title: A lung segmental model of chronic Pseudomonas infection in sheep.
abstract: BACKGROUND
  Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep.
  
  
  RESULTS
  Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>10(4) cfu/g).
  
  
  CONCLUSIONS
  The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom. david.collie@ed.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Collie
authors.forename: John
authors.initials: J
authors.lastname: Govan
authors.forename: Steven
authors.initials: S
authors.lastname: Wright
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Thornton
authors.forename: Peter
authors.initials: P
authors.lastname: Tennant
authors.forename: Sionagh
authors.initials: S
authors.lastname: Smith
authors.forename: Catherine
authors.initials: C
authors.lastname: Doherty
authors.forename: Gerry
authors.initials: G
authors.lastname: McLachlan
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000382:microbiology; D003550:Cystic Fibrosis / Q000150:complications; D004195:Disease Models, Animal; D011014:Pneumonia / Q000209:etiology* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000209:etiology* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa; D012756:Sheep