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Niamh E. Harrington​, Freya Allen​, Ramón Garcia Maset and Freya Harrison

The opportunistic pathogen Pseudomonas aeruginosa forms biofilm infections in the lungs of people with the genetic condition cystic fibrosis (CF) that can persist for decades. There are numerous P. aeruginosa lifestyle changes associated with chronic biofilm infection that are cued by the CF lung environment. These include a loss of virulence, metabolic changes and increased antimicrobial tolerance. We have investigated P. aeruginosa PA14 biofilm infection over 7 days in an ex vivo pig lung (EVPL) model for CF, previously shown to facilitate formation of a clinically relevant P. aeruginosa biofilm structure with expression of key genes comparable to human infection. We have compared P. aeruginosa gene expression between sequential time points: 24 h, 48 h and 7 days post-infection, and investigated tolerance to polymyxins. Our results demonstrate that the EVPL model can maintain a P. aeruginosa biofilm population, which exhibits increased antibiotic tolerance, for at least 7 days. Differential expression of antimicrobial resistance-associated genes was not observed; however, there was significant upregulation of sulphur metabolism and maintenance of a structured biofilm. Our findings demonstrate that 7 days is a viable time point for studying established, chronic biofilm infection in the EVPL model and provide insight into the accompanying gene expression changes.