The influence of Pseudomonas aeruginosa infection on the airway metabolome

TY - JOUR

T1 - The influence of Pseudomonas aeruginosa infection on the airway metabolome

AU - Green, Angharad E.

AU - Ruhluel, Dilem

AU - Phelan, Marie

AU - Fothergill, Joanne L.

AU - Neill, Daniel R.

N1 - © 2025 The Authors

PY - 2025/10/8

Y1 - 2025/10/8

N2 - Pseudomonas aeruginosa 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 with P. aeruginosa is 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-adapted P. aeruginosa in 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 of P. aeruginosa colonization 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.

AB - Pseudomonas aeruginosa 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 with P. aeruginosa is 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-adapted P. aeruginosa in 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 of P. aeruginosa colonization 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.

KW - NMR

KW - Pseudomonas aeruginosa

KW - metabolomics

KW - respiratory infection

UR - https://www.scopus.com/pages/publications/105018275576

U2 - 10.1099/mic.0.001617

DO - 10.1099/mic.0.001617

M3 - Article

C2 - 41060828

SN - 1350-0872

VL - 171

JO - Microbiology (Reading, England)

JF - Microbiology (Reading, England)

IS - 10

M1 - 001617

ER -