The enemy of my enemy is my friend
by Guest Author on 19 Nov 2019
PhD student Erin Attrill, of the Living Systems Institute at the University of Exeter, is the runner-up of our 2019 Max Perutz Science Writing Award. She explains how she’s aiming to harness the power of ‘viruses that infect bacteria’ to overcome antibacterial resistance.
The year is 2050, the stench of plague fills the air and 10 million people are dying from cuts and grazes due to an enemy that cannot be seen. You would be forgiven for believing that we had entered a dystopian, parallel future, but alas not. This is the current future of mankind if we do not address the ever-growing threat: antibiotic resistance.
Whether we want to face it or not, our antibiotics are failing. Drugs that we have relied upon to so effectively treat bacterial infections are no longer working due to these crafty bugs becoming resistant to them. Over time, bacteria have evolved to survive antibiotics, with this “survival of the fittest” process resulting in populations of menacing “superbugs”. No matter how many different antibiotics we throw at these resistant microbes, some can no longer be killed and so what were once minor infections become fatal.
So how can we fight back!?
One avenue is to discover and develop new antibiotics. However, this has proven to be extremely costly and difficult, so alternative options are being explored. Mankind’s possible saviour: bacteriophages.
Bacteriophages, or simply phages, are viruses that infect and kill bacteria. Just as humans get viruses like flu, bacteria suffer from their own invaders which hijack the bacterial cell and turn it into a virus making factory, before killing them. With their large bulbous head and spindly legs (think War of the Worlds alien invader fighting ships), they are perfectly adapted for attaching to bacteria. Phages are the optimal killing machines. Currently, phages are not widely used to treat infections in the Western world as not enough is known about them. If we want to be able to harness the power of these microscopic bacteria killers, then we need to know more about how they work.
Most research studying bacteria and phages use methods that involve growing billions of cells in a test tube, and looking at how fast the population grows and dies on average. But this is not always the most informative. Imagine you want to know how fast humans run 100m. Someone tells you the average time is 15 seconds. Although all humans, not everyone would take 15 seconds. Clearly if Usain Bolt ran the race he would be much quicker, and the man who decided to hop all the way much slower! This also applies to bacteria. Even though they should all be identical, individual bacteria can behave very differently.
My work lets us identify the Usain Bolts and the Hop-Alongs of the bacteria world, as well as many others in between. I want to know which responses occur when we expose bacteria to phages and how this may affect the killing ability of these viruses.
I use technology called ‘microfluidics’ that allows me to isolate and experiment on individual bacteria. With ‘micro’ meaning small, and ‘fluidics’ relating to the movement of liquids, I perform experiments on bacteria with equipment no larger than a postage stamp. Using networks of thousands of tiny channels, I can trap single bacteria in their own tiny chamber under a microscope and watch what happens when I add phages. Over the course of a day, I can continually monitor and photograph the same cells and record whether they are growing, dividing and even the exact point at which they lyse – that is, when they burst open releasing hundreds more phages.
I have observed that although all identical, some bacteria die instantly, but others grow much faster and divide multiple times before finally lysing hours later. Perhaps most importantly, some bacteria in the experiments are not killed by the phages at all. These bacteria survive the exposure and fill their chambers with more bacteria offspring. What makes these cells special and able to survive is unclear, and one aim of my work is to use microfluidics to try and understand why.
It is important to understand these differences to be able to optimise how many phages would be needed to eradicate the bacteria in a human as a potential treatment. If most bacteria are killed with two hours of phage treatment, a person may begin to look healthy, but if the “Usain Bolt” variants survive, then they could cause the infection to return. A longer dose or a higher concentration of phages may be required to eradicate the entire population so we need to fully understand how the different cells behave.
There is no need to be afraid of the word ‘virus’ – the good news is that phages cannot infect human cells. These minuscule invaders are the enemy of bacteria and so we should harness their power to defeat our bacterial foes. As stated, the enemy of my enemy is my friend. So let’s welcome in the age of the phage.
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