Abstract

Pseudomonas aeruginosa causes a range of opportunistic infections. In cystic fibrosis (CF) patients, chronic lung infections with P. aeruginosa are the main cause of patient morbidity and mortality. The Liverpool Epidemic Strain (LES) of P. aeruginosa is a particularly successful, aggressive transmissible strain, widespread in the UK, present in North America and associated with both greater patient morbidity and increased antibiotic resistance. Using genomic and phenotypic analysis, we have studied the LES in a variety of in vitro and in vivo models, as well as directly in samples from CF patients, in order to identify characteristics that may contribute to its success. Using signature-tagged mutagenesis we have identified novel prophages and genomic islands that contribute to the ability of the strain to establish infections. In addition, transcriptomic analysis enabled us to identify a novel quorum-sensing related phenotypic specific to the LES . We have also been studying LES population divergence directly in CF patient samples and in an artificial sputum medium biofilm model. These studies reveal extensive diversity in LES populations within individual patient sputum samples, leading to considerable variations in phenotypes, including antimicrobial resistance. We are using the biofilm model to better understand what drives the diversification.