Pseudomonas aeruginosa biological functions are inhibited by normal airway epithelial secretions: implications for cystic fibrosis (P3074)

Abstract

Abstract P. aeruginosa does not colonize healthy individuals, but it is the leading cause of death in patients with cystic fibrosis (CF). The ability of P. aeruginosa to readily colonize CF-lungs is at least partially related to alterations in airway secretions caused by the disease. In addition to being dehydrated, these secretions have reduced antimicrobial activity compared to that found in normal airways. Thus, we proposed that normal airway secretions contain one or more molecules that reduce P. aeruginosa virulence whereas CF airway secretions do not. To test this hypothesis in vitro, we collected apical secretions from polarized CFTR+ and CFTR- Calu-3 cell monolayers. We applied these secretions at various concentrations to the P. aeruginosa strain PA14 and examined the effect of the secretions on two key biological activities associated with P. aeruginosa virulence: motility and biofilm formation. Secretions from CFTR+ (“normal”) cells dose-dependently inhibited both PA14 flagellar motility and biofilm formation. However, secretions from CFTR- (“CF-like”) cells failed to inhibit either biological function. Our preliminary identification experiments suggest that the inhibitory agent(s) in the CFTR+ secretions is a heat-labile, large (>50 kDa) molecule, probably a protein. Thus, it is likely that normal epithelial secretions play a direct role in inhibiting P. aerugionsa virulence and that these secretions are dysfunctional in patients with CF.