IMPAIRED ABILITY OF CFTR KNOCKOUT MICE TO CONTROL LUNG INFECTION WITHPSEUDOMONAS-AERUGINOSA

The present study was aimed at investigating the innate susceptibility of C57BL/6-Cftr(unc)/Cftr(unc) knockout [B6-Cftr(-/-)] mice to pulmon ary infection with Pseudomonas aeruginosa. Our results indicate that 5 8.4% of B6-Cftr(-/-) mice died within 6 d following lung infection wit h 10(5) P. aeruginosa entrapped in agar beads, whereas only 12.1% of B 6-Cftr (+/+) mice died over the same period of time. Moreover, the num ber of bacteria recovered from the lungs of B6-Cftr(-/-) mice 3 and 6 d after infection was significantly higher than that observed in their littermate controls. No correlation was found between the weight or a ge of the animals and the number of viable bacteria recovered from the lungs of mice. Histopathological examination of lung sections from P. aeruginosa-infected mice revealed that the infection results in a sev ere bronchopneumonia. Both B6-Cftr(-/-) knockout mice and their litter mate controls developed similar lung pathology during the course of in fection. Overall, results reported in the present study suggest that a defect at the Cftr locus leads to an exacerbation of P. aeruginosa lu ng infection resulting in a dramatically increased mortality rate and higher bacterial load.