ROLE OF MUTANT CFTR IN HYPERSUSCEPTIBILITY OF CYSTIC-FIBROSIS PATIENTS TO LUNG INFECTIONS

Cystic fibrosis (CF) patients are hypersusceptible to chronic Pseudomo nas aeruginosa lung infections. Cultured human airway epithelial cells expressing the Delta F508 allele of the cystic fibrosis transmembrane conductance regulator (CFTR) were defective in uptake of P. aeruginos a compared with cells expressing the wild-type allele. Pseudomonas aer uginosa lipopolysaccharide (LPS)-core oligosaccharide was identified a s the bacterial ligand for epithelial cell ingestion; exogenous oligos accharide inhibited bacterial ingestion in a neonatal mouse model, res ulting In Increased amounts of bacteria in the lungs. CFTR may contrib ute to a host-defense mechanism that is important for clearance of P. aeruginosa from the respiratory tract.