The influence ofinfection on the airway metabolome.

Abstract

is an environmentally resilient bacterium and an important cause of both acute and chronic infections in people with impaired natural barriers or immunological defences. Chronic respiratory infection withis a major cause of morbidity and mortality in people with airway diseases, including cystic fibrosis (CF) and non-CF bronchiectasis. Chronic airway infection is characterized by periods of relative stability punctuated by pulmonary exacerbations, during which times rapid bacterial outgrowth necessitates intense antimicrobial chemotherapy. The periods of stable infection can be modelled in mice by nasal instillation of airway-adaptedin saline, leading to prolonged colonization of both upper airway (sinus) and lower airway (lung) environments that is not associated with symptomatic disease. Here, we use NMR metabolomics to investigate the impact ofcolonization on the metabolic landscape of sinuses and lungs. Lung infection led to pronounced changes in the airway metabolome, with significant depletion of glucose and myo-inositol but enrichment of glutathione (GSH), relative to uninfected lungs. Changes in the sinuses were more subtle but could be identified through dimensionality reduction approaches. The NMR spectral peaks that discriminated between infected and uninfected sinuses in partial least squares discriminant analysis included those for lactate and choline but were mostly representative of yet unidentified metabolites. These data highlight the differential impact of infection on separate airway compartments and identify undefined metabolites undergoing pronounced abundance changes during infection.