Bacteriophages: learning more about these microbial puppet masters in cystic fibrosis

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The Royal Society’s Summer Science Exhibition takes place this week (6-10 July) and features an exciting exhibit on a specific type of virus called bacteriophages – a hot topic in cystic fibrosis. Trust-funded researcher Dr Jo Fothergill will be part of the team presenting, so amid her last-minute preparations, we caught up with Jo to learn more.

Dr Joanne Fothergill
Dr Jo Fothergill

What are bacteriophages?

Bacteriophages are viruses that infect bacteria, not people. You may also have heard them called phage for short. The name phage comes from the word “phagein” which means “to eat”, as phages were first thought to eat bacteria. They are absolutely tiny and can’t be seen without really powerful microscopes. They are a lot smaller than bacteria. There are a huge number of them on Earth, approximately 1 trillion for every grain of sand.

What do they do?

Phage can broadly do two things when they infect a bacterial cell. Some types can hijack the bacteria, turning it into a phage-making factory eventually causing the bacteria to split apart and die releasing newly made phages. These are called virulent or lytic phages.

Other types of phage can partner up with the bacteria becoming part of its DNA allowing it to gain more genes and changing the bacteria’s characteristics. These are called temperate or lysogenic phages.

A famous example of phage changing the characteristics of bacteria is the phage infection of Streptococcus pyogenes. Without phage infection it causes ‘strep throat’ (a painful throat infection), however after phage infection with a temperate phage the same bacteria causes the more serious infection Scarlet Fever. In this way, phage act as puppet masters, controlling how the bacteria behave.

How many different bacteriophages are there?

Phage are the most abundant biological entity on the planet. There are approximately 1031 phage, that’s too many to even think about saying the number! You get new phage all the time. The challenge really is to understand what they do and what genes they carry.

Why are you studying them in CF?

We are studying them in two ways. The first way is to understand whether and how temperate phage help bacteria cause CF infections. The other way is to understand how we can use lytic phages as a therapy.

In a project funded by the Biology and Biotechnology Research Council (BBSRC), we are studying how phage contribute to the biology of the CF lung infection causing bacteria Pseudomonas aeruginosa (P. aeruginosa). There are lots of slightly different versions of P. aeruginosa called strains. One particularly problematic strain for people with CF is the transmissible ‘Liverpool Epidemic Strain’(LES).

When the DNA of the LES strain was analysed, one of the major differences between this strain and other strains of P. aeruginosa was that there were quite a lot of sets of DNA from phages alongside the bacteria’s own DNA. We think that the phage help the bacteria cause infection but there is a lot that isn’t known about how they work. In particular, how they change what P. aeruginosa does.

At the University of Liverpool we are studying how we can use lytic phage as a therapy against bacteria that are resistant to all antibiotics. We have got some really exciting results testing them in the lab, but there is still a lot to learn about this area. Hopefully we can tell you more about this soon.

Could bacteriophages be used as a treatment for infections?

Yes. Researchers have known about phage and thought about their potential as a treatment for a long, long time (over 100 years!). However, they are a bit more challenging to develop than normal antibiotics.

There have been some really promising case studies including one from the US earlier this year where a patient had a really good outcome following phage treatment for Non-tuberculous Mycobacteria (NTM). However, we still have a lot to learn. We need to know what kind of self-defence bacteria might put up against phages (which could mean that a treatment wouldn’t work or wouldn’t work as well). We also need to understand more about what DNA the phages carry and how well they work in specific parts of the body such as the lungs.

It is unlikely that phages would replace antibiotics but maybe, in the future, some could be developed to the point of using them as part or in combination with other elements from an arsenal of weapons against multidrug resistant bacteria that are really hard to treat. There are lots of different approaches to combat antimicrobial resistance, and this could be one of them. However, for now, there are still some hurdles to jump though.

Tell us about your exhibition

The exhibition should be a lot of fun. The main activity is a virtual reality experience of how phage can act in the lungs of a person with CF. You can travel down the airways and encounter bacteria embedded in mucus and learn more about the different types of phage and how infection can result in death or giving superpowers to the bacteria.

We’ve also got some fantastic giant 3D models to show how specific phage are, and how they need to bind to a special receptor on the bacterial cell so they can work. Visitors will be asked to find the right combination of phage and bacteria and see what happens!

There’s also a chance to understand more about how computers can be used to overcome the challenges of finding out what the function of phage genes might be.

We’ll be at the Royal Society Summer Exhibition in London from the Wednesday 6 July until Sunday 10 July-10th. Come and visit!

If people can’t visit the exhibition, where can they find out more?

Please visit our website where you can find out more. 

You can also find us on Twitter and through the University of Salford and University of Liverpool  webpages. The team who put together the exhibition are Dr Chloe James @drchloejames , Dr Heather Allison @Hallison67, Dr Jo Fothergill @jojofoth , Dr Ian Goodhead @IanGoodhead , Dr Revathy Krishnamurthi @Revathykri and Dr Enrique González-Tortuero @EnriqueTortuero

Cystic fibrosis (CF) is a genetic condition which causes sticky mucus to build up in the lungs and digestive system. It affects more than 10,800 people in the UK. One in 25 of us carries the faulty gene that causes it, usually without knowing.

Your donations help us fund ground-breaking research, make sure that everyone has access to life-saving medicines and high-quality clinical care, and reach those with CF and their families that are most in need. Donate today to help everyone with CF live a life unlimited.

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