Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients

TLDR

Current CF pathogenesis theories predict distinct local environmental conditions and infection sites within the airways. The study proposes novel CF therapies that remove hypoxic mucus plaques and employ antibiotics effective against anaerobically adapted *Pseudomonas aeruginosa*. In vitro, increased epithelial O₂ consumption and mucus stasis in CF generate steep hypoxic gradients in thick mucus before infection. *P.

Abstract

Current theories of CF pathogenesis predict different predisposing “local environmental” conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Psuedomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O2 consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.