Strategic Research Centre: Personalised approach to Pseudomonas aeruginosa (PAPA)

Investigating better ways to detect ​Pseudomonas aeruginosa​, understanding how it settles in the lungs and developing more effective drugs for treating it.

Summary

Professor Jane Davies and her team of colleagues who are collaborating on this programme will investigate better ways to detect Pseudomonas aeruginosa, understand how it settles in the lungs on a strain-by-strain basis, and develop more effective drugs for treating it. The overall aim of the programme is to develop a personalised approach to treating Pseudomonas infection.

Background

Around two out of three adults with CF have persistent Pseudomonas chest infections leading to permanent lung damage and reduced lung function. Detecting Pseudomonas quicker is an important goal, as the sooner it is detected, the easier it is to treat. There are many factors that contribute to whether and how Pseudomonas becomes established in the lungs and how it can be treated. One of these is the fact that there are many different sub-species or ‘strains’ of Pseudomonas - which strain you’re growing in your lungs could make a difference to how it affects you and how to treat it. In particular, the strain of Pseudomonas present in your lungs makes a difference to how to break up its biofilm – a key element of antibiotic resistance.

Aims of the project

This Strategic Research Centre (SRC), led by Professor Jane Davies at Imperial College London, brings together a unique group of world-class scientists to deliver a research programme focussed on detecting, understanding and treating Pseudomonas infection. As such, the benefits of this research will be felt by the global CF community. The team will build on their existing work on Pseudomonas to apply cutting-edge new methods for detecting it, understand the differences in survival tactics between strains (and thus the variation in its effects on different people with CF) and develop biofilm-beating drugs that are tailored for each person with cystic fibrosis.

The three aims of the project are:

1. Improving early detection of Pseudomonas

The researchers will be looking at methods for rapid and easy detection of Pseudomonas. Three methods have been proposed for doing this: two are techniques for measuring Pseudomonas in breath and the third uses medical detection dogs. All of these areas of research are collaborative, working with colleagues from the industry, university and charity sectors respectively.

2. Exploring mechanisms of infection of Pseudomonas

An important key to understanding Pseudomonas infection in the lungs of people with CF is to understand how it reacts to its local environment. In this SRC, the researchers will be looking at what Pseudomonas does, and looking for chinks in its armour where drugs can cause a fatal blow. This includes looking at how it exists alongside other infections, how it switches on its own ‘survival instinct’ chemical reactions, and how our in-built methods of fighting infection could work with Pseudomonas.

3. Working towards an individualised approach to treatment

In the first SRC, researchers were focussing on developing drugs that could break up a barrier to antibiotics that Pseudomonas build known as a ‘biofilm’. For some strains of Pseudomonas the drugs seem to work well, breaking up or dispersing this barrier. However, in other strains of Pseudomonas, the same drugs seem to encourage more of a biofilm to form. The researchers would like to understand more about how people’s natural defence systems affect the formation of biofilms, and unravel what may be contributing to the strain-specific reactions to biofilm-breaking antibiotics.

Who is involved?

Lead Principal Investigator (PI): Professor Jane Davies (Imperial College London)

Co-PIs:

• Professor Anke-Hilse Maitland van der Zee, Amsterdam, The Netherlands
• Dr Paul Brinkman, Amsterdam, The Netherlands
• Dr Claire Guest, Medical Detection Dogs, UK
• Professor Zoltan Takats, Imperial College London
• Dr Huw Williams, Imperial College London
• Professor Jeremy Webb, University of Southampton
• Professor Alan Filloux, Imperial College London
• Professor Andrew Bush, Royal Brompton Hospital
• Dr Silke Schelenz, Royal Brompton Hospital
• Dr Darious Armstrong-James, Imperial College London
• Dr Amelia Shoemark, Royal Brompton Hospital
• Dr Andrew Jones, Royal Brompton Hospital
• Professor Eric Alton, Imperial College London
• Dr Gary Connett, Southampton Children’s Hospital
• Professor Saul Faust, University Hospital Southampton
• Dr Michael Kelso, University of Wollongong, Australia

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