Utilization of phosphatidylcholine, a lung surfactant component, as a major nurient source during Pseudomonas aeruginosa lung infection

Abstract

Pseudomonas aeruginosa can grow to high-cell-density (HCD) during infection of the cystic fibrosis (CF) lung. Phosphatidylcholine (PC), the major component of lung surfactant, has been hypothesized to support HCD growth of P. aeruginosa in vivo. Three different pathways, the betaine, glycerol and fatty acid degradation (Fad) pathways, are involved in the degradation of PC components including a phosphorylcholine headgroup, a glycerol molecule, and two long-chain fatty acids (FAs). The Fad pathway still remains largely uncharacterized in P. aeruginosa. During the course of this work, fadBA1,4,5 operons (3-hydroxyacyl-CoA dehydrogenase and acyl-CoA thiolase) were shown to be the most important operons involved in fatty acid degradation through mutational analysis. Various fad mutants and the triple pathway mutant were analyzed extensively by in vitro growth analysis, virulence characterization, and competition study. Defect of growth on PC as sole carbon source was most significant on the triple pathway mutants, as expected. This growth defect translated to in vivo competition disadvantage in BALB/c mice, suggesting the importance of PC as nutrient source in vivo.