A longitudinal evaluation of localised chronic Pseudomonas aeruginosa infection in cystic fibrosis rat models

Abstract

Recurrent bacterial infections with Pseudomonas aeruginosa result in chronic airway inflammation, lung damage and eventual respiratory failure, and are the major cause of morbidity and mortality in people with cystic fibrosis (CF). Animal models are essential for understanding disease progression and assessing potential treatments in the presence of infection. Previously reported P. aeruginosa lung infection rodent models for CF research have some weakness, including acute infection rather than chronic, associated mortality, use of laboratory strains of P. aeruginosa and the use of non-CF rodents. The aim of this study was to create a localised P. aeruginosa infection in wildtype and two CF rat models, by delivering bacteria embedded agar beads using a miniature bronchoscope. The resulting infection was well tolerated by all animals of all genotypes with no mortality associated with the procedure or infection. Histologically the affected regions were localised to the right lung, with bronchopneumonia present. Bacteria persisted for 9 weeks (63 days) in all genotypes, with lung function changes observed by day 63 of the infection.