Dr Eleanor Mishra

“We all have many microbes on our skin and in our bodies, that’s our normal microbiome. Occasionally, this can tip into infection and when you have a catheter in your body there’s a weak point, a route of infection.

“We’re trying to understand which microbes survive on these catheters and work out how to do something about that,” explains Professor Mark Webber, Group Leader in antimicrobial resistance at the Quadram Institute.

Lung catheters reduce breathlessness in patients

Tens of thousands of people in the UK suffer from pleural effusions, a breathlessness caused by build-up of fluid in the lungs.

The ‘pleura’ is the space between your lungs and chest wall. “It doesn’t usually have very much fluid in it, but in various conditions you can get a lot of fluid in there, like heart failure or cancer,” Mark says.

One of the clinical solutions to pleural effusions is an indwelling pleural catheter. The catheter is a long-term drain which stays in the pleural space and patients can drain the fluid off at home, increasing independence and reducing hospital visits.

“It’s a really effective way of relieving breathlessness, but in 1 in 20 patients, the catheter gets infected,” reveals Professor Eleanor Mishra, a respiratory consultant at the Norfolk and Norwich University Hospital and an associate clinical professor at the University of East Anglia.

The bacteria causing these infections can grow in biofilms, formed of complex materials deposited by bacteria themselves, allowing them to evade our immune systems and antibiotics.

“It’s a really difficult problem to deal with because even when we treat people with long courses of antibiotics, we don’t seem to be able to sterilise and get rid of the bacteria from the catheters,” says Eleanor.

Different microbes colonise or infect pleural catheters

Mark and Eleanor received funding for a Clinical Seedcorn project to study these catheter infections and the microbes causing them. The project was jointly funded by the Quadram Institute and Norfolk & Norwich Hospitals Charity.

They collected infected and non-infected catheters from patients across the UK, in Norwich, Oxford, Cardiff and Glasgow.

Dr Dheeraj Sethi, academic clinical fellow in Respiratory Medicine at the hospital, then isolated the microbes on the catheters, which were sequenced by Mark’s group.

“We found that the longer these drains are in patients, the more likely they are to have bacteria on. We also found that a lot of the drains that weren’t infected still had bacteria on,” explains Eleanor.

Catheters with bacteria growing on them that aren’t infected are called ‘colonised’. Clinicians aren’t usually aware of these bacteria because patients don’t present with infection symptoms.

“Different bacteria cause colonisation and infection in catheters. Colonised drains tended have coagulase-negative Staphylococci bacteria whereas the infected drains much more commonly had Staphylococcus aureus,” continues Eleanor.

“So, if you find a catheter that’s been colonised by S. aureus then that almost certainly means it will cause infection and you might want to do something about this, like replace the catheter earlier on,” adds Mark.

Working towards targeted treatments for pleural infections

Mark and Eleanor have developed a unique library of bacteria that cause infection and colonisation on the pleural catheters.

“We plan to do further experiments on these bacteria, looking at growing them in a model of pleural infection to see what genes they use to adapt to life in pleural fluid and cause infection,” explains Eleanor

“We can test which antibiotics, or other treatments, are actually effective at preventing microbes from sticking to catheters, to try and give clinicians better tools to treat these infections if they do happen,” adds Mark.

Mark and Eleanor have a unique resource to target these infections – the drain in the infected fluid. “We’d be able to deliver targeted therapies directly to where the bacteria are,” Eleanor says.

Finding microbiological solutions to clinical problems through collaboration

Eleanor faces the clinical problem, the patients with infected pleural catheters, while Mark’s microbiology team is interested in understanding which microbes cause which problems to different types of people.

It was Dr Dheeraj Sethi who brought the two together. “I was approached by Dheeraj, who had done his Masters, as part of a medical degree, with Mark and his group. They’d been looking at neonates in the intensive care unit, studying resistance genes in sepsis-causing bacteria, a project that started from Clinical Seedcorn funding” remembers Eleanor.

Using the excellent sequencing facilities at the Quadram Institute, they whole genome sequenced the catheter bacteria to identify them and study their genetic differences.

“We use the same skills and abilities from our core day jobs in these clinical projects. We spend a lot of time understanding how microbes survive in the food chain, studying the biology of microbes and their genomes, which translates very easily in the clinical environment,” explains Mark.

From this research, they’ve also been working with Professor Sheng Qi and Dr Danielle Cox- Pridmore from the University of East Anglia to alter the 3D silicone surface of the catheters to prevent biofilm formation.

“It started off as quite a simple idea but it really developed into something novel and interesting,” Eleanor reflects.