The impact of differential nutrient availability during acute lung injury on Pseudomonas aeruginosa growth

<bold>Introduction:</bold> Secondary bacterial pneumonia is a frequent complication of acute lung injury. Little is known about how altered nutrient availability in injured lungs contributes to pathogen growth. <bold>Aims and Objectives:</bold> To investigate the growth dynamics and nutrient uptake of Pseudomonas aeruginosa (Pa) in the injured lung microenvironment. <bold>Methods:</bold> Using a model of oxygen-induced lung injury, we obtained bronchoalveolar lavage fluid (BALF) from mice exposed to 95% FiO2 from 0 (healthy) to 96 h (injured). Acellular BALF was inoculated with Pa, bacterial growth was assessed via spectrophotometry, and BALF metabolomic profiles before and during Pa growth were acquired via 1H NMR spectroscopy. <bold>Results:</bold> Growth of Pa in BALF from injured murine lungs was enhanced relative to healthy lungs, and correlated with abundance of preferred metabolites. Maximum growth rate and total bacterial density were elevated for Pa grown in BALF from injured mice. Similarly, BALF from injured lungs initially contained increased concentrations of metabolites preferred by Pa (branched-chain amino acids, ketones), and these preferred metabolites decreased in concentration after 10 hours of bacterial growth. In contrast, glucose was used by Pa in healthy BALF only, suggesting that in healthy lungs, Pa relies on non-preferred metabolites due to low nutrient availability. <bold>Conclusions:</bold> Enhanced Pseudomonas aeruginosa growth in BALF from acutely injured lungs is attributable to increased availability of preferred bacterial nutrients. These findings support a model of secondary pneumonia in which the altered ecology of the alveolar microenvironment promotes selective bacterial outgrowth.