Pseudomonas aeruginosa infection of respiratory epithelium in a cystic fibrosis xenograft model

Pulmonary infection with Pseudomonas aeruginosa in patients with cystic fib rosis (CF) causes a chronic destructive bronchitis. A xenograft model was u sed to study the susceptibility of the CF respiratory epithelium to P. aeru ginosa strain PAK and the virulence of certain mutants. Despite an early tr end toward increased susceptibility, colonization of CF xenografts (ID95, 6 2 colony-forming units [cfu]) was not statistically different (P = .5) than in xenografts with normal respiratory cells (ID95, 1.2 x 10(3) cfu). Infec tion severity in 12 CF xenografts (mean polymorphonuclear leukocyte [PMNL] density, 1.88 x 10(6) +/- 1.75 x 10(6)/xenograft) was similar to that in 16 non-CF xenografts (3.19 x 10(6) +/- 2.45 x 10(6) PMNL/xenograft), despite slightly greater bacterial density in the CF xenografts (mean, 1.57 +/- 2.7 3 x 10(6) cfu/xenograft) versus xenografts with normal epithelium (mean, 1. 03 +/- 1.3 x 10(6) cfu/xenograft). P. aeruginosa mutants pilA and fliF, but not rpoN, colonized normal respiratory xenografts, indicating that coloniz ation and infection in this model depend on an uncharacterized RpoN-control led gene. This model appears to be suitable for genetic study of P. aerugin osa virulence but not of the CF respiratory tract's unique susceptibility.