88 A novel approach to the development of a murine model of cystic fibrosis associated chronic pulmonary bacterial infection

Research into the immunopathogensis of chronic bacterial colonisation of cystic fibrosis (CF) patients has been hampered by lack of a suitable animal model. Whilst models of chronic infection have been described, they rely on the use of artificial embedding material to prevent rapid clearance of the bacteria. We hypothesised that careful selection of the bacterial isolate, mouse strain and infection regime, will result in a clinically relevant murine model of chronic S. aureus (SA) and P. aeruginosa (PA) infection without the need for embedding materials. Previously published models have largely used PA01 and lab attenuated SA strains. We have screened several hundred clinical isolates of SA and PA and selected 5 strains of each for murine infection experiments, based on genotype and phenotype. The selected SA isolates include haemolytic strains from CF and non-CF sputum. The PA isolates originated from CF or ICU patients and were selected based on phenotype including ability to form biofilm in vitro. Significant differences in the in vivo virulence of these strains have been shown. Equally essential is mouse strain. C57BL6 mice are used almost exclusively, however this strain are inherently resistant to bacterial infection. We have compared the survival and colonisation of C57BL6, A/J, BALBc, Biozzi, FVB/N, NIH, SJL, CD1, MF1 and NMRI female mice with PA and SA. Identifying a combination of mouse and bacterial strain resulting in the prolonged survival of the animal whilst maintaining chronic pulmonary infection, will allow investigation of the intricate immunological and physiological disease processes involved during chronic pulmonary infection of CF patients.