Pseudomonas aeruginosa infection in cystic fibrosis: pathophysiological mechanisms and therapeutic approaches

ABSTRACT

Pseudomonas aeruginosa is a remarkably versatile environmental bacterium with an extraordinary capacity to infect the cystic fibrosis (CF) lung. Infection with P. aeruginosa occurs early, and although eradication can be achieved following early detection, chronic infection occurs in over 60% of adults with CF. Chronic infection is associated with accelerated disease progression and increased mortality. Extensive research has revealed complex mechanisms by which P. aeruginosa adapts to and persists within the CF airway. Yet knowledge gaps remain, and prevention and treatment strategies are limited by the lack of sensitive detection methods and by a narrow armoury of antibiotics. Further developments in this field are urgently needed in order to improve morbidity and mortality in people with CF. Here, we summarize current knowledge of pathophysiological mechanisms underlying P. aeruginosa infection in CF. Established treatments are discussed, and an overview is offered of novel detection methods and therapeutic strategies in development.

KEYWORDS:

• Pseudomonas aeruginosa
• airway
• cystic fibrosis
• sputum
• biofilm
• persistence
• antibiotic

Acknowledgments

All authors listed are members of, or affiliated with, the UK Cystic Fibrosis Trust Strategic Research Centre for Pseudomonas, which is funded by the Cystic Fibrosis Trust, UK.

Declaration of interests

The Strategic Research Centre for Pseudomonas is funded by the Cystic Fibrosis Trust, UK. JC Davies has been principal investigator on a number of trials for Vertex, PTC, Pharmaxis, Novartis and Forest. She has also served on Advisory Boards for several of these companies and has undertaken educational activities for their staff. All fees/ honoraria have been paid to Imperial College or the Royal Brompton Hospital. J Brundy receives funding from the Wellcome Trust, in addition to the SRC. SN Faust receives support from the National Institute for Health Research funding via the Southampton NIHR Wellcome Trust Clinical Research Facility and the Southampton NIHR Respiratory Biomedical Research Unit. P Freemont research is funded by the UK Engineering and Physical Sciences Council, Medical Research Council and Cancer Research UK. S Morales is an employee of AmpliPhi Australia, the Australian subsidiary of AmpliPhi Biosciences Corporation, a public US company developing Bacteriophage therapy. S Schelenz has received an educational grant from Astellas. J Webb receives funding from the Biotechnology and Biological Sciences Research Council (BB/L016877/1), National Institute for Health Research, Wellcome Trust (via Seeding Drug Discovery Award to Antabio Pharmaceuticals, France), and Public Health England. Z Takats’ research group receives grant funding from Waters Corporation both in the form of research instrumentation provided by the company and direct financial contribution to the research projects. The funded program focuses on the development of novel mass spectrometric techniques. Z Takats also acts as a paid consultant for Waters Corporation. The consultancy work focuses on the development of ambient ionization mass spectrometric methods. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by the Cystic Fibrosis Trust, UK.