Untargeted metabolomics reveals species-specific metabolite production and shared nutrient consumption by Pseudomonas aeruginosa and Staphylococcus aureus

While bacterial metabolism is known to impact antibiotic efficacy and virulence, the metabolic capacities of individual microbes in cystic fibrosis lung infections are difficult to disentangle from sputum samples. Here, we show that untargeted metabolomic profiling of supernatants of multiple strains of Pseudomonas aeruginosa and Staphylococcus aureus grown in monoculture in synthetic cystic fibrosis media (SCFM) reveal distinct species-specific metabolic signatures with limited strain-to-strain variability. The majority of metabolites significantly consumed by S. aureus were also consumed by P. aeruginosa, indicating that P. aeruginosa has the flexibility to metabolically outcompete S. aureus in coculture even in the absence of other pathogen-pathogen interactions. Finally, metabolites that were uniquely produced by one species or the other were identified. Specifically, the virulence factor precursor anthranilic acid as well as the quinoline 2,4-Quinolinediol (DHQ) were robustly produced across all tested strains of P. aeruginosa. Through the direct comparison of the extracellular metabolism of P. aeruginosa and S. aureus in a physiologically relevant environment, this work provides insight towards the potential metabolic interactions in vivo and supports the development of species-specific diagnostic markers of infection.