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Bacterial infection in cystic fibrosis
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2008 – 2011 Postdoctoral Fellowship Response of populations of Pseudomonas aeruginosa to antimicrobial challenge during chronic infections in cystic fibrosisDr C Winstanley |
Dr Winstanley is a Senior Lecturer in the Division of Medical Microbiology at Liverpool University.
Cystic fibrosis (CF) is the most common life-threatening inherited disease in the UK. Most patient morbidity and ultimately mortality is due to chronic lung infections caused mainly by bacteria. The most common and important CF pathogen is Pseudomonas aeruginosa, which causes infections that, once established, are impossible to eradicate. During chronic pulmonary infection, CF patients suffer a decline in lung function associated with periodic exacerbations triggered by bacterial products.
Very little is understood about the responses of populations of P. aeruginosa to antimicrobial challenges during chronic lung infections in cystic fibrosis. The conventional approach is to investigate this in rats with chronic respiratory infections and in CF mouse ‘models’. However, this project will attempt to model population behaviour in artificial sputum media (ASM) and assess whether this in vitro model can be used to predict population responses to antimicrobial challenges in CF.
The DHT-funded project will support a study of P. aeruginosa population behaviour in CF patients, and test the usefulness of the ASM as an alternative to animal ‘models’ for studying the behaviour of bacterial populations.
The Research Group will monitor populations of the Liverpool Epidemic Strain (LES) of P. aeruginosa in a cohort of patients over a three year period. This will be done by carrying out a series of phenotypic and genotypic tests on multiple isolates from individual sputum samples during periods of exacerbation and during stable periods.
The new approach will be used to follow diversification from uniform starting populations and test antibiotic combinations in a way that cannot be achieved in real patients. A better understanding of bacterial population fluctuations in response to antibiotic challenges during chronic infections in CF will help clinicians to make better informed choices of antibiotic therapy.
Publication
Fothergill JL, Mowat E, Ledson MJ, Walshaw MJ & Winstanley C (2010). Fluctuations in phenotypes and genotypes within populations of Pseudomonas aeruginosa in the cystic fibrosis lung during pulmonary exacerbations. J Med Micro 59:472-481.