign the UK’s approach to “last resort” medicine.
Read the full story here
