Chronic Pseudomonas aeruginosa infection reduces surfactant levels by inhibiting its biosynthesis.

摘要: Chronic Pseudomonas aeruginosa infection, as occurs in cystic fibrosis, is associated with decreased surfactant phospholipid levels. To investigate mechanisms, we measured synthesis of dipalmitoylphosphatidylcholine (DPPC), the major phospholipid. Mice received an agarose bead slurry alone, or were infected beads containing a clinical mucoid isolate P. aeruginosa. Bacterial infection after 3 days resulted approximately 50% reduction DPPC content versus control. These changes co-ordinate reductions mRNAs and immunoreactive levels for CTP: phosphocholine cytidylyltransferase (CCTalpha), rate-regulatory enzyme required synthesis. murine lung epithelia CCTalpha gene transcription without altering mRNA stability by mechanism other than release soluble extracellular inhibitor. Promoter deletional analysis revealed that activates negative response element from -1019 to -799 bp proximal 5'-flanking region. Exposure cells mutant strain producing alginate reduced promoter activity, whereas these effects not observed strains defective Murine type II isolated aeruginosa-infected promoter-beta-galactosidase transgenic mice exhibited significantly CCT beta-galactosidase activities Thus, reduces key biosynthetic thereby decreasing surfactant.