Co-culture metabolomics: a powerful tool for uncovering host-pathogen phenotypes driving Burkholderia infections.

Melioidosis, caused by the soil-dwelling pathogen Burkholderia pseudomallei (Bt), is a severe respiratory infection with limited treatment options. To investigate the host-pathogen metabolic interplay occurring during these intracellular infections, Hicks et al. built upon an in vitro co-culture model they developed with airway epithelial cells and Bt as a surrogate pathogen (D. J. Hicks, N. Aiosa, A. Sinha, O. A. Jaiyesimi, et al., mSystems 10:e00611-25, 2025, https://doi.org/10.1128/msystems.00611-25). Using an untargeted metabolomics approach tailored to central metabolism, they identified several host pathways that were altered during the Bt infection: polyamine biosynthesis, nicotinamide adenine dinucleotide salvage, and the tricarboxylic acid cycle. In addition, they found that several bacterial metabolites, including methylated nucleotide bases, peptidoglycan precursors, and amino acid derivatives, were altered due to Bt infection. These results show that co-culture metabolomics is an effective strategy for identifying host-pathogen metabolic phenotypes resulting from bacterial infections and can uncover new therapeutic strategies to combat melioidosis.