NMR-Metabolomics Shows That BolA Is an Important Modulator of Salmonella Typhimurium Metabolic Processes under Virulence Conditions

BolA is a ubiquitous global transcription factor. Despite its clear role in the induction of important stress-resistant physiological changes and its recent implication in the virulence of Salmonella, further research is required to shed light on the pathways modulated by BolA. In this study, we resorted to untargeted H-1-NMR metabolomics to understand the impact of BolA on the metabolic profile of Salmonella Typhimurium, under virulence conditions. Three strains of S. Typhimurium SL1344 were studied: An SL1344 strain transformed with an empty plasmid (control), a bolA knockout mutant (Delta bolA), and a strain overexpressing bolA (bolA(+)). These strains were grown in a minimal virulence-inducing medium and cells were collected at the end of the exponential and stationary phases. The extracts were analyzed by NMR, and multivariate and univariate statistical analysis were performed to identify significant alterations. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) of H-1-NMR data allowed the discrimination between the metabolic profiles of these strains, revealing increased levels of acetate, valine, alanine, NAD(+), succinate, coenzyme A, glutathione, and putrescine in bolA(+). These results indicate that BolA regulates pathways related to stress resistance and virulence, being an important modulator of the metabolic processes needed for S. Typhimurium infection.