Understanding bacterial dominance in CF infections

Greta Šveikauskaitė, PhD student (Allsopp Group)

What is your current research in cystic fibrosis focused on?

Cystic Fibrosis is a genetic condition that affects many organs but has a particularly large impact on the lungs. CF causes the thickening of lung mucus, reduced clearance within the lungs and a frustrated immune system, creating a perfect environment for bacterial growth.

During infection, bacteria can lead to cell damage directly, but immune responses that do not effectively clear the bacteria can persist over time, resulting in damage that leads to reduced lung function.

Although the CF lung can be infected by a range of bacteria, Pseudomonas aeruginosa is the most common and most troubling. My project in the Allsopp Group focuses on how P. aeruginosa becomes dominant and outcompetes other bacteria.

“We do not fully understand how P. aeruginosa causes infection and becomes so successful. My work will hopefully reveal environmental triggers that lead to a boom in P. aeruginosa presence and make it more aggressive”

P. aeruginosa alters its behaviour in this environment and in response to other bacteria, and this is the focus of my PhD. One bacterial system I am particularly fascinated by is a protein nanomachine that it uses like a harpoon against other bacteria, or human cells, to inject toxins that lead to cell death. This system is called the type VI secretion system. I am researching how P. aeruginosa responds to the CF lung environment to arm itself for this bacterial warfare.

What impact do you hope your research will have for people living with CF?

I hope that findings from my research will help us better understand these bacteria. This is important as we do not fully understand how P. aeruginosa causes infection and becomes so successful. My work will hopefully reveal environmental triggers that lead to a boom in P. aeruginosa presence and make it more aggressive. Once we understand this, we could use these triggers as a guide for more effective future treatments.

What does a typical day look like for you as a PhD student?

My days are filled with experiment planning, literature reading, and a lot of experiments!

Collaboration plays a big role in CF research – how has this influenced your work?

I am part of the Precision CF Innovation Hub, part of the Translational Innovation Hub Network for CF Lung Health and Infection funded by LifeArc and the Cystic Fibrosis Trust.

This means that my work fits within the wider CF research landscape and I get to collaborate not only with researchers at Imperial, but also from other UK universities, and learn about broader CF research topics. I also interact and collaborate with clinicians, which helps remind me of the bigger picture beyond day-to-day laboratory work.

What are the next steps for your research?

I hope we are able to achieve better detection of the bacteria infecting CF lungs, coupled with increased understanding of their infection patterns, so we can deliver rapid and effective treatments that improve the lives of people with CF.

Looking ahead, what breakthrough would you most like to see?

I would love to see a way to restore natural innate immunity, with increased “good” (commensal) bacteria that could better equip the body with an active defence system against harmful bacteria such as P. aeruginosa.

Exploring polymicrobial infections in CF lungs

Shannon Blay, PhD student (Hughes Group)

What is your current research in cystic fibrosis focused on?

My research focuses on how the bacteria Pseudomonas aeruginosa (Pa) and the fungus Aspergillus fumigatus (Af) interact during co-infection in people with CF.

Lung infections in CF are common, and there is increasing understanding that these infections are polymicrobial—made up of many different pathogens. Pa and Af are the most common bacterial and fungal pathogens found in CF lungs.

Because people with CF have thicker mucus that is harder to clear, alongside an impaired immune response, infections often become chronic—triggering inflammation and progressive lung damage.

The introduction of CFTR modulators, such as Kaftrio, has been a huge breakthrough. However, these treatments are not effective for around 10% of people with CF, and even in those receiving modulators, chronic infections often persist and are difficult to treat due to antimicrobial resistance.

Research has shown that Pa and Af co-infection worsens patient outcomes, including requiring more frequent hospitalisation. It is therefore crucial to understand how these pathogens interact and why this negatively impacts health outcomes, with the aim of discovering new treatment targets.

My research explores how Pa and Af interact directly and indirectly, and how this affects their growth and survival.

What impact do you hope your research will have?

CFTR modulators, specialised healthcare and newborn screening have transformed outcomes for many people with CF. However, an ageing CF population brings new challenges, including chronic lung infections.

By researching polymicrobial interactions, I hope to contribute to a better understanding of how pathogens behave during infection so that we can treat them more effectively and alleviate symptoms. The opportunity to have a positive impact on people living with CF is what motivates me.

What does a typical day look like for you as a PhD student?

A typical day begins with checking my plan and writing a very ambitious to-do list. My experiments are time-dependent, so I usually carry them out in the morning.

After lunch, I focus on admin tasks, reading scientific papers and analysing data. Keeping accurate records is crucial, so I maintain both a lab book and electronic notes. I also regularly meet with my supervisory team or lab group—so my days can get very busy!

How has collaboration influenced your work?

“The collaborative nature of CF research is incredibly inspiring as an early-career researcher.”

Collaboration is central to my research, particularly as my project forms part of Precision-CF, one of four UK translational innovation hubs funded by LifeArc and the Cystic Fibrosis Trust.

I work closely with researchers within my group, including Dr Lillie Purser, to develop laboratory models of polymicrobial infection. We also collaborate with Professor Darius Armstrong-James to access A. fumigatus isolates from CF patients.

Our group is also exploring collaborations across departments, including with bioengineering. The collaborative nature of CF research is incredibly inspiring as an early-career researcher.

What are the next steps for your research?

My next steps are to continue optimising co-culture models to study polymicrobial interactions. I will then investigate how Pa and Af interact in different media, including synthetic cystic fibrosis medium, which mimics CF sputum.

This will help better simulate the CF lung environment and improve the clinical relevance of my research.

What breakthrough would you most like to see?

I would most like to see further advances in CFTR modulators or genetic therapies so that they can benefit everyone with CF, including those currently not eligible due to rare mutations or treatment intolerance.

Find out more about our Respiratory Infections research at NHLI and show your support by wearing yellow on the brightest fundraising day of the year, Friday 12 June.